Administration for treatment with anti-CD20 / anti-CD3 bispecific antibodies in elderly patients

Abstract

The present invention relates to the treatment of elderly subjects (e.g., subjects 65 years of age or older) having relapsed and / or refractory (R / R) non-Hodgkin lymphoma (NHL). More specifically, the present invention relates to the treatment of subjects having R / R NHL by intravenous administration of mosunetuzumab.

Description

Technical Field

[0001] Sequence Listing This application includes a Sequence Listing that was electronically submitted in ASCII format, the entire contents of which are incorporated herein by reference. The name of the ASCII copy created on May 31, 2022 is 50474-291WO1_Sequence_Listing_5_31_22_ST25, and the size is 23,618 bytes.

[0002] Field of the Invention The present invention relates to the treatment of B-cell proliferative disorders in elderly subjects. More specifically, the present invention relates to the administration of a bispecific antibody that binds to cluster of differentiation 20 (CD20) and cluster of differentiation 3 (CD3), such as an anti-CD20 / anti-CD3 bispecific antibody, such as mosunetuzumab, for the treatment of elderly subjects with relapsed and / or refractory (R / R) non-Hodgkin lymphoma (NHL; e.g., R / R follicular lymphoma (FL), and R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL)).

Background Art

[0003] Background Cancer is characterized by the uncontrolled growth of a subpopulation of cells. Cancer is the leading cause of death in developed countries and the second most common cause of death in developing countries, with over 14 million new cancer cases diagnosed and over 8 million cancer deaths occurring each year. Therefore, cancer care represents a significant and growing societal burden.

[0004] CD20-positive cell proliferative disorders such as B-cell proliferative disorders are a major cause of cancer-related death. For example, non-Hodgkin lymphoma (NHL) progresses rapidly and is fatal if untreated. In the United States, B-cell lymphoma constitutes approximately 80% to 85% of all cases of NHL. Follicular lymphoma (FL) is the most common indolent subtype of NHL, typically affecting older patients, with a median age at diagnosis of 65 years and occurring frequently in patients over 75 years of age (Castellino A, et al. Mediterr J Hematol Infect Dis 2017, 9: e2017009). Aggressive NHLs include DLBCL, transformed FL, and grade 3b FL. Up to 40% of DLBCL patients treated in first-line settings experience disease progression within 3 to 4 years (Friedberg JW. Hematology Am. Soc. Hematol Educ. Program. 2011, 2011: 498-505), and more than half of patients treated with second-line therapies do not achieve a complete remission (Gisselbrecht C et al. J. Clin. Oncol. 2010, 28: 4184-4190).

[0005] Bispecific antibodies (e.g., anti-CD20 / anti-CD3 bispecific antibodies, e.g., mosunetuzumab) can simultaneously bind to cell surface antigens on cytotoxic cells (e.g., via binding to T cells, cluster of differentiation 3 (CD3)) and cancer cells (e.g., via binding to B cells, CD20), and the bound cytotoxic cells destroy the juxtaposed bound cancer cells via an immunological synapse. However, the use of antibody-based immunotherapies such as these can be limited by unwanted effects, including cytokine-driven toxicity (e.g., cytokine release syndrome (CRS)), infusion-related reactions (IRR), severe tumor lysis syndrome (TLS), and central nervous system (CNS) toxicity. Furthermore, the introduction of monoclonal anti-CD20 antibodies such as rituximab has made it more difficult to find effective treatment options for the majority of patients previously exposed to anti-CD20 antibodies in treatment.

[0006] Older patients with FL (e.g., patients about 65 years of age or older) experience treatment-related difficulties more than younger patients due to increased comorbidities, reduced immune function, and access to fewer treatment options (Castellino A, et al. Mediterr J Hematol Infect Dis 2017;9:e2017009; Casulo C, et al. Blood Adv 2021;5:1737-1745). Accordingly, there is an unmet need in the art to develop effective methods of treating B cell proliferative disorders (e.g., non-Hodgkin lymphoma (NHL); e.g., follicular lymphoma (FL), transformed FL (trFL), or diffuse large B cell lymphoma (DLBCL)), particularly relapsed and / or refractory (R / R) NHL, FL, trFL, or DLBCL, to achieve a more favorable benefit-risk profile in older patients (e.g., patients about 65 years of age or older). SUMMARY OF THE INVENTION

[0007] SUMMARY OF THE INVENTION The present invention relates to a method of treating a subject (e.g., an older subject, e.g., a subject about 65 years of age or older) having relapsed and / or refractory (R / R) non-Hodgkin lymphoma (NHL) (e.g., R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B cell lymphoma (DLBCL)) by administration (e.g., intravenous administration) of an anti-CD20 / anti-CD3 bispecific antibody (e.g., mosunetuzumab).

[0008] The present invention is based in part on the discovery that an administration regimen comprising administering a bispecific antibody (e.g., mosunetuzumab) that binds to CD20 and CD3 over a plurality of dosing cycles (e.g., the first dosing cycle is a step-up fractionated dosing cycle) that includes a dose of a second dosing cycle (the "loading dose") that is greater than a relatively high third dose (C1D3) and / or a third dosing cycle (C3D1) and / or the dose of an additional dosing cycle (the "base dose") can effectively treat elderly subjects (e.g., subjects about 65 years of age or older) with B cell disorders while reducing toxicity (e.g., cytokine release syndrome and / or serious adverse events). The administration regimen of the present invention has also been found to be particularly effective in treating elderly subjects (e.g., subjects about 65 years of age or older).

[0009] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having relapsed or refractory (R / R) non-Hodgkin lymphoma (NHL; e.g., R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL)), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); and (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, or ± 3 mg; e.g., 30 mg).In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and C3D1 is 30 ± 6 mg.

[0010] In some embodiments, the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior lines of therapy. In some embodiments, the two or more prior lines of therapy include an anti-CD20 monoclonal antibody (e.g., rituximab), an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa), or both an anti-CD20 monoclonal antibody and an alkylating agent.

[0011] In some embodiments, the R / R NHL is R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL). In certain embodiments, the R / R NHL is R / R FL. In some embodiments, the FL is histologically demonstrated to be grade 1, 2, or 3a but not 3b according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90).

[0012] In some embodiments, the first dosing cycle, the second dosing cycle, and the third dosing cycle are each 21-day (±1 day) dosing cycles. In some embodiments, the method includes administering C1D1, C1D2, and C1D3 on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively. In some embodiments, the method includes administering C2D1 on day 1 of the second dosing cycle. In some embodiments, the method includes administering C3D1 on day 1 of the third dosing cycle.

[0013] In some embodiments, the dosing regimen further includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more) additional dosing cycles. In some embodiments, the dosing regimen includes 5 to 14 (5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) additional dosing cycles. In certain embodiments, the dosing regimen includes 5 additional dosing cycles. In another particular embodiment, the dosing regimen includes 14 additional dosing cycles. In some embodiments, each of the one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more) additional dosing cycles is a dosing cycle of 21 days (±1 day).

[0014] In some embodiments, each of the one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more) additional dosing cycles includes an additional single dose of mosunetuzumab. In some embodiments, the additional single dose of mosunetuzumab is administered to the subject on day 1 of each additional dosing cycle. In some embodiments, the additional single dose of mosunetuzumab is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, or ± 3 mg; e.g., 30 mg). In some embodiments, each additional dose of mosunetuzumab is 30 ± 6 mg.

[0015] In some embodiments, mosunetuzumab is administered by intravenous infusion.

[0016] In one aspect, the present invention provides a method of treating a population of subjects about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject according to a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ±0.2 mg, C1D2 is 2 ±0.4 mg, C1D3 is 60 ±12 mg, C2D1 is 60 ±12 mg, and C3D1 is 30 ±6 mg.

[0017] In one aspect, the present invention provides a method of treating a population of subjects about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C8D1 is 30 ± 6 mg.

[0018] In one aspect, the present invention provides a method of treating a population of subjects having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL) who are about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 17 twenty-one-day (±1 day) dosing cycles, wherein: (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, wherein C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1-C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, wherein each of C3D1-C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C17D1 is 30 ± 6 mg.

[0019] In some embodiments, the objective response rate in the target population is 65% or more (for example, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more; for example, 65 - 100%, 70 - 100%, 75 - 100%, 80 - 100%, 85 - 100%, 90 - 100%, 95 - 100%, 65 - 90%, 65 - 80%, 65 - 70%, 75 - 90%, 75 - 85%, 70 - 90%, or 80 - 90%; for example, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%). In some embodiments, the objective response rate in the target population is 75% or more. In some embodiments, the objective response rate in the target population is 85% or more. In some embodiments, the objective response rate in the target population is 90% or more.

[0020] In some embodiments, the complete response rate in the target population is 50% or more (for example, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more; for example, 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 50 - 90%, 50 - 80%, 50 - 70%, 50 - 60%, 50% - 75%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; for example, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%). In some embodiments, the complete response rate in the target population is 60% or more. In some embodiments, the complete response rate in the target population is 70% or more.

[0021] In some embodiments, more than 40% (e.g., more than 45%, more than 50%, more than 55%, more than 60%, more than 65%, more than 70%, more than 75%, more than 80%, more than 85%, more than 90%, or more than 95%; e.g., 40 - 100%, 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 40 - 90%, 40 - 80%, 40 - 70%, 40 - 60%, 40 - 50%, 50% - 70%, 50 - 60%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%) of the subjects with objective response maintained remission for 18 months. In some embodiments, more than 50% of the subjects with objective response maintained remission for 18 months.

[0022] In some embodiments, more than 50% (e.g., more than 55%, more than 60%, more than 65%, more than 70%, more than 75%, more than 80%, more than 85%, more than 90%, or more than 95%; e.g., 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 50 - 90%, 50 - 80%, 50 - 70%, 50 - 60%, 50% - 75%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%) of the subjects with complete response maintained complete remission for 18 months. In some embodiments, more than 60% of the subjects with complete response maintained complete remission for 18 months.

[0023] In some embodiments, the median duration of efficacy in the target population is 9 months or more (e.g., 9, 10, 11, 12, 13, 14, 15, 18, 21, 24, 27, 30, 33, 36 months or more; e.g., 9 - 12 months, 9 - 15 months, 9 - 18 months, 9 - 24 months, 12 - 18 months, 12 - 24 months, 12 - 36 months, 18 - 36 months, 24 - 36 months or more; e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months or more). In some embodiments, the median duration of efficacy in the target population is 15 months or more. In some embodiments, the median duration of efficacy in the target population is 18 months or more.

[0024] In some embodiments, the median duration of complete efficacy in the target population is 12 months or more (e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months or more; e.g., 12 - 15 months, 12 - 18 months, 12 - 21 months, 12 - 24 months, 12 - 30 months, 12 - 36 months, 15 - 18 months, 15 - 24 months, 18 - 24 months, 24 - 36 months, 18 - 36 months or more; e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months or more). In some embodiments, the median duration of complete efficacy in the target population is 16 months or more. In some embodiments, the median duration of complete efficacy in the target population is 18 months or more.

[0025] In some embodiments, more than 35% of the subjects (e.g., more than 40%, more than 45%, more than 50%, more than 55%, more than 60%, more than 65%, more than 70%, more than 75%, more than 80%, more than 85%, more than 90%, or more than 95%; e.g., 35 - 100%, 40 - 100%, 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 35 - 90%, 35 - 80%, 35 - 70%, 35 - 60%, 35 - 50%, 35 - 45%, 40 - 80%, 40 - 60%, 50% - 70%, 50 - 60%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%) have progression - free survival of 18 months. In some embodiments, more than 45% of the subjects have progression - free survival of 18 months.

[0026] In some embodiments, the median progression - free survival in the population of subjects is 12 months or more (e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months or more, or more than that; e.g., 12 - 15 months, 12 - 18 months, 12 - 21 months, 12 - 24 months, 12 - 30 months, 12 - 36 months, 15 - 18 months, 15 - 24 months, 18 - 24 months, 24 - 36 months, 18 - 36 months, or more than that; e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months, or more than that). In some embodiments, the median progression - free survival in the population of subjects is 17 months or more.

[0027] In some embodiments, the rate of serious adverse events excluding grade 5 malignant neoplasm progression in the population of interest is 45% or less (e.g., 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5% or less; e.g., 0 - 45%, 0 - 35%, 0 - 25%, 0 - 15%, 0 - 10%, 0 - 5%, 5 - 15%, 15 - 30%, 30 - 45%, 10 - 30%, 20 - 40%, 35 - 45%, 30 - 40%, 20 - 30%, or 10 - 20%; e.g., about 0%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40% or about 45%). In some embodiments, the rate of serious adverse events excluding grade 5 malignant neoplasm progression in the population of interest is 40% or less. In some embodiments, the rate of serious adverse events excluding grade 5 malignant neoplasm progression in the population of interest is 50% or less (e.g., about 50%, about 49%, about 48%, about 47%, or about 46%).

[0028] In some embodiments, the rate of serious adverse events related to mosunetuzumab in the population of interest is 40% or less (e.g., 35%, 30%, 25%, 20%, 15%, 10%, or 5% or less; e.g., 0 - 40%, 0 - 35%, 0 - 25%, 0 - 15%, 0 - 10%, 0 - 5%, 5 - 15%, 15 - 30%, 30 - 40%, 10 - 30%, 20 - 40%, 30 - 40%, 20 - 30%, or 10 - 20%; e.g., about 0%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35% or about 40%). In some embodiments, the rate of serious adverse events related to mosunetuzumab in the population of interest is 30% or less. In some embodiments, the rate of serious adverse events related to mosunetuzumab in the population of interest is 35% or less.

[0029] In some embodiments, the percentage of cytokine release syndrome of grade 3 or higher (as defined by the American Society for Transplantation and Cellular Therapy, 2018; ASTCT) in the population of interest is 5% or less (e.g., 4%, 3%, 2%, or 1% or less; e.g., 0 to 5%, 1 to 5%, 2 to 5%, 3 to 5%, 4 to 5%, 1 to 3%, 2 to 4%, or 0 to 3%; e.g., about 0%, about 1%, about 2%, about 3%, about 4%, or about 5%). In some embodiments, the percentage of cytokine release syndrome having a grade of 3 or higher (as defined by ASTCT) in the population of interest is 3% or less.

[0030] In some embodiments, the percentage of cytokine release syndrome of any grade (as defined by ASTCT) in the population of interest is 40% or less (e.g., 35%, 30%, 25%, 20%, 15%, 10%, or 5% or less; e.g., 0 to 40%, 0 to 35%, 0 to 25%, 0 to 15%, 0 to 10%, 0 to 5%, 5 to 15%, 15 to 30%, 25 to 40%, 10 to 30%, 20 to 40%, 25 to 35%, 35 to 40%, 30 to 40%, 20 to 30%, or 10 to 20%; e.g., about 0%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, or about 40%). In some embodiments, the percentage of cytokine release syndrome of any grade (as defined by ASTCT) in the population of interest is 30% or less. In some embodiments, the percentage of cytokine release syndrome of any grade (as defined by ASTCT) in the population of interest is 50% or less (e.g., 45% or less; e.g., 40 to 50%, 30 to 50%, 25 to 50%, 20 to 50%, 10 to 50%, 0 to 50%, 40 to 45%, 30 to 35%, 20 to 45%, 10 to 45%, 0 to 45%; e.g., about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50%).

[0031] In one aspect, the present invention provides a method of achieving objective response, complete response or progression-free survival in a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ±0.2 mg, C1D2 is 2 ±0.4 mg, C1D3 is 60 ±12 mg, C2D1 is 60 ±12 mg, and C3D1 is 30 ±6 mg.

[0032] In one aspect, the present invention provides a method of achieving objective response, complete response or progression-free survival in a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C8D1 is 30 ± 6 mg.

[0033] In one aspect, the present invention provides a method of achieving objective response, complete response or progression-free survival in a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 17 twenty-one day (±1 day) dosing cycles, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1-C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1-C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C17D1 is 30 ± 6 mg.

[0034] In some embodiments, the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior lines of therapy. In some embodiments, the two or more prior lines of therapy include an anti - CD20 monoclonal antibody (e.g., rituximab), an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa), or both an anti - CD20 monoclonal antibody and an alkylating agent.

[0035] In some embodiments, R / R NHL is R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B - cell lymphoma (DLBCL). In some embodiments, R / R NHL is R / R FL. In some embodiments, FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375 - 90), but not 3b.

[0036] In some embodiments, mosunetuzumab is administered by intravenous infusion.

[0037] In some embodiments, the subject achieves an objective efficacy. In some embodiments, the subject achieves a complete efficacy. In some embodiments, progression-free survival is maintained for 12 months or more (e.g., 12, 13, 14, 15, 18, 21, 24, 27, 30, 33, 36 months or more, or more than that; e.g., 12 - 15 months, 12 - 18 months, 12 - 21 months, 12 - 24 months, 12 - 30 months, 12 - 36 months, 15 - 18 months, 15 - 24 months, 18 - 24 months, 24 - 36 months, 18 - 36 months, or more than that; e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months, or more than that). In some embodiments, progression-free survival is maintained for 18 months or more.

[0038] In some embodiments, the method further comprises administering to the subject or each subject in a population of subjects one or more (e.g., 1, 2, 3, 4, 5, 6, or more than that) additional therapeutic agents.

[0039] In some embodiments, the one or more (e.g., 1, 2, 3, 4, 5, 6, or more than that) additional therapeutic agents comprise tocilizumab.

[0040] In some embodiments, one or more additional therapeutic agents (e.g., 1, 2, 3, 4, 5, 6, or more) include corticosteroids. In some embodiments, the corticosteroid includes dexamethasone or methylprednisolone. In some embodiments, the corticosteroid is administered to the subject or each subject in the population of subjects at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) prior to the administration of any dose of mosunetuzumab. In some embodiments, the corticosteroid is administered only during administration cycle 1 or administration cycle 2. In some embodiments, the corticosteroid is additionally administered during one or more subsequent administration cycles after administration cycle 2 (e.g., in administration cycles 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and / or 17). In some embodiments, the corticosteroid is administered intravenously. In some embodiments, the corticosteroid includes dexamethasone and is administered at a dose of about 20 mg (e.g., 20 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg or ± 2 mg; e.g., 20 mg). In some embodiments, the corticosteroid includes methylprednisolone and is administered at a dose of about 80 mg (e.g., 80 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 8 mg, ± 7 mg, or ± 8 mg; e.g., 80 mg).

[0041] In some embodiments, one or more additional therapeutic agents (e.g., 1, 2, 3, 4, 5, 6, or more) include antihistamines. In some embodiments, the antihistamine is administered to the subject or each subject in a population of subjects at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) prior to the administration of any dose of mosunetuzumab. In some embodiments, the antihistamine is administered only during administration cycle 1 or administration cycle 2. In some embodiments, the antihistamine is additionally administered during one or more subsequent administration cycles (e.g., in administration cycles 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and / or 17) after administration cycle 2. In some embodiments, the antihistamine is administered orally or intravenously. In some embodiments, the antihistamine includes diphenhydramine hydrochloride and is administered at a dose of about 50-100 mg (e.g., 50-90 mg, 50-80 mg, 50-70 mg, 50-60 mg, 60-100 mg, 70-100 mg, 80-100 mg, 90-100 mg, 70-80 mg, 60-90 mg, 60-80 mg, 70-90 mg, or 65-85 mg; e.g., about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, or about 100 mg).

[0042] In some embodiments, one or more additional therapeutic agents (e.g., 1, 2, 3, 4, 5, 6, or more) include an antipyretic. In some embodiments, the antipyretic is administered to the subject or each subject in a population of subjects at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) prior to administration of any dose of mosunetuzumab. In some embodiments, the antipyretic is administered only during administration cycle 1 or administration cycle 2. In some embodiments, the antipyretic is additionally administered during one or more subsequent administration cycles (e.g., in administration cycles 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and / or 17) after administration cycle 2. In some embodiments, the antipyretic is administered orally. In some embodiments, the antipyretic comprises acetaminophen and is administered in a dose of about 500 - 1000 mg (e.g., 500 - 900 mg, 500 - 800 mg, 500 - 700 mg, 500 - 600 mg, 600 - 1000 mg, 700 - 1000 mg, 800 - 1000 mg, 900 - 1000 mg, 700 - 800 mg, 600 - 900 mg, 600 - 800 mg, 700 - 900 mg, or 650 - 850 mg; e.g., about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg).

[0043] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ±0.2 mg, C1D2 is 2 ±0.4 mg, C1D3 is 60 ±12 mg, C2D1 is 60 ±12 mg, and C3D1 is 30 ±6 mg.

[0044] In one aspect, the present invention provides a method of treating a subject of about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1-C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1-C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C8D1 is 30 ± 6 mg.

[0045] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty-one day (±1 day) dosing cycles, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1-C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1-C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C17D1 is 30 ± 6 mg.

[0046] In one aspect, the present invention provides a method for treating a subject of about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of antihistamine is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and C3D1 is 30 ± 6 mg.

[0047] In one aspect, the present invention provides a method for treating a subject aged about 65 years or older (e.g., 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, 95 years or older, or 100 years or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more prior (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) treatment lines, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C8D1 is 30 ± 6 mg.

[0048] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty-one day (±1 day) dosing cycles, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1-C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1-C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior lines of treatment, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C17D1 is 30 ± 6 mg.

[0049] In some embodiments, (i) a single dose of corticosteroid is administered prior to administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle (e.g., prior to administration of C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, and / or C14D1 of mosunetuzumab); (ii) a single dose of antihistamine is administered prior to administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle (e.g., prior to administration of C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, and / or C14D1 of mosunetuzumab); and / or (iii) a single dose of antipyretic is administered prior to administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle (e.g., prior to administration of C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, and / or C14D1 of mosunetuzumab).

[0050] In some embodiments, (i) the corticosteroid is administered intravenously; (ii) the antihistamine is administered orally or intravenously; and / or (iii) the antipyretic is administered orally.

[0051] In some embodiments, (i) the corticosteroid comprises dexamethasone and is administered at a dose of about 20 mg (e.g., 20 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, or ± 2 mg; e.g., 20 mg), or the corticosteroid comprises methylprednisolone and is administered at a dose of about 80 mg (e.g., 80 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 8 mg, ± 7 mg, or ± 8 mg; e.g., 80 mg); (ii) the antihistamine comprises diphenhydramine hydrochloride and is administered at a dose of about 50 - 100 mg (e.g., 50 - 90 mg, 50 - 80 mg, 50 - 70 mg, 50 - 60 mg, 60 - 100 mg, 70 - 100 mg, 80 - 100 mg, 90 - 100 mg, 70 - 80 mg, 60 - 90 mg, 60 - 80 mg, 70 - 90 mg, or 65 - 85 mg; e.g., about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, or about 100 mg); and / or (iii) the antipyretic comprises acetaminophen and is administered at a dose of about 500 - 1000 mg (e.g., 500 - 900 mg, 500 - 800 mg, 500 - 700 mg, 500 - 600 mg, 600 - 1000 mg, 700 - 1000 mg, 800 - 1000 mg, 900 - 1000 mg, 700 - 800 mg, 600 - 900 mg, 600 - 800 mg, 700 - 900 mg, or 650 - 850 mg; e.g., about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg).

[0052] In some embodiments, the subject described herein is a human subject. BRIEF DESCRIPTION OF THE DRAWINGS

[0053]

Figure 1

Mode for Carrying Out the Invention

[0054] Detailed Description The present invention relates to a method of treating an elderly subject (i.e., about 65 years of age or older) or a population of elderly subjects (i.e., each about 65 years of age or older) having relapsed and / or refractory (R / R) non-Hodgkin lymphoma (NHL; e.g., diffuse large B-cell lymphoma (DLBCL; e.g., Richter transformation), follicular lymphoma (FL; e.g., grade 1 FL, grade 2 FL, grade 3 FL (e.g., grade 3a FL, or grade 3b FL) or transformed FL (trFL); e.g., R / R NHL, R / R DLBCL, R / R FL or R / R trFL) by intravenously administering (e.g., via intravenous infusion) an anti-CD20 / anti-CD3 bispecific antibody (e.g., mosunetuzumab) to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle. In some cases, the first dosing cycle comprises a first dose (C1D1), a second dose (C1D2) and a third dose (C1D3) of mosunetuzumab, C1D1 is from about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg. In some cases, the second dosing cycle comprises a single dose (C2D1) of about 60 mg of mosunetuzumab. In some cases, the third dosing cycle comprises a single dose (C3D1) of about 30 mg of mosunetuzumab.

[0055] As described above, the present invention is based in part on the discovery that an administration regimen comprising administration of mosunetuzumab over a plurality of administration cycles (e.g., the first administration cycle is a step-up fractionated administration cycle) that includes a dose of a second administration cycle (C2D1) in an amount greater than that of a relatively high third dose (C1D3) and / or a third administration cycle (C3D1) and / or a dose of an additional administration cycle can effectively treat subjects with R / R NHL (e.g., R / R FL, R / R DLBCL or R / R trFL) while reducing toxicity (e.g., severe adverse events and / or cytokine release syndrome). Further, the present invention is based in part on the finding that the administration regimens disclosed herein are particularly effective in elderly subjects (i.e., subjects about 65 years of age or older) as compared to, for example, non-elderly subjects (i.e., subjects about 64 years of age or younger, e.g., subjects about 18 to 64 years of age).

[0056] I. General Technology The techniques and procedures described or referenced in this specification are generally well understood and commonly employed by those skilled in the art using conventional methodologies, such as the widely utilized methodologies described below: Sambrook et al., Molecular Cloning: A Laboratory Manual 3d edition (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.; Current Protocols in Molecular Biology (F.M. Ausubel, et al., eds., (2003)); the series Methods in Enzymology (Academic Press, Inc.): PCR 2: A Practical Approach (M.J. MacPherson, B.D. Hames and G.R. Taylor eds. (1995)), Harlow and Lane, eds. (1988) Antibodies, A Laboratory Manual, and Animal Cell Culture (R.I. Freshney, ed. (1987)); Oligonucleotide Synthesis (M.J. Gait, ed., 1984); Methods in Molecular Biology, Humana Press; Cell Biology: A Laboratory Notebook (J.E. Cellis, ed., 1998) Academic Press; Animal Cell Culture (R.I. Freshney), ed., 1987); Introduction to Cell and Tissue Culture (J.P. Mather and P.E.R. Roberts, 1998) Plenum Press; Cell and Tissue Culture: Laboratory Procedures (A. Doyle, J.B. Griffiths, and D.G. Newell, eds., 1993 - 8) J.Wiley and Sons; Handbook of Experimental Immunology (D.M. Weir and C.C. Blackwell, eds.); Gene Transfer Vectors for Mammalian Cells (J.M. Miller and M.P. Calos, eds., 1987); PCR: The Polymerase Chain Reaction, (Mullis et al., eds., 1994); Current Protocols in Immunology (J.E. Coligan et al., eds., 1991); Short Protocols in Molecular Biology (Wiley and Sons, 1999); Immunobiology (C.A. Janeway and P. Travers, 1997); Antibodies (P. Finch, 1997); Antibodies: A Practical Approach (D. Catty., ed., IRL Press, 1988 - 1989); Monoclonal Antibodies: A Practical Approach (P. Shepherd and C. Dean, eds., Oxford University Press, 2000); Using Antibodies: A Laboratory Manual (E. Harlow and D. Lane (Cold Spring Harbor Laboratory Press, 1999); The Antibodies (M. Zanetti and J.D. Capra, eds., Harwood Academic Publishers, 1995); and Cancer: Principles and Practice of Oncology (V.T. DeVita et al., eds., J.B. Lippincott Company, 1993).

[0057] II. Definitions It is understood that the aspects and embodiments of the invention described herein include those "comprising", "consisting of", and "consisting essentially of" the aspects and embodiments.

[0058] As used herein, the singular forms "a", "an", and "the" include the plural unless otherwise indicated.

[0059] As used herein, the term "about" refers to the normal error range of each value, which can be easily understood by those skilled in the art of this technology. References to values or parameters with "about" in this specification include (and describe) embodiments directed to the value or parameter itself. In some embodiments, the term "about" value or parameter refers to the value or parameter ±10%. In certain embodiments, when referring to the age of a subject or individual, the term "about" refers to the range from that age to age + 1 (i.e., a 65-year-old subject is "about 65 years old" up to 66 years old).

[0060] "Disorder" includes any symptom that will benefit from treatment, including but not limited to chronic and acute disorders or diseases, including the pathological symptoms that cause a mammal to suffer from the disorder in question.

[0061] The terms "cell proliferative disorder" and "proliferative disorder" refer to disorders associated with some degree of abnormal cell proliferation. In one embodiment, the cell proliferative disorder is cancer. In another embodiment, the cell proliferative disorder is a tumor.

[0062] The terms "cancer" and "cancerous" refer to or describe physiological conditions in mammals typically characterized by uncontrolled cell growth. Examples of cancer include, but are not limited to, blood cancers such as mature B cell cancers including non-Hodgkin lymphoma (NHL), excluding Hodgkin lymphoma, such as diffuse large B cell lymphoma (DLBCL), which can be relapsed and / or refractory DLBCL or Richter transformation. Also, other specific examples of cancer include germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL), activated B cell-like (ABC) DLBCL, follicular lymphoma (FL), transformed FL, mantle cell lymphoma (MCL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), marginal zone lymphoma (MZL), transformed MZL, high-grade B cell lymphoma, primary mediastinal (thymic) large B cell lymphoma (PMLBCL), small lymphocytic leukemia (SLL), lymphoplasmacytic lymphoma (LL), transformed LL, Waldenström macroglobulinemia (WM), central nervous system lymphoma (CNSL), Burkitt lymphoma (BL), B cell prolymphocytic leukemia, splenic marginal zone lymphoma, hairy cell leukemia, splenic lymphoma / leukemia, unclassifiable, splenic diffuse red pulp small B cell lymphoma, hairy cell leukemia variant, heavy chain disease, alpha heavy chain disease, gamma heavy chain disease, mu heavy chain disease, multiple myeloma, solitary plasmacytoma of bone, extramedullary plasmacytoma, extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), nodal marginal zone lymphoma, pediatric nodal marginal zone lymphoma, pediatric follicular lymphoma, primary cutaneous follicle center lymphoma, T cell / histiocyte-rich large B cell lymphoma, primary CNS DLBCL, primary cutaneous DLBCL, leg type, elderly EBV-positive DLBCL, DLBCL associated with chronic inflammation, lymphomatoid granulomatosis, intravascular large B cell lymphoma, ALK-positive large B cell lymphoma, plasmablastic lymphoma, large B cell lymphoma arising from HHV8-associated multicentric Castleman disease, primary effusion lymphoma: an unclassifiable B cell lymphoma with intermediate features between DLBCL and Burkitt lymphoma, and an unclassifiable B cell lymphoma with intermediate features between DLBCL and classical Hodgkin lymphoma, among others.Furthermore, examples of cancers include, but are not limited to, carcinomas, lymphomas, blastomas, sarcomas, and lymphoid malignancies including leukemia or B-cell lymphoma. Further specific examples of such cancers include multiple myeloma (MM); low-grade / follicular NHL; small lymphocytic (SL) NHL; intermediate-grade / follicular NHL; intermediate-grade diffuse NHL; high-grade immunoblastic NHL; high-grade lymphocytic NHL; high-grade small non-cleaved cell NHL; large disease NHL; AIDS-related lymphoma; and acute lymphocytic leukemia (ALL); chronic myelogenous leukemia; and post-transplant lymphoproliferative disorder (PTLD), but are not limited thereto. In certain embodiments, the cancer is NHL. In some embodiments, the NHL is relapsed and / or refractory (R / R). In some embodiments, the R / R NHL is R / R FL, R / R DLBCL or R / R transformed FL (trFL). In certain embodiments, the R / R NHL is R / R FL (e.g., R / R FL that is grade 1, 2 or 3a but not 3b according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90)).

[0063] "Tumor", as used herein, refers to the growth and proliferation of all neoplastic cells, whether malignant or benign, and all pre-cancerous and cancerous cells and tissues. The terms "cancer", "cancerous", "cell proliferative disorder", "proliferative disorder", and "tumor" are not mutually exclusive as referred to herein.

[0064] The term "B-cell proliferative disorder" or "B-cell malignancy" refers to disorders associated with somewhat abnormal B-cell proliferation, including, for example, lymphoma, leukemia, myeloma, and myelodysplastic syndromes. In some cases, B-cell proliferative disorders are lymphomas such as non-Hodgkin lymphoma (NHL), including, for example, follicular lymphoma (FL) (e.g., relapsed and / or refractory FL or transformed FL (trFL)), diffuse large B-cell lymphoma (DLBCL) (e.g., relapsed and / or refractory DLBCL or Richter transformation), mantle cell lymphoma (MCL), high-grade B-cell lymphoma (HGBL), primary mediastinal (thymic) large B-cell lymphoma (PMLBCL), diffuse B-cell lymphoma, small lymphocytic lymphoma, marginal zone lymphoma (MZL), Burkitt lymphoma, or lymphoplasmacytic lymphoma. In another embodiment, the B-cell proliferative disorder is a leukemia such as chronic lymphocytic leukemia (CLL). In some embodiments, the B-cell proliferative disorder (e.g., NHL) is relapsed and / or refractory (R / R). In some embodiments, the R / R B-cell proliferative disorder (e.g., NHL) is R / R FL, R / R transformed trFL, or R / R DLBCL. In certain embodiments, the B-cell proliferative disorder is R / R FL (e.g., R / R FL that is grade 1, 2, or 3a but not 3b according to the World Health Organization classification of lymphoid neoplasms (referenced in Swerdlow SH, et al. Blood 2016;127:2375-90)). In some embodiments, R / R FL is R / R to at least two prior treatment lines.

[0065] "Refractory disease" is defined as having no complete remission to at least first-line therapy. In one embodiment, refractory disease is defined as having no response to prior treatment or recurrence within 6 months of a preceding treatment. In one embodiment, refractory disease is characterized by progressive disease (PD) as the best response to first-line therapy, stable disease (SD) as the best response after at least one first-line therapy, or partial response (PR) as the best response, and one or more of residual disease or disease progression demonstrated by biopsy after partial response. "Recurrent disease" is defined as complete remission to first-line therapy. In one embodiment, recurrence of the disease is demonstrated by biopsy. In one embodiment, the subject has recurred or been non-responsive after at least one preceding systemic treatment regimen or line of therapy. In some embodiments, at least one of the preceding lines of therapy includes an anti-CD20 antibody (e.g., rituximab) and / or an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa).

[0066] As used herein, "treatment" (and its grammatical variations such as "treat" or "treating") refers to a clinical intervention in an attempt to alter the natural course of a subject being treated and can be performed for prophylaxis or during the course of clinical pathology. Desired effects of treatment include, but are not limited to, preventing recurrence of a disease (e.g., R / R NHL, e.g., R / R FL, R / R trFL, or R / R DLBCL), alleviating symptoms, attenuating any direct or indirect pathological consequence of the disease, preventing metastasis, decreasing the rate of disease progression, improving or alleviating the medical condition, and improving remission or prognosis. In some embodiments, the antibodies and antibody-drug conjugates of the invention are used to delay the onset or progression of a disease.

[0067] "Delaying the progression" of a disorder or disease means postponing, hindering, decelerating, retarding, stabilizing, and / or delaying the development of a disease or disorder (e.g., R / R NHL, e.g., R / R FL, R / R trFL, or R / R DLBCL). This delay can be of various durations depending on the disease history and / or the individual being treated. As will be apparent to those skilled in the art, a sufficient or significant delay can, in effect, encompass prevention in the sense that the individual does not develop the disease. For example, it is possible to delay advanced cancer such as the occurrence of metastases.

[0068] "To reduce" or "to inhibit" means, for example, the ability to cause an overall decrease of 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95% or more. For clarity, this term also includes reduction to 0 (or below the detection limit of the assay method), i.e., complete disappearance or elimination. In certain embodiments, the reduction or inhibition is cytokine-driven toxicity (e.g., cytokine release syndrome (CRS)), infusion-related reaction (IRR), macrophage activation syndrome (MAS), neurotoxicity, severe tumor lysis syndrome (TLS), neutropenia, thrombocytopenia, elevated liver enzymes, and / or central nervous system (CNS) toxicity, etc. after treatment with mosunetuzumab using the step-up dosing regimen of the present invention compared to a preset administration that does not change with the target dose of mosunetuzumab. In other embodiments, "to reduce" or "to inhibit" can refer to the effector functions of the antibody mediated by the antibody Fc region, and such effector functions specifically include complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cell phagocytosis (ADCP). In other embodiments, the reduction or inhibition can refer to the symptoms, presence or size of metastases, or size of the primary tumor of the treated R / R NHL (e.g., R / R FL (e.g., R / R FL, e.g., grade 1, 2 or 3a but not 3b R / R FL), R / R trFL or R / R DLBCL). In yet other embodiments, reducing or inhibiting cancer recurrence means reducing or inhibiting tumor or cancer recurrence, or tumor or cancer progression.

[0069] "Administering" means a method of giving a dosage of a compound (e.g., a bispecific antibody, e.g., mosunetuzumab) or a composition (e.g., a pharmaceutical composition, e.g., a pharmaceutical composition containing a bispecific antibody, e.g., a composition or pharmaceutical composition containing mosunetuzumab) to a subject. The compounds and / or compositions (e.g., compounds and / or compositions containing mosunetuzumab) utilized in the methods described herein can be administered intravenously (e.g., by intravenous infusion).

[0070] As used herein, a "fixed" or "flat" dose of a therapeutic agent (e.g., a bispecific antibody, e.g., mosunetuzumab) refers to a dose that is administered to a subject regardless of the subject's body weight or body surface area (BSA). Thus, this fixed or constant dose is provided as an absolute amount of the therapeutic agent (e.g., mg), rather than as a mg / kg dose or mg / m 2 dose, and rather as an absolute amount of the therapeutic agent (e.g., mg).

[0071] A "subject" or "individual" is a mammal. Mammals include, but are not limited to, primates (e.g., non-human primates such as humans and monkeys), domestic animals (e.g., cows, sheep, cats, dogs, and horses), rabbits, and rodents (e.g., mice and rats). In certain embodiments, the subject or individual is a human. In some embodiments, the subject is a patient.

[0072] As used herein, a "reference population", e.g., "reference population of subjects", refers to a population (e.g., a population of subjects) used for comparison purposes. In some embodiments, the reference population of subjects includes subjects having R / R NHL (e.g., R / R FL, R / R trFL, or R / R DLBCL), and / or subjects who have relapsed after at least two prior lines of therapy and / or are refractory (R / R), including when at least one prior line of therapy included an anti-CD20 antibody and / or an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa). In some embodiments, each subject in the reference population of subjects is less than about 65 years old. Further, one of ordinary skill in the art will understand "reference population" in the context of the comparison being made. For example, in some embodiments, the reference population is a population of subjects less than about 65 years old, and a dosing regimen comprising mosunetuzumab is administered to the same extent as to a subject or population of subjects greater than or equal to about 65 years old who receive a dosing regimen comprising mosunetuzumab.

[0073] "Individual efficacy" or "efficacy" includes, but is not limited to, (1) some degree of inhibition, including deceleration and complete cessation, of disease progression (e.g., progression of NHL (e.g., FL, e.g., R / R FL, e.g., R / R FL that is grade 1, 2, or 3a but not 3b according to the World Health Organization classification of lymphoid neoplasms (referenced in Swerdlow SH, et al. Blood 2016;127:2375-90)); (2) reduction in tumor size; (3) inhibition of cancer cell infiltration into adjacent peripheral organs and / or tissues (i.e., reduction, deceleration, or complete cessation); (4) inhibition of metastasis (i.e., reduction, deceleration, or complete cessation); (5) some degree of alleviation of one or more symptoms associated with NHL (e.g., FL, e.g., R / R FL); (6) increase or prolongation of survival duration, including overall survival and progression-free survival; and / or (7) decrease in mortality at a given time point after treatment, and can be evaluated using any evaluation item that indicates a benefit to the subject.

[0074] As used herein, "complete response" or "CR" refers to the disappearance of all target lesions (i.e., all evidence of the disease). In some embodiments, the "complete response rate" of a population of subjects is the proportion of subjects in the population that have a complete response.

[0075] As used herein, "partial response" or "PR" refers to at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions with reference to the baseline SLD, or at least a 50% decrease in the product of the diameters (SPD) of target lesions with reference to the baseline SPD. In some embodiments, the "partial response rate" of a population of subjects is the proportion of subjects in the population that have a partial response.

[0076] As used herein, "objective response rate" (ORR) means the sum of the complete response (CR) rate and the partial response (PR) rate.

[0077] As used herein, the "duration of objective response" or "duration of response" (DOR) is defined as the time from the first occurrence of a recorded objective response (e.g., partial or complete response) until the earlier of the occurrence of recorded disease progression or death from any cause.

[0078] As used herein, the "duration of complete response" (DoCR) is defined as the time from the first occurrence of a recorded complete response until the earlier of the occurrence of recorded disease progression or death from any cause.

[0079] "Sustained response" refers to a continuing effect on reducing tumor growth after treatment interruption. For example, the tumor size can remain the same or become smaller compared to its size at the start of the dosing phase. In some embodiments, the sustained response has a duration that is at least the same as the treatment period, at least 1.5 times, 2.0 times, 2.5 times, or 3.0 times the treatment period.

[0080] "Effective response" or "responsiveness" of a subject to treatment with a medicament and similar terms refer to the clinical or therapeutic benefit conferred on a subject at risk of or suffering from a disease or disorder such as cancer. In one embodiment, such benefits include any one or more of prolonging the survival period (including overall survival and progression-free survival), resulting in an objective response (including complete or partial response), or improving the signs or symptoms of cancer.

[0081] A subject who "does not show an effective response" to treatment refers to a subject who has none of the following: an extended survival period (including overall survival and progression-free survival); an objective response (including complete or partial response); or improved signs or symptoms of cancer.

[0082] As used herein, "survival" refers to a subject who remains alive, including overall survival and progression-free survival.

[0083] As used herein, "overall survival" (OS) refers to the proportion of subjects in a group who are alive at a specified time period, e.g., one or five years after diagnosis or treatment.

[0084] As used herein, "progression-free survival" (PFS) refers to the length of time during and after treatment that the treated disease (e.g., NHL, e.g., FL (e.g., R / R FL, e.g., grade 1, 2, or 3a but not 3b R / R FL), R / R trFL, or R / R DLBCL) does not worsen. Progression-free survival can include the amount of time the subject experiences a complete or partial response, as well as the amount of time the subject experiences stable disease.

[0085] As used herein, "stable disease" or "SD" refers to the absence of sufficient shrinkage of target lesions to be considered a PR or sufficient increase to be considered a PD, based on the minimum SLD since the start of treatment.

[0086] As used herein, "progressive disease" or "PD" refers to an increase of at least 20% in the SLD of target lesions based on the minimum SLD recorded since the start of treatment, or an increase of at least 50% in the SPD of target lesions based on the minimum SPD, or the presence of one or more new lesions.

[0087] As used herein, "delaying the progression of" a disorder or disease means deferring, preventing, decelerating, retarding, stabilizing, and / or delaying the development of a disease or disorder (e.g., NHL, e.g., FL (e.g., R / R FL, e.g., grade 1, 2, or 3a but not 3b R / R FL), R / R trFL, or R / R DLBCL). This delay can be of various durations depending on the disease history and / or the subject being treated. As will be apparent to those skilled in the art, a sufficient or significant delay can effectively encompass prevention in that the subject does not develop the disease. For example, in advanced cancer, the development of central nervous system (CNS) metastases can be delayed.

[0088] As used herein, the term "reducing or inhibiting cancer recurrence" means reducing or inhibiting the recurrence of a tumor or cancer, or the progression of a tumor or cancer.

[0089] "Prolonging survival" means prolonging the overall survival or progression-free survival of a treated subject compared to an untreated subject (e.g., a subject not treated with a medicament), or compared to a subject not expressing a specified level of biomarker, and / or compared to a subject treated with an approved anti-tumor agent. Objective response refers to a measurable response including complete response (CR) or partial response (PR).

[0090] The term "antibody" is used herein in the broadest sense and encompasses various antibody structures including, but not limited to, monoclonal antibodies, polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired antigen-binding activity.

[0091] "Antibody fragment" refers to a molecule other than an intact antibody that comprises a portion of an intact antibody that binds an antigen to which the intact antibody binds. Examples of antibody fragments include, but are not limited to, Fv, Fab, Fab’, Fab’-SH, F(ab’)2, diabody, linear antibodies, single-chain antibody molecules (e.g., scFv); and multispecific antibodies formed from antibody fragments.

[0092] The terms "full-length antibody", "intact antibody", and "whole antibody" are used interchangeably herein to refer to an antibody having a structure substantially the same as a native antibody structure or having a heavy chain that contains an Fc region as defined herein.

[0093] The term "cluster of differentiation 3" or "CD3", as used herein, unless otherwise indicated, refers to any native CD3 from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats), and includes, for example, the CD3ε, CD3γ, CD3α, and CD3β chains. This term encompasses "full-length" unprocessed CD3 (e.g., unprocessed or unmodified CD3ε or CD3γ), as well as any form of CD3 resulting from intracellular processing. This term also encompasses naturally occurring variants of CD3, including, for example, splice variants or allelic variants. CD3 includes, for example, the human CD3ε protein that is 207 amino acids in length (NCBI reference sequence number NP_000724), and the human CD3γ protein that is 182 amino acids in length (NCBI reference sequence number NP_000064).

[0094] As used herein, the term "rituximab" or "RITUXAN®" refers to an anti-CD20 antibody (e.g., an anti-CD20 monoclonal antibody) having the Proposed International Nonproprietary Names for Pharmaceutical Substances (Proposed INN) List 77 (WHO Drug Information, Vol. 11, No. 2, 1997, p. 99) or CAS registration number 174722-31-7.

[0095] As used herein, the terms "obinutuzumab" or "GAZYVA®" refer to an anti-CD20 antibody (e.g., an anti-CD20 monoclonal antibody) having the Proposed International Nonproprietary Name for Pharmaceutical Substances (Proposed INN) List 99 (WHO Drug Information, Vol. 22, No. 2, 2008, p. 396), the Proposed International Nonproprietary Name for Pharmaceutical Substances (Proposed INN) List 108 (WHO Drug Information, Vol. 26, No. 4, 2012, p. 453), or the CAS Registry Number 949142-50-1.

[0096] As used herein, the terms "cluster of differentiation 20" or "CD20" refer to any native CD20 derived from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats), unless otherwise indicated. This term encompasses "full-length", unprocessed CD20, and any form of CD20 resulting from intracellular processing. This term also encompasses naturally occurring variants of CD20, including, for example, splice variants or allelic variants. CD20 includes, for example, the human CD20 protein (e.g., NCBI Reference Sequence Numbers NP_068769.2 and NP_690605.1, see), which can be produced, for example, from a variant mRNA transcript that is 297 amino acids in length and lacks a portion of the 5'UTR (e.g., NCBI Reference Sequence Number NM_021950.3, see), or a longer variant mRNA transcript (e.g., NCBI Reference Sequence Number NM_152866.2, see).

[0097] The terms "anti-CD20 / anti-CD3 bispecific antibody", "bispecific anti-CD20 / anti-CD3 antibody", and "antibody that binds to CD20 and CD3", or variants thereof, refer to mosunetuzumab.

[0098] As used herein, the term "mosunetuzumab" refers to an anti-CD20 / anti-CD3 bispecific antibody having the International Nonproprietary Name (INN) listed in List 117 of the World Health Organization (WHO Drug Information, Vol. 31, No. 2, 2017, pp. 304-305) or the CAS registration number 1905409-39-3.

[0099] As used herein, the terms "binds", "specifically binds to", or "is specific for" refer to a measurable and reproducible interaction, such as the binding between a target and an antibody, which determines the presence of the target in the presence of a heterogeneous population of molecules, including biomolecules. For example, an antibody that specifically binds to a target (which may be an epitope) binds to this target with a higher affinity, binding strength, more readily, and / or for a longer duration than it binds to other targets. In one embodiment, the degree to which the antibody binds to an irrelevant target is about 10% or less of the binding of the antibody to the target as measured by radioimmunoassay (RIA). In certain embodiments, an antibody that specifically binds to a target has a dissociation constant (K D ) of 1 μM or less, 100 nM or less, 10 nM or less, 1 nM or less, or 0.1 nM or less. In certain embodiments, the antibody specifically binds to an epitope on a protein that is conserved between proteins from different species. In another embodiment, specific binding can include, but is not necessarily, exclusive binding. The terms used herein are, for example, 10 -4 M or less, or 10 -5 M or less, or 10 -6 M or less, or 10 -7 M or less, or 10 -8 M or less, or 10 -9 M or less, or 10 -10 M or less, or 10 -11 M or less, or 10 -12 M or less for the K D to a target, or 10 -4 M to 10 -6 M or 10 -6 M to 10-10 M or 10 -7 M to 10 -9 K within the range of M D can be represented by a molecule having. As will be understood by those skilled in the art, affinity and K D values are inversely correlated. High affinity for an antigen is measured by a low K D value. In one embodiment, the term "specific binding" refers to binding when a molecule binds to a particular polypeptide or epitope on a particular polypeptide without substantially binding to any other polypeptide or polypeptide epitope.

[0100] The term "pharmaceutical preparation" refers to a preparation that is in a form such that the biological activity of the active ingredient contained therein is effective and that does not contain additional ingredients that are unacceptably toxic to the subject to which the preparation is administered.

[0101] "Pharmaceutically acceptable carrier" refers to components in a pharmaceutical preparation other than the active ingredient that are non-toxic to the subject. Pharmaceutically acceptable carriers include, but are not limited to, buffers, additives, stabilizers, or preservatives.

[0102] As used herein, the term "chemotherapeutic agent" refers to compounds useful in the treatment of cancers such as NHL, e.g., (FL, e.g., R / R FL, e.g., R / R FL that is grade 1, 2 or 3a but not 3b, R / R trFL or R / R DLBCL). Examples of chemotherapeutic agents include the following: EGFR inhibitors (small molecule inhibitors (e.g., erlotinib (TARCEVA®, Genentech / OSI Pharm.); PD 183805 (CI 1033, 2-propenamide, N-[4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-quinazolinyl]-, dihydrochloride, Pfizer Inc.); ZD1839, gefitinib (IRESSA®) 4-(3'-chloro-4'-fluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline, AstraZeneca); ZM 105180 ((6-amino-4-(3-methylphenyl-amino)-quinazoline, Zeneca); BIBX-1382 (N8-(3-chloro-4-fluoro-phenyl)-N2-(1-methyl-piperidin-4-yl)-pyrimido[5,4-d]pyrimidine-2,8-diamine, Boehringer Ingelheim); PKI-166 ((R)-4-[4-[(1-phenylethyl)amino]-1H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenyl); (R)-6-(4-hydroxyphenyl)-4-[(1-phenylethyl)amino]-7H-pyrrolo[2,3-d]pyrimidine); CL-387785 (N-[4-[(3-bromophenyl)amino]-6-quinazolinyl]-2-butynamide); EKB-569 (N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxy-6-quinolinyl]-4-(dimethylamino)-2-butenamide) (Wyeth); AG1478 (Pfizer); AG1571 (SU 5271; Pfizer); and dual EGFR / HER2 tyrosine kinase inhibitors, e.g., lapatinib (TYKERB®, GSK572016 or N-[3-chloro-4-[(3fluorophenyl)methoxy]phenyl]-6[5[[[2methylsulfonyl)ethyl]amino]methyl]-2-furanyl]-4-quinazolineamine));Tyrosine kinase inhibitors (e.g., EGFR inhibitors; small molecule HER2 tyrosine kinase inhibitors, e.g., TAK165 (Takeda); CP-724,714, an oral selective inhibitor of the ErbB2 receptor tyrosine kinase (Pfizer and OSI); dual HER inhibitors, e.g., EKB-569, which preferentially binds to EGFR but inhibits both EGFR- and HER2-overexpressing cells (available from Wyeth); PKI-166 (Novartis); pan-HER inhibitors, e.g., canertinib (CI-1033; Pharmacia); Raf-1 inhibitors, e.g., the antisense agent ISIS-5132 that inhibits Raf-1 signaling (ISIS Pharmaceuticals); non-HER-targeted tyrosine kinase inhibitors, e.g., imatinib mesylate (GLEEVEC®, Glaxo SmithKline); multi-targeted tyrosine kinase inhibitors, e.g., sunitinib (SUTENT®, Pfizer); VEGF receptor tyrosine kinase inhibitors, e.g., batatinib (PTK787 / ZK222584, Novartis / Schering AG); MAPK extracellular regulated kinase I inhibitor CI-1040 (Pharmacia); quinazolines, e.g., PD 153035, 4-(3-chloroanilino)quinazoline; pyridopyrimidines; pyrimidopyrimidines; pyrrolopyrimidines, e.g., CGP 59326, CGP 60261 and CGP 62706; pyrazolopyrimidines, 4-(phenylamino)-7H-pyrrolo[2,3-d]pyrimidine; curcumin (diferuloylmethane, 4,5-bis(4-fluoroanilino)phthalimide); tyrphostins containing a nitrothiophene moiety; PD-0183805 (Warner-Lambert); antisense molecules (e.g., those that bind to HER-encoding nucleic acids); quinoxalines (U.S. Patent No. 5,804,396); triciribine (U.S. Patent No. 5,804,396); ZD6474 (Astra Zeneca); PTK-787 (Novartis / Schering AG); pan-HER inhibitors, e.g., CI-1033 (Pfizer); Affinitac (ISIS 3521; Isis / Lilly); PKI 166 (Novartis);GW2016 (Glaxo SmithKline); CI-1033 (Pfizer); EKB-569 (Wyeth); Semaxinib (Pfizer); ZD6474 (AstraZeneca); PTK-787 (Novartis / Schering AG); INC-1C11 (Imclone); and Rapamycin (Sirolimus, RAPAMUNE (registered trademark)); Proteasome inhibitors such as Bortezomib (VELCADE (registered trademark), Millennium Pharm.); Disulfiram; Epigallocatechin gallate; Salinosporamide A; Carfilzomib; 17-AAG (Geldanamycin); Radicicol; Lactate dehydrogenase A (LDH-A); Fulvestrant (FASLODEX (registered trademark), AstraZeneca); Letrozole (FEMARA (registered trademark), Novartis), Finasteride (VATALANIB (registered trademark), Novartis); Oxaliplatin (ELOXATIN (registered trademark), Sanofi); 5-FU (5-Fluorouracil); Leucovorin; Lonafarnib (SCH 66336); Sorafenib (NEXAVAR (registered trademark), Bayer Labs); AG1478, Alkylating agents such as Thiotepa and CYTOXAN (registered trademark), Cyclophosphamide; Alkyl sulfonates such as Busulfan, Inprosulfan, Piposulfan; Aziridine compounds such as Benzodopa, Carbocone, Metdopa, Uredopa; Ethylenimines and methylamines such as Altretamine, Triethylenemelamine, Triethylenephosphoramide, Triethylenethiophosphoramide, Trimethylmelamine; Acetogenins (especially, Bullatacin and Bullatacinone); Camptothecin (including Topotecan and Irinotecan); Bryostatin; Calistatin; CC-1065 (including its adozelesin, carzelesin and bizelesin synthetic analogs); Cryptophycins (especially Cryptophycin 1 and Cryptophycin 8); Corticosteroids (such as Prednisone and Prednisolone); Cyproterone acetate; 5α-Reductase including Finasteride, Dutasteride; Vorinostat, Romidepsin, Panobinostat, Valproic acid, Mocetinostat, Drastatins;Aldesleukin, talidomide (including synthetic analogs, KW-2189, CB1-TM1); eleutherobin; pancratistatin; sarcodictyin; spongistatin; nitrogen mustards such as chlorambucil, chromafazine, chlorophosphamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, nobenbiptin, phenesterone, prednimustine, trophosphamide, uracil mustard; nitrosoureas such as carmustine, chloroozotocin, fotemustine, lomustine, nimustine, ranimustine; antibiotics such as enediyne antibiotics (e.g., calicheamicin, especially calicheamicin γ1, calicheamicin ω1); dynemicin including dynemicin A; bisphosphonates such as clodronate; esperamicin; and neocarzinostatin chromophore and related chromoprotein enediyne antibiotic chromophores), aclacinomycin, actinomycin, authramycin, azaserine, cactinomycin, carabicin, caminomycin, cardinophilin, chromomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycin C and other mitomycins, mycophenolic acid, nogalamycin, olivomycin, peplomycin, porfiromycin, promycin, keramycin, rhodomycin, streptozocin, streptozocin, tubercidin, ubenimex, dinostatin, zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folic acid analogs such as denopterin, methotrexate, pteropterin, trimethoprim; purine analogs such as fludarabine, 6-mercaptopurine, thiampurine, thioguanine; pyrimidine analogs such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, didoxyridine, doxifluridine, enocitabine, floxuridine;Androgens such as calusterone, drostanolone propionate, epithiostanol, mepitiostane, and testolactone; adrenocortical suppressants such as aminoglutethimide, mitotane, and trilostane; folic acid supplements such as folic acid; aceglutamide; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabucil; bisantrene; edatraxate; defofamine; demeclocycline; diaziquone; elfomithine; elliptinium acetate; epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidamine; maytansinoids such as maytansine and ansamitocin; mitoguazone; mitoxantrone; mopidanol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; podophyllinic acid; 2-ethylhydrazide; procarbazine; PSK (registered trademark) polysaccharide complex (JHS Natural Products); razoxane; lysoxine; sizofiran; spirogermanium; tenuazonic acid; triaziquone; 2,2’,2”-trichloroethylamine; trichothecenes (especially T-2 toxin, verrucarin A, roridin A, and anguidine); urethane; vindesine; dacarbazine; mannomustine; mitobronitol; mitolactol; pipobroman; gacytosine; arabinoside (“Ara-C”); thiotepa; chlorambucil; GEMZAR (registered trademark) (gemcitabine); 6-thioguanine; mercaptopurine; methotrexate; etoposide (VP-16); ifosfamide; mitoxantrone; novantrone; teniposide; edatraxate; daunomycin; aminopterin; capecitabine (XELODA (registered trademark)); ibandronate; CPT-11; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids such as retinoic acid; and pharmaceutically acceptable salts, acids, prodrugs, and derivatives of any of the foregoing.;

[0103] Chemotherapeutic agents also include: (i) antihormonal agents that act to regulate or inhibit the hormonal action on tumors, such as antiestrogens and selective estrogen receptor modulators (SERMs) (including tamoxifen (Nolvadex (registered trademark); including tamoxifen citrate), raloxifene, droloxifene, iodoxyfene, 4-hydroxytamoxifen, trioxifene, keoxifene, LY117018, onapristone, and Fareston (registered trademark) (toremifene citrate)); (ii) aromatase inhibitors that inhibit the enzyme aromatase that regulates estrogen production in the adrenal glands, such as 4(5)-imidazole, aminoglutethimide, Megace (registered trademark) (megestrol acetate), Arimidex (registered trademark) (anastrozole; AstraZeneca), Aromasin (registered trademark) (exemestane; Pfizer), formestane, fadrozole, Rivisor (registered trademark) (vorozole), Femara (registered trademark) (letrozole; Novartis), and Arimidex (registered trademark) (anastrozole; AstraZeneca); (iii) antiandrogens such as flutamide, nilutamide, bicalutamide, leuprorelin, and goserelin; buserelin, tripterelin, medroxyprogesterone acetate, diethylstilbestrol, Premarin, fluoxymesterone, all-trans retinoic acid, fenretinide, and troxacitabine (1,3-dioxolane nucleoside cytosine analog); (iv) protein kinase inhibitors; (v) lipid kinase inhibitors; (vi) antisense oligonucleotides, particularly those that inhibit the expression of genes in signal transduction pathways involved in abnormal cell proliferation, such as PKC-alpha, Ralf, and H-Ras; (vii) ribozymes such as VEGF expression inhibitors (e.g., Angizyme (registered trademark)) and HER2 expression inhibitors; (viii) gene therapy vaccines, such as vaccines like ALLOVECTIN (registered trademark), Leuvectin (registered trademark), and Vaxid (registered trademark).(ix) Growth inhibitors including vinca (e.g., vincristine and vinblastine), Navelbine® (vinorelbine), taxanes (e.g., paclitaxel, nab-paclitaxel, and docetaxel), topoisomerase II inhibitors (e.g., doxorubicin, epirubicin, daunorubicin, etoposide, and bleomycin), and DNA alkylating agents (e.g., tamoxifen, dacarbazine, mechlorethamine, cisplatin, methotrexate, 5-fluorouracil, and ara-C); and (x) pharmaceutically acceptable salts, acids, prodrugs, and derivatives of any of the above are included.;

[0104] As used herein, the term "cytotoxic agent" refers to any agent that is harmful to cells (e.g., causes cell death, inhibits proliferation, or otherwise interferes with cell function). Cytotoxic agents include radioisotopes (e.g., 211 At, 131 I, 125 I, 90 Y, 186 Re, 188 Re, 153 Sm, 212 Bi, 32 P, 212Radioisotopes of Pb and Lu); chemotherapeutic agents; enzymes such as nucleolytic enzymes and fragments thereof; and toxins, such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant or animal origin (including fragments and / or variants thereof), but are not limited thereto. Exemplary cytotoxic agents can be selected from antimicrotubule agents, platinum coordination complexes, alkylating agents, antibiotic agents, topoisomerase II inhibitors, antimetabolites, topoisomerase I inhibitors, hormones and hormone analogs, signal transduction pathway inhibitors, non-receptor tyrosine kinase angiogenesis inhibitors, immunotherapeutic agents, apoptosis promoters, inhibitors of LDH-A, inhibitors of fatty acid biosynthesis, cell cycle signal transduction inhibitors, HDAC inhibitors, proteasome inhibitors, and inhibitors of cancer metabolism. In one case, the cytotoxic agent is a platinum-based chemotherapeutic agent (e.g., carboplatin or cisplatin). In one case, the cytotoxic agent is an antagonist of EGFR, such as N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine (e.g., erlotinib). In one case, the cytotoxic agent is a RAF inhibitor, such as a BRAF and / or CRAF inhibitor. In one case, the RAF inhibitor is vemurafenib. In one case, the cytotoxic agent is a PI3K inhibitor.

[0105] The term "package insert" is used to refer to the instructions normally included in the commercial package of a therapeutic product and contains information regarding indications, uses, dosages, administrations, combination therapies, contraindications and / or warnings for such therapeutic products.

[0106] III. Treatment methods A method of treating a subject or population of subjects having relapsed and / or refractory (R / R) non-Hodgkin lymphoma (NHL) (e.g., R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL)) by intravenous administration of mosunetuzumab (e.g., by intravenous infusion) is provided herein. In some embodiments, a method of treating a subject or population of subjects having indolent NHL (e.g., grade 1, 2, or 3a but not 3b FL) or aggressive NHL (e.g., DLBCL, trFL, or grade 3b FL) is provided herein. In some cases, the subject or population of subjects is relapsed and / or refractory (R / R) to two or more prior treatment lines while maintaining an acceptable safety profile (e.g., with respect to the frequency and severity of adverse events such as cytokine release syndrome (CRS)). In some cases, the two or more prior treatment lines include an anti-CD20 monoclonal antibody and / or an alkylating agent. In some cases, the subject may be ineligible for autologous stem cell transplantation (ASCT).

[0107] A. Treatment methods for administration of mosunetuzumab In one aspect, the present invention provides a method of treating a subject or population of subjects about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having relapsed or refractory (R / R) non-Hodgkin lymphoma (NHL; e.g., R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL)), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); and (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, or ± 3 mg; e.g., 30 mg).In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and C3D1 is 30 ± 6 mg.

[0108] In some cases, the first dosing cycle, the second dosing cycle, and the third dosing cycle are each dosing cycles of 21 days (±1 day). In some cases, the method includes administering C1D1, C1D2, and C1D3 on the 1st day, the 8th day (±1 day), and the 15th day (±1 day) of the first dosing cycle, respectively. In some cases, the method includes administering C2D1 on the 1st day of the second dosing cycle. In some cases, the method includes administering C3D1 on the 1st day of the third dosing cycle.

[0109] In some cases, the dosing regimen further includes one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more) additional dosing cycles. In some cases, the dosing regimen includes 5 to 14 (5, 6, 7, 8, 9, 10, 11, 12, 13, or 14) additional dosing cycles. In certain cases, the dosing regimen includes 5 additional dosing cycles. In another specific case, the dosing regimen includes 14 additional dosing cycles. In some cases, one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more) additional dosing cycles are each dosing cycles of 21 days (±1 day).

[0110] In some cases, each of one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more) additional dosing cycles includes an additional single dose of mosunetuzumab. In some cases, the additional single dose of mosunetuzumab is administered to the subject on day 1 of each additional dosing cycle. In some cases, the additional single dose of mosunetuzumab is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, or ± 3 mg; e.g., 30 mg). In some embodiments, each additional dose of mosunetuzumab is 30 ± 6 mg.

[0111] In one aspect, the present invention provides a method of treating a population of subjects having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL) who are about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older), the method comprising intravenously administering mosunetuzumab to each subject according to a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ±0.2 mg, C1D2 is 2 ±0.4 mg, C1D3 is 60 ±12 mg, C2D1 is 60 ±12 mg, and C3D1 is 30 ±6 mg.

[0112] In one aspect, the present invention provides a method for treating a population of subjects about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C8D1 is 30 ± 6 mg.

[0113] In one aspect, the present invention provides a method of treating a population of subjects about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 17 dosing cycles of 21 days (±1 day), wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C17D1 is 30 ± 6 mg.

[0114] In some cases, the objective response rate in a population of subjects treated with the dosing regimens described herein is 65% or greater (e.g., 70% or greater, 75% or greater, 80% or greater, 85% or greater, 90% or greater, or 95% or greater; e.g., 65 - 100%, 70 - 100%, 75 - 100%, 80 - 100%, 85 - 100%, 90 - 100%, 95 - 100%, 65 - 90%, 65 - 80%, 65 - 70%, 75 - 90%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%). In some cases, the objective response rate in a population of subjects is 75% or greater. In some cases, the objective response rate in a population of subjects is 85% or greater. In some cases, the objective response rate in a population of subjects is 85% or greater.

[0115] In some cases, the complete response rate in a population of subjects treated with the dosing regimens described herein is 50% or greater (e.g., 55% or greater, 60% or greater, 65% or greater, 70% or greater, 75% or greater, 80% or greater, 85% or greater, 90% or greater, or 95% or greater; e.g., 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 50 - 90%, 50 - 80%, 50 - 70%, 50 - 60%, 50% - 75%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%). In some cases, the complete response rate in a population of subjects is 60% or greater. In some cases, the complete response rate in a population of subjects is 70% or greater.

[0116] In some cases, more than 40% (e.g., 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more; e.g., 40 - 100%, 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 40 - 90%, 40 - 80%, 40 - 70%, 40 - 60%, 40 - 50%, 50% - 70%, 50 - 60%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%) of the subjects in a population of subjects treated with the dosing regimens described herein having an objective response maintained remission for 18 months. In some cases, more than 50% of the subjects having an objective response maintained remission for 18 months.

[0117] In some cases, more than 50% (e.g., 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more; e.g., 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 50 - 90%, 50 - 80%, 50 - 70%, 50 - 60%, 50% - 75%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%) of the subjects in a population of subjects treated with the dosing regimens described herein having a complete response maintained complete remission for 18 months. In some cases, more than 60% of the subjects having a complete response maintained complete remission for 18 months.

[0118] In some cases, the median duration of response of subjects in a population of subjects treated with the dosing regimen is 9 months or more (e.g., 9, 10, 11, 12, 13, 14, 15, 18, 21, 24, 27, 30, 33, 36 months or more; e.g., 9 - 12 months, 9 - 15 months, 9 - 18 months, 9 - 24 months, 12 - 18 months, 12 - 24 months, 12 - 36 months, 18 - 36 months, 24 - 36 months or more; e.g., 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months or more). In some cases, the median duration of response in the population of subjects is 15 months or more. In some cases, the median duration of response in the population of subjects is 18 months or more.

[0119] In some cases, the median duration of complete response of subjects in a population of subjects treated with the dosing regimen described herein is 12 months or more (e.g., 9, 10, 11, 12, 13, 14, 15, 18, 21, 24, 27, 30, 33, 36 months or more; e.g., 12 - 15 months, 12 - 18 months, 12 - 21 months, 12 - 24 months, 12 - 30 months, 12 - 36 months, 15 - 18 months, 15 - 24 months, 18 - 24 months, 24 - 36 months, 18 - 36 months or more; e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months or more). In some cases, the median duration of complete response in the population of subjects is 16 months or more. In some cases, the median duration of complete response in the population of subjects is 18 months or more.

[0120] In some cases, more than 35% of the subjects (e.g., 40% or more, 45% or more, 50% or more, 55% or more, 60% or more, 65% or more, 70% or more, 75% or more, 80% or more, 85% or more, 90% or more, or 95% or more; e.g., 35 - 100%, 40 - 100%, 50 - 100%, 60 - 100%, 70 - 100%, 80 - 100%, 90 - 100%, 95 - 100%, 35 - 90%, 35 - 80%, 35 - 70%, 35 - 60%, 35 - 50%, 35 - 45%, 40 - 80%, 40 - 60%, 50% - 70%, 50 - 60%, 75 - 90%, 60 - 80%, 75 - 85%, 70 - 90%, or 80 - 90%; e.g., about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%) of the population of subjects treated with the dosing regimen described herein have progression-free survival of 18 months. In some cases, more than 45% of the subjects have progression-free survival of 18 months.

[0121] In some cases, the median progression-free survival in the population of subjects is 12 months or more (e.g., 9, 10, 11, 12, 13, 14, 15, 18, 21, 24, 27, 30, 33, 36 months or more, or more than that; e.g., 12 - 15 months, 12 - 18 months, 12 - 21 months, 12 - 24 months, 12 - 30 months, 12 - 36 months, 15 - 18 months, 15 - 24 months, 18 - 24 months, 24 - 36 months, 18 - 36 months, or more than that; e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months, or more than that). In some cases, the median progression-free survival in the population of subjects is 17 months or more.

[0122] In one aspect, the present invention provides a method of achieving objective response, complete response or progression-free survival in subjects about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ±0.2 mg, C1D2 is 2 ±0.4 mg, C1D3 is 60 ±12 mg, C2D1 is 60 ±12 mg, and C3D1 is 30 ±6 mg.

[0123] In one aspect, the present invention provides a method for achieving objective response, complete response or progression-free survival in a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C8D1 is 30 ± 6 mg.

[0124] In one aspect, the present invention provides a method of achieving objective response, complete response or progression-free survival in a subject of about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 17 cycles of 21-day (±1-day) dosing cycles, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg). In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C17D1 is 30 ± 6 mg.

[0125] In some cases, the subject achieves an objective response. In some cases, the subject achieves a complete response. In some cases, progression-free survival is maintained for 12 months or more (e.g., 12 - 15 months, 12 - 18 months, 12 - 21 months, 12 - 24 months, 12 - 30 months, 12 - 36 months, 15 - 18 months, 15 - 24 months, 18 - 24 months, 24 - 36 months, or 18 - 36 months; e.g., 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 24, 27, 30, 33, 36 months, or more). In some cases, progression-free survival is maintained for 18 months or more.

[0126] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ±0.2 mg, C1D2 is 2 ±0.4 mg, C1D3 is 60 ±12 mg, C2D1 is 60 ±12 mg, and C3D1 is 30 ±6 mg.

[0127] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C8D1 is 30 ± 6 mg.

[0128] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 cycles of 21-day (±1 day) dosing cycles, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1-C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1-C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C17D1 is 30 ± 6 mg.

[0129] In one aspect, the present invention provides a method of treating a subject having R / R FL who is about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein: (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and C3D1 is 30 ± 6 mg.

[0130] In one aspect, the present invention provides a method of treating a subject 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R FL, the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C8D1 is 30 ± 6 mg.

[0131] In one aspect, the present invention provides a method for treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R FL, the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 dosing cycles of 21 days (±1 day), wherein: (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C17D1 is 30 ± 6 mg.

[0132] In some cases, each subject in a population of subjects treated with the dosing regimens described herein and / or subjects treated with the dosing regimens described herein has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some cases, the two or more prior treatment lines include an anti - CD20 monoclonal antibody (e.g., rituximab), an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa), or both an anti - CD20 monoclonal antibody and an alkylating agent.

[0133] In some cases, the R / R NHL described herein is R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B - cell lymphoma (DLBCL). In certain cases, the R / R NHL is R / R FL. In certain cases, the FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375 - 90), but not 3b.

[0134] In certain cases, mosunetuzumab is administered by intravenous infusion to a subject treated with the dosing regimens described herein and / or to each subject in a population of subjects treated with the dosing regimens described herein.

[0135] In some cases, the subject(s) described herein is / are human subject(s).

[0136] In some cases, the median progression-free survival period of a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is higher than the reference median progression-free survival period of a reference population of subjects treated with the same dosing regimen (e.g., about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% higher or higher than that).

[0137] In some cases, the complete response rate in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is higher than the reference complete response rate of a reference population of subjects treated with the same dosing regimen (e.g., about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% higher or higher than that).

[0138] In some cases, the objective response rate in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is higher than the reference objective response rate of a reference population of subjects treated with the same dosing regimen (e.g., about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50% higher or higher than that).

[0139] In some cases, the reference population of interest does not include elderly subjects. In certain cases, each subject in the reference population of interest is about 18 to 64 years old. In some cases, the reference population of interest has relapsed / refractory NHL (e.g., relapsed / refractory FL, relapsed / refractory trFL, or relapsed / refractory DLBCL). In certain cases, the relapsed / refractory NHL is relapsed / refractory FL. In certain cases, FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization classification of lymphoid neoplasms (referenced in Swerdlow SH, et al. Blood 2016;127:2375-90), but not 3b. In some cases, each subject in the reference population of interest has relapsed or is refractory after two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines. In some cases, the two or more prior treatment lines include an anti-CD20 monoclonal antibody (e.g., rituximab), an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa), or both an anti-CD20 monoclonal antibody and an alkylating agent.

[0140] B. Administration Strategies to Reduce Adverse Events The present invention relates to a method of treating a subject or population of subjects who are about 65 years of age or older and have R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL) by intravenous administration of mosunetuzumab while maintaining an acceptable safety profile (e.g., with respect to the frequency and severity of adverse events (AE), such as cytokine release syndrome (CRS), including severe adverse events (SAE)). In some cases, the subject or population of subjects is refractory and / or relapsed (R / R) to two or more prior treatment lines while maintaining an acceptable safety profile (e.g., with respect to the frequency and severity of adverse events such as cytokine release syndrome (CRS)). In some cases, the two or more prior treatment lines include an anti-CD20 monoclonal antibody and / or an alkylating agent. In some cases, the subject may be ineligible for autologous stem cell transplantation (ASCT).

[0141] 1. Symptoms and Grading of CRS Any of the methods described herein may involve monitoring the subject for cytokine release syndrome (CRS) (e.g., CRS events after initiation of any of the above methods). Current clinical management focuses on treating individual signs and symptoms, providing supportive therapy, and attempting to attenuate the inflammatory response using high-dose corticosteroids. However, this approach does not always succeed, especially in the case of late intervention. The CRS grading criteria used by the methods described herein define mild, moderate, severe, or life-threatening CRS and are published by the American Society for Transplantation and Cellular Therapy (ASTCT) (Lee et al. Biol Blood Marrow Transplantation. 25(4):625-638, 2019) to harmonize reporting across clinical trials and enable rapid recognition and treatment of CRS. The ASTCT criteria are objective, easy to apply, and intended to more accurately classify the severity of CRS. This CRS grading system is shown in Table 1 below.

Table 1

[0142] Fever is defined as a body temperature of 38°C or higher not attributable to other causes. Subsequently, in subjects with CRS, once they receive antipyretics or anti-cytokine therapies such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity. In this case, CRS grading is determined by hypotension and / or hypoxia.

[0143] CRS grade is determined by more severe events not attributable to other causes, hypotension, or hypoxia. For example, a subject with a temperature of 39.5°C, hypotension requiring one pressor agent, and hypoxia requiring a low-flow nasal cannula is classified as grade 3 CRS.

[0144] A low-flow nasal cannula is defined as oxygen delivered at 6 L / min or less. Low flow also includes blow-by oxygen delivery sometimes used in pediatrics. A high-flow nasal cannula is defined as oxygen delivered at more than 6 L / min.

[0145] CRS is associated with an increase in various cytokines, with marked increases in IFNγ, IL-6, and TNF-α levels. The evidence that has emerged particularly associates CRS and IL-6 as central mediators. IL-6 is a pro-inflammatory multifunctional cytokine produced by various cell types, and this cytokine has been shown to be involved in a wide variety of physiological processes with T cell activation. Regardless of the inducer, CRS is associated with high IL-6 levels (Nagorsen et al. Cytokine. 25(1):31-5, 2004; Lee et al. Blood. 124(2):188-95, 2014; Doesegger et al. Clin. Transl. Immunol. 4(7):e39, 2015), and IL-6 correlates with the severity of CRS. Subjects experiencing grade 4 or 5 CRS events have much higher IL-6 levels compared to subjects who do not experience CRS or who experience milder CRS (grades 0-3) (Chen et al., J. Immunol. Methods. 434:1-8, 2016).

[0146] Therefore, blocking the inflammatory action of IL-6 using an agent that inhibits IL-6-mediated signaling to manage CRS observed in subjects during a two-step fractionated dose escalation regimen is considered an alternative to steroid treatment that is not expected to adversely affect T cell function in the treatment of CD20-positive cell proliferative disorders (e.g., B cell proliferative disorders), or to reduce the efficacy or clinical benefit of mosunetuzumab therapy.

[0147] If a subject has a CRS event that does not recover or worsen within 24 hours after administration of an IL-6R antagonist to treat the symptoms of the CRS event, this method can further comprise administering one or more additional doses of the IL-6R antagonist to the subject to manage the CRS event. If the CRS event is not managed through administration of the IL-6R antagonist, the subject can be administered a corticosteroid such as methylprednisolone or dexamethasone.

[0148] 2. Other Adverse Events and Grading Any of the methods described herein may include monitoring the subject for additional non-CRS adverse events. Physical findings and the incidence, nature, and severity of adverse events having a severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0; cancer.gov).

[0149] 3. Dosage Regimens with an Acceptable Safety Profile The present invention relates to a method of treating a subject or population of subjects who are about 65 years of age or older and have R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL) by intravenous administration of mosunetuzumab while maintaining an acceptable safety profile. In particular, the present invention features dosage regimens comprising mosunetuzumab and one or more additional therapeutic agents useful for maintaining an acceptable safety profile and / or reducing the risk of adverse events (e.g., cytokine release syndrome (CRS) events). In some cases, the dosage regimen includes a pre-dose treatment of administering one or more additional therapeutic agents prior to administering any dose of mosunetuzumab (e.g., prior to administering C1D1, C1D2, C1D3, or any C2D1-C17D1 dose of mosunetuzumab). In some cases, the dosage regimens described herein include pre-dose treatment with corticosteroids, antihistamines, and / or antipyretics. In certain cases, the dosage regimens described herein include pre-dose treatment with corticosteroids, antihistamines, and antipyretics. In another specific case, the dosage regimens described herein include pre-dose treatment with corticosteroids. In other cases, the subject is administered one or more additional therapeutic agents after experiencing an adverse event (e.g., a CRS event). In some cases, the subject is administered a corticosteroid or an IL-6R antagonist (e.g., tocilizumab) after experiencing an adverse event (e.g., a CRS event). In a specific case, the subject is administered tocilizumab after experiencing a CRS event.

[0150] In some cases, the method further comprises administering to the subject or each subject in the population of subjects one or more (e.g., 1, 2, 3, 4, 5, 6, or more) additional therapeutic agents.

[0151] In some cases, the one or more (e.g., 1, 2, 3, 4, 5, 6, or more) additional therapeutic agents include tocilizumab.

[0152] In some cases, one or more additional therapeutic agents (e.g., 1, 2, 3, 4, 5, 6, or more) include corticosteroids. In some cases, corticosteroids include dexamethasone or methylprednisolone. In some cases, corticosteroids are administered to the subject or each subject in the population of subjects at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) prior to the administration of any dose of mosunetuzumab. In some cases, corticosteroids are administered only during administration cycle 1 or administration cycle 2. In some cases, corticosteroids are additionally administered during one or more administration cycles after administration cycle 2 (e.g., in administration cycles 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and / or 17). In some cases, corticosteroids are administered intravenously. In some cases, corticosteroids include dexamethasone and are administered at a dose of about 20 mg (e.g., 20 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg or ± 2 mg; e.g., 20 mg). In some cases, corticosteroids include methylprednisolone and are administered at a dose of about 80 mg (e.g., 80 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 8 mg, ± 7 mg, or ± 8 mg; e.g., 80 mg).

[0153] In some cases, one or more additional therapeutic agents (e.g., 1, 2, 3, 4, 5, 6, or more) include antihistamines. In some cases, the antihistamine is administered to the subject or each subject in the population of subjects at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) prior to the administration of any dose of mosunetuzumab. In some cases, the antihistamine is administered only during administration cycle 1 or administration cycle 2. In some cases, the antihistamine is additionally administered during the period of one or more administration cycles after administration cycle 2 (e.g., in administration cycles 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and / or 17). In some cases, the antihistamine is administered orally or intravenously. In some cases, the antihistamine includes diphenhydramine hydrochloride and is administered at a dose of about 50-100 mg (e.g., 50-90 mg, 50-80 mg, 50-70 mg, 50-60 mg, 60-100 mg, 70-100 mg, 80-100 mg, 90-100 mg, 70-80 mg, 60-90 mg, 60-80 mg, 70-90 mg, or 65-85 mg; e.g., about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, or about 100 mg).

[0154] In some cases, one or more additional therapeutic agents (e.g., 1, 2, 3, 4, 5, 6, or more) include an antipyretic. In some cases, the antipyretic is administered to the subject or each subject in the population of subjects at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) prior to the administration of any dose of mosunetuzumab. In some cases, the antipyretic is administered only during administration cycle 1 or administration cycle 2. In some cases, the antipyretic is additionally administered during the period of one or more administration cycles after administration cycle 2 (e.g., in administration cycles 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 and / or 17). In some cases, the antipyretic is administered orally. In some cases, the antipyretic contains acetaminophen and is administered at a dose of about 500 - 1000 mg (e.g., 500 - 900 mg, 500 - 800 mg, 500 - 700 mg, 500 - 600 mg, 600 - 1000 mg, 700 - 1000 mg, 800 - 1000 mg, 900 - 1000 mg, 700 - 800 mg, 600 - 900 mg, 600 - 800 mg, 700 - 900 mg, or 650 - 850 mg; e.g., about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg).

[0155] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and C3D1 is 30 ± 6 mg.

[0156] In one aspect, the present invention provides a method of treating a subject of about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after two or more prior (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) treatment lines or is refractory thereto, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C8D1 is 30 ± 6 mg.

[0157] In one aspect, the present invention provides a method of treating a subject about 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R NHL (e.g., R / R FL, R / R DLBCL, or R / R trFL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty-one day (±1 day) dosing cycles, wherein: (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, wherein C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, or ±0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, or ±0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, ±3 mg, ±4 mg, ±5 mg, ±6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1-C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, wherein each of C3D1-C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ±0.025 mg, ±0.05 mg, ±0.075 mg, ±0.1 mg, ±0.2 mg, ±0.3 mg, ±0.4 mg, ±0.5 mg, ±0.75 mg, ±1 mg, ±1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after or is refractory to two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 to C17D1 is 30 ± 6 mg.

[0158] In one aspect, the present invention provides a method of treating a subject 65 years of age or older (e.g., 65 years of age or older, 70 years of age or older, 75 years of age or older, 80 years of age or older, 85 years of age or older, 90 years of age or older, 95 years of age or older, or 100 years of age or older) having R / R FL, the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day (±1 day) dosing cycle, a second 21-day (±1 day) dosing cycle, and a third 21-day (±1 day) dosing cycle, wherein (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, C3D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and C3D1 is 30 ± 6 mg.

[0159] In one aspect, the present invention provides a method of treating a subject aged about 65 years or older (e.g., 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, 95 years or older, or 100 years or older) with relapsed / refractory follicular lymphoma (R / R FL), the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days (±1 day), wherein: (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on day 1, day 8 (±1 day), and day 15 (±1 day) of the first dosing cycle, respectively, C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after two or more prior (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) treatment lines or is refractory thereto, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C8D1 is 30 ± 6 mg.

[0160] In one aspect, the present invention provides a method for treating a subject aged about 65 years or older (e.g., 65 years or older, 70 years or older, 75 years or older, 80 years or older, 85 years or older, 90 years or older, 95 years or older, or 100 years or older) with R / R FL, the method comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty-one day (±1 day) dosing cycles, wherein: (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8 (±1 day), and 15 (±1 day) of the first dosing cycle, respectively, where C1D1 is about 1 mg (e.g., 1 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, or ± 0.1 mg; e.g., 1 mg), C1D2 is about 2 mg (e.g., 2 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, or ± 0.2 mg; e.g., 2 mg), and C1D3 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg (e.g., 60 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 6 mg; e.g., 60 mg); (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, where each of C3D1 - C17D1 is about 30 mg (e.g., 30 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ±2 mg, or ±3 mg; for example, 30 mg), and the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior treatment lines, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of corticosteroid is administered to the subject at least 1 hour (e.g., 60, 70, 80, 90, 120, 150, 180, 210, 240, 300 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of antihistamine is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of antipyretic is administered to the subject at least 30 minutes (e.g., 30, 35, 40, 45, 50, 60, 70, 80, 90, 120, 150, 180 minutes, or more) before each administration of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab. In some embodiments, C1D1 is 1 ± 0.2 mg, C1D2 is 2 ± 0.4 mg, C1D3 is 60 ± 12 mg, C2D1 is 60 ± 12 mg, and each of C3D1 - C17D1 is 30 ± 6 mg.

[0161] In some cases, the subject has relapsed after, or is refractory to, two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior lines of therapy. In some cases, the two or more prior lines of therapy include an anti-CD20 monoclonal antibody (e.g., rituximab), an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa), or both an anti-CD20 monoclonal antibody and an alkylating agent.

[0162] In some cases, R / R NHL is R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL). In certain cases, R / R NHL is R / R FL. In certain cases, FL is histologically proven to be grade 1, 2, or 3a, but not 3b, according to the World Health Organization classification of lymphoid neoplasms (see Swerdlow SH, et al. Blood 2016;127:2375-90).

[0163] In certain cases, mosunetuzumab is administered by intravenous infusion.

[0164] In some cases, (i) a single dose of corticosteroid is administered prior to the administration of any dose of mosunetuzumab in any one or more of the dosing cycles after the second dosing cycle (e.g., prior to the administration of C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1 and / or C14D1 of mosunetuzumab); (ii) a single dose of antihistamine is administered prior to the administration of any dose of mosunetuzumab in any one or more of the dosing cycles after the second dosing cycle (e.g., prior to the administration of C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1 and / or C14D1 of mosunetuzumab); and / or (iii) a single dose of antipyretic is administered prior to the administration of any dose of mosunetuzumab in any one or more of the dosing cycles after the second dosing cycle (e.g., prior to the administration of C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1 and / or C14D1 of mosunetuzumab).

[0165] In some cases, (i) the corticosteroid is administered intravenously; (ii) the antihistamine is administered orally or intravenously; and / or (iii) the antipyretic is administered orally.

[0166] In some cases, (i) the corticosteroid includes dexamethasone and is administered at a dose of about 20 mg (e.g., 20 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, or ± 2 mg; e.g., 20 mg), or the corticosteroid includes methylprednisolone and is administered at a dose of about 80 mg (e.g., 80 mg ± 0.01 mg, ± 0.025 mg, ± 0.05 mg, ± 0.075 mg, ± 0.1 mg, ± 0.2 mg, ± 0.3 mg, ± 0.4 mg, ± 0.5 mg, ± 0.75 mg, ± 1 mg, ± 1.5 mg, ± 2 mg, ± 3 mg, ± 4 mg, ± 5 mg, ± 8 mg, ± 7 mg, or ± 8 mg; e.g., 80 mg); (ii) the antihistamine includes diphenhydramine hydrochloride and is administered at a dose of about 50 - 100 mg (e.g., 50 - 90 mg, 50 - 80 mg, 50 - 70 mg, 50 - 60 mg, 60 - 100 mg, 70 - 100 mg, 80 - 100 mg, 90 - 100 mg, 70 - 80 mg, 60 - 90 mg, 60 - 80 mg, 70 - 90 mg, or 65 - 85 mg; e.g., about 50 mg, about 55 mg, about 60 mg, about 65 mg, about 70 mg, about 75 mg, about 80 mg, about 85 mg, about 90 mg, about 95 mg, or about 100 mg); and / or (iii) the antipyretic is acetaminophen and is administered at a dose of about 500 - 1000 mg (e.g., 500 - 900 mg, 500 - 800 mg, 500 - 700 mg, 500 - 600 mg, 600 - 1000 mg, 700 - 1000 mg, 800 - 1000 mg, 900 - 1000 mg, 700 - 800 mg, 600 - 900 mg, 600 - 800 mg, 700 - 900 mg, or 650 - 850 mg; e.g., about 500 mg, about 550 mg, about 600 mg, about 650 mg, about 700 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, or about 1000 mg).

[0167] In some cases, the percentage of serious adverse events excluding grade 5 malignant neoplasm progression in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is 45% or less (e.g., 40%, 35%, 30%, 25%, 20%, 15%, 10%, or 5% or less; e.g., 0 - 45%, 0 - 35%, 0 - 25%, 0 - 15%, 0 - 10%, 0 - 5%, 5 - 15%, 15 - 30%, 30 - 45%, 10 - 30%, 20 - 40%, 35 - 45%, 30 - 40%, 20 - 30%, or 10 - 20%; e.g., about 0%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40% or about 45%). In some cases, the percentage of serious adverse events excluding grade 5 malignant neoplasm progression in a population of subjects is 40% or less. In some cases, the percentage of serious adverse events excluding grade 5 malignant neoplasm progression in a population of subjects is 50% or less (e.g., about 50%, about 49%, about 48%, about 47%, or about 46%).

[0168] In some embodiments, the percentage of serious adverse events related to mosunetuzumab in a population of subjects is 40% or less (e.g., 35%, 30%, 25%, 20%, 15%, 10%, or 5% or less; e.g., 0 - 40%, 0 - 35%, 0 - 25%, 0 - 15%, 0 - 10%, 0 - 5%, 5 - 15%, 15 - 30%, 30 - 40%, 10 - 30%, 20 - 40%, 30 - 40%, 20 - 30%, or 10 - 20%; e.g., about 0%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35% or about 40%). In some embodiments, the percentage of serious adverse events related to mosunetuzumab in a population of subjects is 30% or less. In some cases, the percentage of serious adverse events related to mosunetuzumab in a population of subjects is 35% or less.

[0169] In some cases, the percentage of cytokine release syndrome of grade 3 or higher (as defined by the American Society for Transplantation and Cellular Therapy, 2018; ASTCT) in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is 5% or less (e.g., 4%, 3%, 2%, or 1% or less; e.g., 0 - 5%, 1 - 5%, 2 - 5%, 3 - 5%, 4 - 5%, 1 - 3%, 2 - 4%, or 0 - 3%; e.g., about 0%, about 1%, about 2%, about 3%, about 4%, or about 5%). In some cases, the percentage of cytokine release syndrome having a grade of 3 or higher (as defined by ASTCT) in the population of subjects is 3% or less.

[0170] In some cases, the percentage of cytokine release syndrome of any grade (as defined by ASTCT) in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is 40% or less (e.g., 35%, 30%, 25%, 20%, 15%, 10%, or 5% or less; e.g., 0 - 40%, 0 - 35%, 0 - 25%, 0 - 15%, 0 - 10%, 0 - 5%, 5 - 15%, 15 - 30%, 25 - 40%, 10 - 30%, 20 - 40%, 25 - 35%, 35 - 40%, 30 - 40%, 20 - 30%, or 10 - 20%; e.g., about 0%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35% or about 40%). In some cases, the percentage of cytokine release syndrome of any grade (as defined by ASTCT) in the population of subjects is 30% or less. In some embodiments, the percentage of cytokine release syndrome of any grade (as defined by ASTCT) in the population of subjects is 50% or less (e.g., 45% or less; e.g., 40 - 50%, 30 - 50%, 25 - 50%, 20 - 50%, 10 - 50%, 0 - 50%, 40 - 45%, 30 - 35%, 20 - 45%, 10 - 45%, 0 - 45%; e.g., about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50%).

[0171] In some cases, the rate of serious adverse events (SAEs), excluding grade 5 malignant neoplasm progression, in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is lower (e.g., by about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or more) than the reference rate of SAEs, excluding grade 5 malignant neoplasm progression, in a reference population of subjects treated with the same dosing regimens.

[0172] In some cases, the rate of serious adverse events (SAEs) associated with mosunetuzumab in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is lower (e.g., by about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or more) than the reference rate of SAEs associated with mosunetuzumab in a reference population of subjects treated with the same dosing regimens.

[0173] In some cases, the rate of cytokine release syndrome (CRS) events in a population of subjects (i.e., elderly subjects) treated with the dosing regimens described herein is lower (e.g., by about 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, or more) than the reference rate of CRS events in a reference population of subjects treated with the same dosing regimens.

[0174] In some cases, the reference population of interest does not include elderly subjects. In certain cases, each subject in the reference population of interest is about 18 to 64 years old. In some cases, the reference population of interest has relapsed / refractory NHL (e.g., relapsed / refractory FL, relapsed / refractory trFL, or relapsed / refractory DLBCL). In certain cases, the relapsed / refractory NHL is relapsed / refractory FL. In certain cases, the FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90), but not 3b. In some cases, each subject in the reference population of interest has relapsed or is refractory after two or more (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or more) prior lines of therapy. In some cases, the two or more prior lines of therapy include an anti-CD20 monoclonal antibody (e.g., rituximab), an alkylating agent (e.g., bendamustine, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, carmustine, lomustine, streptozocin, busulfan, dacarbazine, temozolomide, altretamine, or thiotepa), or both an anti-CD20 monoclonal antibody and an alkylating agent.

[0175] In some cases, one or more additional therapeutic agents are corticosteroids or IL-6R antagonists and are used to treat subjects experiencing cytokine release syndrome (CRS). In some cases, one or more additional therapeutic agents are IL-6R antagonists. In some cases, the IL-6R antagonist is tocilizumab. In some cases, tocilizumab is administered to a subject as a single dose of about 8 mg / kg (e.g., 8 mg / kg ± 0.01 mg / kg, ± 0.025 mg / kg, ± 0.05 mg / kg, ± 0.075 mg / kg, ± 0.1 mg / kg, ± 0.2 mg / kg, ± 0.3 mg / kg, ± 0.4 mg / kg, ± 0.5 mg / kg, ± 0.75 mg / kg, ± 1 mg / kg, ± 1.5 mg / kg, or ± 2 mg / kg; e.g., 8 mg / kg), and the single dose does not exceed 800 mg. In some cases, tocilizumab is administered to a subject as a single dose of about 12 mg / kg (e.g., 12 mg / kg ± 0.01 mg / kg, ± 0.025 mg / kg, ± 0.05 mg / kg, ± 0.075 mg / kg, ± 0.1 mg / kg, ± 0.2 mg / kg, ± 0.3 mg / kg, ± 0.4 mg / kg, ± 0.5 mg / kg, ± 0.75 mg / kg, ± 1 mg / kg, ± 1.5 mg / kg, or ± 2 mg / kg; e.g., 12 mg / kg), and the single dose does not exceed 800 mg. In some cases, tocilizumab is administered intravenously.

[0176] IV. Therapeutic Agents A. Mosunetuzumab The present invention provides mosunetuzumab, a bispecific antibody that binds to CD20 and CD3, which is useful for the treatment of CD20-positive cell proliferative disorders. In some cases, the CD20-positive cell proliferative disorder is relapsed and / or refractory (R / R) non-Hodgkin lymphoma (NHL) (e.g., R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL)).

[0177] Mosunetuzumab has an anti-CD20 arm having a first binding domain that includes the following six hypervariable regions (HVRs): (a) HVR-H1 comprising the amino acid sequence of GYTFTSYNMH (SEQ ID NO: 1); (b) HVR-H2 comprising the amino acid sequence of AIYPGNGDTSYNQKFKG (SEQ ID NO: 2); (c) HVR-H3 comprising the amino acid sequence of VVYYSNSYWYFDV (SEQ ID NO: 3); (d) HVR-L1 comprising the amino acid sequence of RASSSVSYMH (SEQ ID NO: 4); (e) HVR-L2 comprising the amino acid sequence of APSNLAS (SEQ ID NO: 5); and (f) HVR-L3 comprising the amino acid sequence of QQWSFNPPT (SEQ ID NO: 6). Mosunetuzumab includes an anti-CD20 arm having a first binding domain that includes heavy chain framework regions FR-H1, FR-H2, FR-H3, and FR-H4, each comprising the sequences of SEQ ID NOS: 17-20, respectively, and light chain framework regions FR-L1, FR-L2, FR-L3, and FR-L4, each comprising the sequences of SEQ ID NOS: 21-24, respectively. Mosunetuzumab includes an anti-CD20 arm having a first binding domain that includes (a) a heavy chain variable (VH) domain comprising the amino acid sequence of SEQ ID NO: 7; and (b) a light chain variable (VL) domain comprising the amino acid sequence of SEQ ID NO: 8.

[0178] Mosunetuzumab has an anti-CD3 arm having a second binding domain that includes the following six HVRs: (a) HVR-H1 that includes the amino acid sequence of NYYIH (SEQ ID NO: 9); (b) HVR-H2 that includes the amino acid sequence of WIYPGDGNTKYNEKFKG (SEQ ID NO: 10); (c) HVR-H3 that includes the amino acid sequence of DSYSNYYFDY (SEQ ID NO: 11); (d) HVR-L1 that includes the amino acid sequence of KSSQSLLNSRTRKNYLA (SEQ ID NO: 12); (e) HVR-L2 that includes the amino acid sequence of WASTRES (SEQ ID NO: 13); and (f) HVR-L3 that includes the amino acid sequence of TQSFILRT (SEQ ID NO: 14). Mosunetuzumab includes an anti-CD3 arm that includes a second binding domain that includes heavy chain framework regions FR-H1, FR-H2, FR-H3, and FR-H4, each including the sequence of SEQ ID NOs: 25-28, respectively, and light chain framework regions FR-L1, FR-L2, FR-L3, and FR-L4, each including the sequence of SEQ ID NOs: 29-32, respectively. Mosunetuzumab includes an anti-CD3 arm that includes a second binding domain that includes (a) a VH domain that includes an amino acid sequence having the amino acid sequence of SEQ ID NO: 15; and (b) a VL domain that includes the amino acid sequence of SEQ ID NO: 16.

[0179] Mosunetuzumab has the International Nonproprietary Name (INN) in List 117 (WHO Drug Information, Vol. 31, No. 2, 2017, p. 303), or the CAS Registry Number 1905409-39-3, and has (1) an anti-CD20 arm that includes a heavy chain sequence and a light chain sequence of SEQ ID NOs: 33 and 34, respectively, and (2) an anti-CD3 arm that includes a heavy chain and a light chain sequence of SEQ ID NOs: 35 and 36, respectively. Mosunetuzumab includes (1) an anti-CD20 arm that includes a first binding domain that includes a heavy chain that includes the amino acid sequence of SEQ ID NO: 33 and a light chain that includes the amino acid sequence of SEQ ID NO: 34, and (2) an anti-CD3 arm that includes a second binding domain that includes a heavy chain that includes the amino acid sequence of SEQ ID NO: 35 and a light chain that includes the amino acid sequence of SEQ ID NO: 36.

[0180] The amino acid sequence of mosunetuzumab is summarized in Table 2 below.

Table 2

[0181] Moxetumomab can be produced using recombinant methods and compositions, for example, as described in U.S. Patent No. 4,816,567.

[0182] B. Additional Therapeutic Agents In some cases, the methods described herein include administering moxetumomab in combination with one or more additional therapeutic agents. In some cases, one or more additional therapeutic agents can reduce the rate or severity of cytokine release syndrome (CRS). In some cases, one or more additional therapeutic agents can prevent symptoms associated with CRS.

[0183] In certain cases, additional therapeutic agents used to reduce the rate or severity of CRS or to prevent symptoms associated with CRS are corticosteroids (e.g., dexamethasone (CAS number: 50-02-2), prednisone (CAS number: 53-03-2), prednisolone (CAS number 50-42-8) or methylprednisolone (CAS#: 83-43-2)) or IL-6R antagonists (e.g., tocilizumab (CAS number: 375823-41-9), sarilumab (CAS number: 1189541-98-7), baricitinib (ALX-0061; CAS number: 1628814-88-9), satralizumab (SA-237; CAS number: 1535963-91-7), and variants thereof).

[0184] In some cases, the additional therapeutic agent is tocilizumab. In some cases, the additional therapeutic agent is a corticosteroid. In some cases, the corticosteroid is dexamethasone. In some cases, the corticosteroid is prednisone. In some cases, the corticosteroid is methylprednisolone.

[0185] In some cases, one or more additional therapeutic agents are antipyretics, such as acetaminophen or paracetamol. Acetaminophen or paracetamol has a CAS number: 103-90-2.

[0186] In some cases, one or more additional therapeutic agents are antihistamines, such as diphenhydramine. Diphenhydramine has a CAS number: 58-73-1. In some embodiments, diphenhydramine is diphenhydramine hydrochloride (CAS number: 147-24-0).

[0187] When the methods described herein involve combination therapies, such as the specific combination therapies described above, the combination therapy includes administration of mosunetuzumab with one or more additional therapeutic agents, and such co-administration can be co-administration (two or more therapeutic agents are included in the same formulation, or separate formulations), or separate administrations, and in this case, administration of mosunetuzumab can occur before, simultaneously with, and / or after administration of the additional therapeutic agent(s).

[0188] In some embodiments, one or more additional therapeutic agents administered in combination with mosunetuzumab are corticosteroids, antihistamines and / or antipyretics. In some embodiments, corticosteroids, antihistamines and / or antipyretics are administered to the subject as a pre-medication for mosunetuzumab administration.

[0189] When the methods described herein involve combination therapies, such as the specific combination therapies described above, the combination therapy includes administration of mosunetuzumab with one or more additional therapeutic agents, and such co-administration can be co-administration (two or more therapeutic agents are included in the same formulation, or separate formulations), or separate administrations, and in this case, administration of mosunetuzumab can occur before, simultaneously with, and / or after administration of the additional therapeutic agent(s).

[0190] In some embodiments, the one or more additional therapeutic agents administered in combination with mosunetuzumab are corticosteroids, antihistamines, and / or antipyretics. In some embodiments, the corticosteroids, antihistamines, and / or antipyretics are administered to the subject as a pre-medication for mosunetuzumab administration.

[0191] V. Pharmaceutical Compositions and Formulations The mosunetuzumab described in this specification can be used in pharmaceutical compositions and formulations. The pharmaceutical compositions and formulations of the mosunetuzumab and / or other therapeutic agents (e.g., dexamethasone, methylprednisolone, prednisone, acetaminophen, paracetamol, and diphenhydramine) described in this specification can be in the form of a lyophilized formulation or an aqueous solution, and one, two, or more drugs with the desired purity can be mixed with one or more optional pharmaceutically acceptable carriers (Remington’s Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)). Pharmaceutically acceptable carriers are generally non-toxic to the recipient at the dosages and concentrations used, and include buffers such as phosphates, citrates, and other organic acids, antioxidants including ascorbic acid and methionine, preservatives (octadecyldimethylbenzylammonium chloride, hexamethonium chloride, benzalkonium chloride, benzethonium chloride, phenol, butyl, or benzyl alcohol, alkyl parabens such as methyl or propyl paraben, catechol, resorcinol, cyclohexanol, 3-pentanol, and m-cresol, etc.), low molecular weight (less than about 10 residues) polypeptides, proteins such as serum albumin, gelatin, or immunoglobulins, hydrophilic polymers such as polyvinylpyrrolidone, amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine, monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrin, chelating agents such as EDTA, sugars such as sucrose, mannitol, trehalose, or sorbitol, salt-forming counterions such as sodium, metal complexes (e.g., Zn-protein complexes), and / or nonionic surfactants such as polyethylene glycol (PEG), but are not limited thereto. Exemplary pharmaceutically acceptable carriers herein further include intervening drug dispersants such as soluble neutral active hyaluronidase glycoprotein (sHASEGP), such as human soluble PH-20 hyaluronidase glycoprotein such as rHuPH20 (HYLENEX®, Baxter International, Inc.).Certain exemplary sHASEGPs and methods of use that include rHuPH20 are described in U.S. Patent Application Publication Nos. 2005 / 0260186 and 2006 / 0104968. In one aspect, the sHASEGP is combined with one or more additional glycosaminoglycanases (e.g., chondroitinase).

[0192] Exemplary lyophilized antibody formulations are described in U.S. Patent No. 6,267,958. Aqueous antibody formulations include those described in U.S. Patent No. 6,171,586 and International Publication No. 2006 / 044908, the latter formulation including a histidine acetate buffer.

[0193] The formulations herein may also include more than one active ingredient, as needed for the particular indication being treated, preferably including those having complementary activities that do not adversely affect each other. For example, it may be desirable to further provide additional therapeutic agents (e.g., corticosteroids, antihistamines, antipyretics, chemotherapeutic agents, cytotoxic agents, growth inhibitors, and / or antihormonal agents, such as those mentioned above herein). Such active ingredients are suitably present in combination in an amount effective for the intended purpose.

[0194] The active ingredient may also be incorporated within colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microemulsions, nanoparticles, and nanocapsules) or in macroemulsions, for example, by coacervation techniques or by interfacial polymerization, such as with hydroxy methylcellulose or gelatin microcapsules and poly-(methylmethacrylate) microcapsules, respectively. Such techniques are disclosed in Remington’s Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980).

[0195] Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing antibodies, and these matrices are in the form of molded articles, such as films or microcapsules.

[0196] Formulations for in vivo administration are generally sterile. Sterility can be readily achieved, for example, by filtration through a sterile filtration membrane.

[0197] In some embodiments, mosunetuzumab is formulated for intravenous administration (e.g., intravenous infusion). In some embodiments, dexamethasone is formulated for intravenous administration. In some embodiments, dexamethasone is formulated for intravenous or oral administration. In some embodiments, methylprednisolone is formulated for intravenous or oral administration. In some embodiments, acetaminophen or paracetamol is formulated for oral administration. In some embodiments, diphenhydramine is formulated for oral or intravenous administration.

[0198] VI. Kits and Manufactured Articles In another aspect of the present invention, there is provided a kit or a manufactured article comprising a material useful for the treatment, prevention and / or diagnosis of the above-described disorders. The kit or manufactured article includes a container and a label or package insert on or associated with the container. Suitable containers include, for example, bottles, vials, syringes, IV solution bags, and the like. The container may be formed from various materials such as glass or plastic. The container may hold the composition by itself or in combination with another composition effective for the treatment, prevention, and / or diagnosis of symptoms and may have a sterile access port (for example, the container may be a vial having a stopper pierceable by a hypodermic needle). At least one active agent in the composition is the mosunetuzumab, corticosteroid, antihistamine or antipyretic described herein. The label or package insert indicates that the composition is used for treating selected symptoms (e.g., R / R NHL, e.g., R / R FL, (e.g., R / R FL that is grade 1, 2, 3a but not 3b), R / R trFL or R / R DLBCL) and further includes information regarding at least one of the dosing regimens described herein. Further, the kit or manufactured article may include a first container (a) containing the composition, the composition comprising the anti-CD20 / anti-CD3 bispecific antibody described herein, and a second container (b) containing the composition, the composition comprising a further cytotoxic agent or other therapeutic agent. Alternatively or additionally, the kit or manufactured article may further comprise a second (or third) container containing a pharmaceutically acceptable buffer such as bacteriostatic water for injection (BWFI), phosphate buffered saline, Ringer's solution, and dextrose solution. It may further include other materials desirable from a commercial and user perspective, including other buffers, diluents, filters, needles and syringes.

Example

[0199] The following are examples of the methods of the present invention. It is understood that various other embodiments may be practiced in view of the general description given above.

[0200] Example 1. Mosunetuzumab is effective and well-tolerated in patients with relapsed / refractory (R / R) follicular lymphoma (FL) under 65 years old and 65 years old and above who have had two or more prior treatments: Subgroup analysis of a pivotal Phase II study In this study, the safety, tolerability, and pharmacokinetics of step-up dosing of mosunetuzumab in patients with relapsed or refractory (R / R) follicular lymphoma (FL) under 65 years old and 65 years old and above were compared. All patients had grade (Gr) 1-3a R / R FL and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and were refractory to or had relapsed from two or more prior treatments including anti-CD20 antibodies and alkylating agents. Follicular lymphoma typically develops in elderly patients, who often have a reduced immune function and are more susceptible to treatment-related toxicities than younger patients.

[0201] Methods Patients were administered three escalating doses of 1 mg, 2 mg, and 60 mg of mosunetuzumab in the first dosing cycle, a single dose of 60 mg of mosunetuzumab in the second dosing cycle, and additional single doses of 30 mg of mosunetuzumab in subsequent additional dosing cycles. Figure 1 shows an overview of the study dosing regimen. Specifically, intravenous (IV) mosunetuzumab was administered in 21-day dosing cycles, and the first dosing cycle (cycle 1 (C1)) had a first dose of 1 mg (C1D1 dose) administered on day 1 of cycle 1; a second dose of 2 mg (C1D2 dose) administered on day 8 of cycle 1; and a third dose of 60 mg (C1D3 dose) administered on day 15 of cycle 1; the second dosing cycle (cycle 2) had a first dose of 60 mg (C2D1 dose) administered on day 1 of cycle 2; and the additional dosing cycles (cycle 3+) each had a single dose of 30 mg (C3D1+) administered on day 1 of each additional dosing cycle.

[0202] Corticosteroid premedication (IV dexamethasone 20 mg or IV methylprednisolone 80 mg) was administered 1 hour before each dose of mosunetuzumab in cycles 1 and 2 and was optional from cycle 3 onwards.

[0203] Patients who had a complete response by administration cycle 8 (C8) completed treatment; patients with a partial response or stable disease continued treatment for up to 17 administration cycles (C17) as long as disease progression or unacceptable toxicity did not occur. The primary endpoint was the complete response rate (CR) by positron emission tomography (PET) / computed tomography (CT) (as best response) evaluated by an independent review committee using standard response criteria (Cheson et al. Journal of Clinical Oncology. 25:579 - 586, 2007). Secondary endpoints included objective response rate (ORR), duration of response (DoR), duration of CR (DoCR), progression - free survival (PFS), as well as safety and tolerability. Cytokine release syndrome (CRS) was graded using the ASTCT criteria (Lee et al. Biology of Blood and Marrow Transplantation. 25(4):625 - 638, 2019).

[0204] At the data cutoff (August 27, 2021), mosunetuzumab was administered to 90 patients. Of these, 60 (67%) were younger than 65 years and 30 (33%) were 65 years or older (Table 3).

Table 3

[0205] The median observation period was 18.4 months in patients under 65 years old and 18.1 months in patients 65 years old and above. Among patients under 65 years old, 30 patients completed the initial treatment and 30 patients discontinued the treatment (21 due to progressive disease, 3 due to AE, and 3 for other reasons). Among patients 65 years old and above, 24 patients completed the initial treatment and 6 patients discontinued the treatment (4 due to progressive disease, 1 due to AE, and 1 for other reasons). The median treatment period was 4.9 months in patients under 65 years old and 5.1 months in patients 65 years old and above. For details, please refer to Table 4.

Table 4

[0206] Results of Efficacy In both age subgroups, a high response rate with associated durability was achieved. The complete response rate and objective response rate were high across the study, and numerically higher in patients 65 years old and above than in patients under 65 years old. (Table 5).

Table 5

[0207] A high response rate and durable responses were achieved in both age subgroups, and a 70% CR rate was observed in patients 65 years old and above. The median PFS in patients 65 years old and above was 17.9 months (95% CI: 12.0 - NE), which was very consistent with the PFS reported for the entire study population. The median PFS in patients under 65 years old was 12.0 months (95% CI: 8.4 - NE).

[0208] Results of Pharmacokinetics and Biomarkers The pharmacokinetic profile of mosunetuzumab was comparable across age groups. Age was tested as a continuous variable in a population pharmacokinetic (PK) model and was not found to be significantly associated with mosunetuzumab PK parameters (p>0.05). Exposure (AUC [area under the curve] 0–42 days) was similar between patients <65 years and those ≥65 years.

[0209] Levels of CD20 (dual CD20+PAX5+ based on immunohistochemistry [IHC]), intratumoral T cells (CD8+ IHC), and peripheral T cells, B cells, and natural killer cells (by flow cytometry) were similar at baseline between patients <65 years and those ≥65 years.

[0210] Safety results The rates of all-grade and grade 3 / 4 adverse events (AEs) were comparable across age groups. However, the rate of serious AEs (SAEs) was lower in patients ≥65 years compared with those <65 years (52% vs 37%; Table 6).

Table 6

[0211] Two mosunetuzumab-related neurological AEs (NAEs) potentially consistent with immune effector cell-associated neurotoxicity syndrome (ICANS) were identified in each age subgroup (all NAEs were grade 1 / 2): in patients <65 years: delirium (n = 1; grade 1), attention disorder (n = 1; grade 1); in patients ≥65 years: delirium and cognitive impairment (n = 1; grade 1), delirium (n = 1; grade 2).

[0212] There were no cases of aphasia, seizure, encephalopathy, or cerebral edema.

[0213] The rates of SAEs of neutropenia and infection, which were particularly notable adverse events in the study, were similar across age subgroups (Table 7).

[0214] In patients under 65 years of age, 34 neutropenia events were reported, 97% of which resolved; 20 events were reported in patients 65 years of age and older, and all events resolved. [Table 7]

[0215] Most CRS events were of low grade (less than grade 3 according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria (Lee et al. Biology of Blood and Marrow Transplantation. 25(4):625 - 638, 201), and all resolved. CRS events were numerically less frequent in patients 65 years of age and older compared to those under 65 years of age (30% vs. 52%; Table 8). [Table 8]

[0216] A low rate of discontinuation due to adverse events (AE) was observed. In the subgroup 65 years of age and older, 3% of patients discontinued treatment due to AE, and no treatment - related fatal events were reported.

[0217] Embodiments Some embodiments of the technology described herein can be defined according to any of the following numbered embodiments. 1. A method of treating a subject about 65 years of age or older having relapsed or refractory (R / R) non - Hodgkin lymphoma (NHL), comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle, (a) The first three - dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab, where C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab, where C3D1 is about 30 mg, a method.

[0218] 2. Mosunetuzumab for use in the treatment of subjects about 65 years of age or older having relapsed or refractory (R / R) non-Hodgkin lymphoma (NHL), wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab, where C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab, where C3D1 is about 30 mg, mosunetuzumab for use.

[0219] 3. Use of mosunetuzumab for the treatment of subjects about 65 years of age or older having relapsed or refractory (R / R) non-Hodgkin lymphoma (NHL), wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab, where C2D1 is about 60 mg; and (c) Use, wherein the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab, and C3D1 is about 30 mg.

[0220] 4. Use of mosunetuzumab in the manufacture of a medicament for use in treating subjects about 65 years of age or older having relapsed or refractory (R / R) non-Hodgkin lymphoma (NHL), wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab, where C2D1 is about 60 mg; and (c) Use, wherein the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab, and C3D1 is about 30 mg.

[0221] 5. The method according to any one of embodiments 1 to 4, the mosunetuzumab for use, or the use, wherein the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

[0222] 6. The method according to embodiment 5, the mosunetuzumab for use, or the use, wherein two or more prior treatment lines comprise an anti-CD20 monoclonal antibody, an alkylating agent, or both an anti-CD20 monoclonal antibody and an alkylating agent.

[0223] 7. The method according to any one of embodiments 1 to 6, the mosunetuzumab for use, or the use, wherein the R / R NHL is R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL).

[0224] 8. The method, mosunetuzumab for use, or use according to embodiment 7, wherein the R / R NHL is R / R FL.

[0225] 9. The method, mosunetuzumab for use, or use according to embodiment 8, wherein the R / R FL is histologically demonstrated to be grade 1, 2 or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90), but not 3b.

[0226] 10. The method, mosunetuzumab for use, or use according to any one of embodiments 1-9, wherein the first, second, and third dosing cycles are each 21-day dosing cycles.

[0227] 11. The method according to any one of embodiments 1 and 5-10, comprising administering C1D1, C1D2, and C1D3 on days 1, 8, and 15, respectively, of the first dosing cycle.

[0228] 12. The method according to any one of embodiments 1 and 5-11, comprising administering C2D1 on day 1 of the second dosing cycle.

[0229] 13. The method according to any one of embodiments 1 and 5-12, comprising administering C3D1 on day 1 of the third dosing cycle.

[0230] 14. The mosunetuzumab for use or use according to any one of embodiments 2-10, wherein C1D1, C1D2, and C1D3 are to be administered to the subject on days 1, 8, and 15, respectively, of the first dosing cycle.

[0231] 15. The mosunetuzumab for use or use according to any one of embodiments 2-10 and 14, wherein C2D1 is to be administered to the subject on day 1 of the second dosing cycle.

[0232] For use according to any one of embodiments 2 to 10, 14, and 15, wherein C3D1 is to be administered to a subject on day 1 of a third dosing cycle, the use of mosunetuzumab or the use.

[0233] 17. The method according to any one of embodiments 1 to 16, the use of mosunetuzumab for use, or the use, wherein the dosing regimen further comprises one or more additional dosing cycles.

[0234] 18. The method according to embodiment 17, the use of mosunetuzumab for use, or the use, wherein the dosing regimen comprises 5 to 14 additional dosing cycles.

[0235] 19. The method according to embodiment 18, the use of mosunetuzumab for use, or the use, wherein the dosing regimen comprises 5 additional dosing cycles.

[0236] 20. The method according to embodiment 19, the use of mosunetuzumab for use, or the use, wherein the dosing regimen comprises 14 additional dosing cycles.

[0237] 21. The method according to any one of embodiments 17 to 20, the use of mosunetuzumab for use, or the use, wherein each of the one or more additional dosing cycles is a 21-day dosing cycle.

[0238] 22. The method according to any one of embodiments 17 to 21, the use of mosunetuzumab for use, or the use, wherein each of the one or more additional dosing cycles comprises an additional single dose of mosunetuzumab.

[0239] 23. The method according to embodiment 22, the use of mosunetuzumab for use, or the use, wherein the additional single dose of mosunetuzumab is to be administered or is to be administered to the subject on day 1 of each additional dosing cycle.

[0240] 24. The method according to embodiment 22 or 23, the use of mosunetuzumab for use, or the use, wherein the additional single dose of mosunetuzumab is about 30 mg.

[0241] 25. The method according to any one of embodiments 1 to 24, the mosunetuzumab for use, or the use, wherein the mosunetuzumab is administered or is to be administered by intravenous injection.

[0242] 26. A method of treating a population of subjects about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) the third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, wherein C3D1 is about 30 mg.

[0243] 27. Mosunetuzumab for use in the treatment of a population of subjects about 65 years of age or older having R / R NHL, wherein the mosunetuzumab is to be intravenously administered to each subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) the first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab that is to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab that is to be administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, for use of mosunetuzumab.

[0244] 28. Use of mosunetuzumab for treating a population of subjects about 65 years of age or older having R / R NHL, wherein mosunetuzumab is to be administered intravenously to each subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab that are to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab that is to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab that is to be administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, for use.

[0245] 29. Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of a population of subjects about 65 years of age or older having R / R NHL, wherein mosunetuzumab is to be administered intravenously to each subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose administration cycle includes the first dose (C1D1), the second dose (C1D2), and the third dose (C1D3) of mosunetuzumab, which are to be administered on the 1st, 8th, and 15th days of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab, which is to be administered on the 1st day of the second administration cycle, where C2D1 is about 60 mg; and (c) The third administration cycle includes a single dose (C3D1) of mosunetuzumab, which is to be administered on the 1st day of the third administration cycle, where C3D1 is about 30 mg, for use.

[0246] A method of treating a population of subjects about 65 years of age or older with relapsed / refractory (R / R) NHL, comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 8 twenty-one-day administration cycles, (a) The first three-dose administration cycle includes the first dose (C1D1), the second dose (C1D2), and the third dose (C1D3) of mosunetuzumab, which are to be administered on the 1st, 8th, and 15th days of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab, which is to be administered on the 1st day of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to eighth administration cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab, which are to be administered on the 1st day of each administration cycle, where each of C3D1 - C8D1 is about 30 mg, a method.

[0247] Mosunetuzumab for use in the treatment of a population of subjects about 65 years of age or older with relapsed / refractory (R / R) NHL, wherein mosunetuzumab is to be intravenously administered to each subject in a dosing regimen comprising 8 twenty-one-day administration cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to eighth administration cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C8D1 is about 30 mg, for use of mosunetuzumab.

[0248] Use of mosunetuzumab for treating a population of subjects about 65 years of age or older having R / R NHL, wherein mosunetuzumab is to be administered intravenously to each subject in a dosing regimen comprising 8 twenty - one - day administration cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to eighth administration cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C8D1 is about 30 mg, the use.

[0249] Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of a population of subjects aged about 65 years or older having relapsed / refractory (R / R) non-Hodgkin lymphoma (NHL), wherein mosunetuzumab is to be administered intravenously to each subject in a dosing regimen comprising 8 cycles of administration of 21 days each, (a) a first 3-dose cycle of administration comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15, respectively, of the first cycle of administration, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second cycle of administration comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second cycle of administration, wherein C2D1 is about 60 mg; and (c) the third to eighth cycles of administration each comprising a single dose (C3D1-C8D1) of mosunetuzumab to be administered on day 1 of each cycle of administration, wherein each of C3D1-C8D1 is about 30 mg.

[0250] A method of treating a population of subjects aged about 65 years or older having R / R NHL, comprising administering mosunetuzumab intravenously to each subject in a dosing regimen comprising 17 cycles of administration of 21 days each, (a) a first 3-dose cycle of administration comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15, respectively, of the first cycle of administration, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second cycle of administration comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second cycle of administration, wherein C2D1 is about 60 mg; and (c) the third to seventeenth cycles of administration each comprising a single dose (C3D1-C17D1) of mosunetuzumab to be administered on day 1 of each cycle of administration, wherein each of C3D1-C17D1 is about 30 mg.

[0251] Mosunetuzumab for use in the treatment of a population of subjects aged about 65 years or older with relapsed / refractory (R / R) NHL, wherein mosunetuzumab is to be administered intravenously to each subject in a dosing regimen comprising 17 cycles of 21-day dosing cycles, (a) a first 3-dose dosing cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second dosing cycle comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) the third to seventeenth dosing cycles each comprising a single dose (C3D1-C17D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, wherein each of C3D1-C17D1 is about 30 mg, mosunetuzumab for use.

[0252] The use of mosunetuzumab for treating a population of subjects aged about 65 years or older with relapsed / refractory (R / R) NHL, wherein mosunetuzumab is to be administered intravenously to each subject in a dosing regimen comprising 17 cycles of 21-day dosing cycles, (a) a first 3-dose dosing cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second dosing cycle comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) the third to seventeenth dosing cycles each comprising a single dose (C3D1-C17D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, wherein each of C3D1-C17D1 is about 30 mg, the use.

[0253] Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of a population of subjects aged about 65 years or older with relapsed / refractory (R / R) non-Hodgkin lymphoma (NHL), wherein mosunetuzumab is to be administered intravenously to each subject in a dosing regimen comprising 17 cycles of 21-day dosing, (a) a first three-dose dosing cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second dosing cycle comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) the third to seventeenth dosing cycles each comprising a single dose (C3D1-C17D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, wherein each of C3D1-C17D1 is about 30 mg.

[0254] 38. The method, mosunetuzumab for use, or use according to any one of embodiments 26-37, wherein each subject in the population of subjects has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0255] 39. The method, mosunetuzumab for use, or use according to embodiment 38, wherein the two or more prior lines of therapy comprise an anti-CD20 monoclonal antibody, an alkylating agent, or both an anti-CD20 monoclonal antibody and an alkylating agent.

[0256] 40. The method, mosunetuzumab for use, or use according to any one of embodiments 26-39, wherein the R / R NHL is R / R follicular lymphoma (FL), R / R transformed follicular lymphoma (trFL), or R / R diffuse large B-cell lymphoma (DLBCL).

[0257] 41. The method, mosunetuzumab for use, or use according to embodiment 40, wherein the R / R NHL is R / R FL.

[0258] 42. The method, mosunetuzumab for use, or use according to embodiment 41, wherein the R / R FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization lymphoid neoplasm classification (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90), but not 3b.

[0259] 43. The method, mosunetuzumab for use, or use according to any one of embodiments 26-42, wherein mosunetuzumab is administered or is to be administered by intravenous infusion.

[0260] 44. The method, mosunetuzumab for use, or use according to any one of embodiments 26-43, wherein the objective response rate in the population of subjects is 65% or more.

[0261] 45. The method, mosunetuzumab for use, or use according to embodiment 44, wherein the objective response rate in the population of subjects is 75% or more.

[0262] 46. The method, mosunetuzumab for use, or use according to embodiment 45, wherein the objective response rate in the population of subjects is 85% or more.

[0263] 47. The method, mosunetuzumab for use, or use according to any one of embodiments 26-43, wherein the complete response rate in the population of subjects is 50% or more.

[0264] 48. The method, mosunetuzumab for use, or use according to embodiment 47, wherein the complete response rate in the population of subjects is 60% or more.

[0265] 49. The method, mosunetuzumab for use, or use according to embodiment 48, wherein the complete response rate in the population of subjects is 70% or more.

[0266] 50. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein 40% or more of the subjects having an objective response maintained remission for 18 months.

[0267] 51. The method, mosunetuzumab for use, or use according to embodiment 50, wherein 50% or more of the subjects having an objective response maintained remission for 18 months.

[0268] 52. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein 50% or more of the subjects having a complete response maintained complete remission for 18 months.

[0269] 53. The method, mosunetuzumab for use, or use according to embodiment 52, wherein 60% or more of the subjects having a complete response maintained complete remission for 18 months.

[0270] 54. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein the median duration of response in the population of subjects is 9 months or more.

[0271] 55. The method, mosunetuzumab for use, or use according to embodiment 54, wherein the median duration of response in the population of subjects is 15 months or more.

[0272] 56. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein the median duration of complete response in the population of subjects is 12 months or more.

[0273] 57. The method according to embodiment 56, wherein the median duration of complete response in the population of subjects is 16 months or more.

[0274] 58. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein 35% or more of the subjects have progression-free survival of 18 months.

[0275] 59. The method, mosunetuzumab for use, or use according to embodiment 58, wherein more than 45% of the subjects have progression-free survival of 18 months.

[0276] 60. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein the median progression-free survival in the population of subjects is 12 months or more.

[0277] 61. The method, mosunetuzumab for use, or use according to embodiment 60, wherein the median progression-free survival in the population of subjects is 17 months or more.

[0278] 62. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein the percentage of severe adverse events excluding grade 5 malignant neoplasm progression in the population of subjects is 45% or less.

[0279] 63. The method, mosunetuzumab for use, or use according to embodiment 62, wherein the percentage of severe adverse events excluding grade 5 malignant neoplasm progression in the population of subjects is 40% or less.

[0280] 64. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein the percentage of severe adverse events related to mosunetuzumab in the population of subjects is 40% or less.

[0281] 65. The method, mosunetuzumab for use, or use according to embodiment 64, wherein the percentage of severe adverse events related to mosunetuzumab in the population of subjects is 30% or less.

[0282] 66. The method, mosunetuzumab for use, or use according to any one of embodiments 26 to 43, wherein the percentage of cytokine release syndrome of grade 3 or higher (defined by the American Society for Transplantation and Cellular Therapy, 2018; ASTCT) in the population of subjects is 5% or less.

[0283] 67. The method according to embodiment 66, the mosunetuzumab for use, or the use, wherein the proportion of cytokine release syndrome having grade 3 or higher (as defined by ASTCT) in the target population is 3% or less.

[0284] 68. The method according to any one of embodiments 26 to 43, the mosunetuzumab for use, or the use, wherein the proportion of cytokine release syndrome of any grade (as defined by ASTCT) in the target population is 40% or less.

[0285] 69. The method according to embodiment 68, the mosunetuzumab for use, or the use, wherein the proportion of cytokine release syndrome of any grade (as defined by ASTCT) in the target population is 30% or less.

[0286] 70. A method for achieving objective response, complete response or progression-free survival in a subject about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first 3-dose administration cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg.

[0287] Mosunetuzumab for use in achieving objective response, complete response or progression-free survival in subjects about 65 years of age or older with R / R NHL, to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab to be administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, mosunetuzumab for use.

[0288] Use of mosunetuzumab to achieve objective response, complete response or progression-free survival in subjects about 65 years of age or older with R / R NHL, to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) Use, wherein the third dosing cycle comprises a single dose of mosunetuzumab (C3D1) to be administered on day 1 of the third dosing cycle, and C3D1 is about 30 mg.

[0289] 73. Use of mosunetuzumab in the manufacture of a medicament for use in achieving objective response, complete response or progression-free survival in a subject of about 65 years of age or older having R / R NHL, wherein the subject is to be administered intravenously in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose dosing cycle comprises a first dose of mosunetuzumab (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose of mosunetuzumab (C2D1) to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) Use, wherein the third dosing cycle comprises a single dose of mosunetuzumab (C3D1) to be administered on day 1 of the third dosing cycle, and C3D1 is about 30 mg.

[0290] 74. A method of achieving objective response, complete response or progression-free survival in a subject of about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising eight 21-day dosing cycles, (a) The first three-dose dosing cycle comprises a first dose of mosunetuzumab (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third to eighth dosing cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, where each of C3D1 - C8D1 is about 30 mg, a method.

[0291] 75. Mosunetuzumab for use in achieving objective response, complete response or progression - free survival in subjects about 65 years of age or older with R / R NHL, to be administered intravenously to the subject in a dosing regimen comprising 8 twenty - one - day dosing cycles, (a) The first three - dose dosing cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third to eighth dosing cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, where each of C3D1 - C8D1 is about 30 mg, mosunetuzumab for use.

[0292] 76. Use of mosunetuzumab to achieve objective response, complete response or progression - free survival in subjects about 65 years of age or older with R / R NHL, to be administered intravenously to the subject in a dosing regimen comprising 8 twenty - one - day dosing cycles, (a) The first three - dose dosing cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose (C2D1) of mosunetuzumab that is to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third to eighth dosing cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab that is to be administered on day 1 of each dosing cycle, where each of C3D1 - C8D1 is about 30 mg, use.

[0293] 77. Use of mosunetuzumab in the manufacture of a medicament for use in achieving objective response, complete response or progression - free survival in a subject of about 65 years of age or older having R / R NHL, to be intravenously administered to the subject in a dosing regimen comprising 8 twenty - one - day dosing cycles, (a) The first three - dose dosing cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab that are to be administered on days 1, 8, and 15 of the first dosing cycle respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose (C2D1) of mosunetuzumab that is to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third to eighth dosing cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab that are to be administered on day 1 of each dosing cycle, where each of C3D1 - C8D1 is about 30 mg, use.

[0294] 78. A method of achieving objective response, complete response or progression - free survival in a subject of about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty - one - day dosing cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, a method.

[0295] Mosunetuzumab for use in achieving objective response, complete response, or progression-free survival in subjects about 65 years of age or older with R / R NHL, to be intravenously administered to the subject in a dosing regimen comprising 17 twenty-one-day administration cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, mosunetuzumab for use.

[0296] The use of mosunetuzumab to achieve objective response, complete response or progression-free survival in subjects aged about 65 years or older with relapsed / refractory (R / R) NHL, wherein the subject is to be administered intravenously according to a dosing regimen comprising 17 twenty-one-day dosing cycles, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third to seventeenth dosing cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, wherein each of C3D1 - C17D1 is about 30 mg.

[0297] The use of mosunetuzumab in the manufacture of a medicament for use in achieving objective response, complete response or progression-free survival in subjects aged about 65 years or older with relapsed / refractory (R / R) NHL, wherein the subject is to be administered intravenously according to a dosing regimen comprising 17 twenty-one-day dosing cycles, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third to seventeenth dosing cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, wherein each of C3D1 - C17D1 is about 30 mg.

[0298] 82. The method, mosunetuzumab for use, or use according to any one of embodiments 70 to 81, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0299] 83. The method, mosunetuzumab for use, or use according to embodiment 82, wherein the two or more prior lines of therapy include an anti-CD20 monoclonal antibody, an alkylating agent, or both an anti-CD20 monoclonal antibody and an alkylating agent.

[0300] 84. The method, mosunetuzumab for use, or use according to any one of embodiments 70 to 83, wherein the R / R NHL is R / R FL, R / R trFL, or R / R DLBCL.

[0301] 85. The method, mosunetuzumab for use, or use according to embodiment 84, wherein the R / R NHL is R / R FL.

[0302] 86. The method, mosunetuzumab for use, or use according to embodiment 85, wherein the R / R FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90), but not 3b.

[0303] 87. The method, mosunetuzumab for use, or use according to any one of embodiments 70 to 86, wherein mosunetuzumab is administered or is to be administered by intravenous infusion.

[0304] 88. The method, mosunetuzumab for use, or use according to any one of embodiments 70 to 87, wherein the subject achieves an objective response.

[0305] 89. The method, mosunetuzumab for use, or use according to any one of embodiments 70 to 87, wherein the subject achieves complete response.

[0306] 90. The method, mosunetuzumab for use, or use according to any one of embodiments 70 to 87, wherein progression-free survival is maintained for 12 months or more.

[0307] 91. The method, mosunetuzumab for use, or use according to embodiment 90, wherein progression-free survival is maintained for 18 months or more.

[0308] 92. The method, mosunetuzumab for use, or use according to any one of embodiments 1 to 91, further comprising: (a) administering one or more additional therapeutic agents to the subject or each subject in the population of subjects; (b) mosunetuzumab will be administered to the subject or each subject in the population of subjects in combination with one or more additional therapeutic agents; or (c) the medicament is formulated for administration to the subject or each subject in the population of subjects in combination with one or more additional therapeutic agents, method, mosunetuzumab for use, or use.

[0309] 93. The method, mosunetuzumab for use, or use according to embodiment 92, wherein one or more additional therapeutic agents comprise tocilizumab.

[0310] 94. The method, mosunetuzumab for use, or use according to embodiment 92 or 93, wherein one or more additional therapeutic agents comprise a corticosteroid.

[0311] 95. The method, mosunetuzumab for use, or use according to embodiment 94, wherein the corticosteroid comprises dexamethasone or methylprednisolone.

[0312] 96. The method, mosunetuzumab for use, or use according to embodiment 94 or 95, wherein corticosteroid is administered, or is to be administered, to the subject or each subject in the population of subjects at least 1 hour prior to administration of any dose of mosunetuzumab.

[0313] 97. The method, mosunetuzumab for use, or use according to any one of embodiments 94 - 96, wherein corticosteroid is administered, or is to be administered, only during administration cycle 1 or administration cycle 2.

[0314] 98. The method, mosunetuzumab for use, or use according to any one of embodiments 94 - 97, wherein corticosteroid is administered, or is to be administered, intravenously.

[0315] 99. The method, mosunetuzumab for use, or use according to any one of embodiments 94 - 98, wherein corticosteroid comprises dexamethasone and is administered, or is to be administered, at a dose of about 20 mg.

[0316] 100. The method, mosunetuzumab for use, or use according to any one of embodiments 94 - 98, wherein corticosteroid comprises methylprednisolone and is administered, or is to be administered, at a dose of about 80 mg.

[0317] 101. The method, mosunetuzumab for use, or use according to any one of embodiments 92 - 100, wherein the one or more additional therapeutic agents comprise an antihistamine.

[0318] 102. The method, mosunetuzumab for use, or use according to embodiment 101, wherein the antihistamine is administered, or is to be administered, to the subject or each subject in the population of subjects at least 30 minutes prior to administration of any dose of mosunetuzumab.

[0319] 103. The method, mosunetuzumab for use, or use according to embodiment 101 or 102, wherein the antihistamine is administered only during dosing cycle 1 or dosing cycle 2, or is to be administered.

[0320] 104. The method, mosunetuzumab for use, or use according to any one of embodiments 101 to 103, wherein the antihistamine is administered orally or intravenously, or is to be administered.

[0321] 105. The method, mosunetuzumab for use, or use according to any one of embodiments 101 to 104, wherein the antihistamine comprises diphenhydramine hydrochloride and is administered at a dose of about 50 - 100 mg, or is to be administered.

[0322] 106. The method, mosunetuzumab for use, or use according to any one of embodiments 92 to 105, wherein one or more additional therapeutic agents comprise an antipyretic.

[0323] 107. The method, mosunetuzumab for use, or use according to embodiment 106, wherein the antipyretic is administered to the subject or each subject in the population of subjects at least 30 minutes prior to the administration of any dose of mosunetuzumab, or is to be administered.

[0324] 108. The method, mosunetuzumab for use, or use according to embodiment 106 or 107, wherein the antipyretic is administered only during dosing cycle 1 or dosing cycle 2, or is to be administered.

[0325] 109. The method, mosunetuzumab for use, or use according to any one of embodiments 106 to 108, wherein the antipyretic is administered orally, or is to be administered.

[0326] 110. The method, mosunetuzumab for use, or use according to any one of embodiments 106 to 109, wherein the antipyretic comprises acetaminophen and is administered at a dose of about 500 - 1000 mg.

[0327] A method for treating a subject aged about 65 years or older with relapsed / refractory (R / R) NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, The method, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0328] Mosunetuzumab for use in the treatment of a subject aged about 65 years or older with R / R NHL, wherein mosunetuzumab is to be intravenously administered to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle includes a single dose (C3D1) of mosunetuzumab to be administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, Mosunetuzumab for use, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0329] 113. Use of mosunetuzumab for the treatment of a subject of about 65 years of age or older having R / R NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose dosing cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle includes a single dose (C3D1) of mosunetuzumab to be administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, Use, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0330] 114. Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of a subject of about 65 years of age or older having R / R NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose administration cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third administration cycle includes a single dose (C3D1) of mosunetuzumab to be administered on day 1 of the third administration cycle, where C3D1 is about 30 mg, Use in a subject who has relapsed after two or more prior lines of therapy or who is refractory to two or more prior lines of therapy.

[0331] 115. A method of treating a subject about 65 years of age or older with R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 twenty-one-day administration cycles, (a) The first three-dose administration cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to eighth administration cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C8D1 is about 30 mg, A method in a subject who has relapsed after two or more prior lines of therapy or who is refractory to two or more prior lines of therapy.

[0332] Moxetumomab for use in the treatment of subjects about 65 years of age or older with relapsed / refractory (R / R) NHL, wherein moxetumomab is to be administered intravenously to the subject in a dosing regimen that includes 8 cycles of 21-day administrations, (a) a first 3-dose administration cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of moxetumomab to be administered on days 1, 8, and 15, respectively, of the first administration cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second administration cycle comprising a single dose (C2D1) of moxetumomab to be administered on day 1 of the second administration cycle, wherein C2D1 is about 60 mg; and (c) the third through eighth administration cycles each comprising a single dose (C3D1 - C8D1) of moxetumomab to be administered on day 1 of each administration cycle, wherein each of C3D1 - C8D1 is about 30 mg, moxetumomab for use, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0333] Use of moxetumomab for the treatment of subjects about 65 years of age or older with R / R NHL, wherein moxetumomab is to be administered intravenously to the subject in a dosing regimen that includes 8 cycles of 21-day administrations, (a) a first 3-dose administration cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of moxetumomab to be administered on days 1, 8, and 15, respectively, of the first administration cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second administration cycle comprising a single dose (C2D1) of moxetumomab to be administered on day 1 of the second administration cycle, wherein C2D1 is about 60 mg; and (c) The 3rd to 8th dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C8D1) to be administered on the first day of each dosing cycle, with each of C3D1 - C8D1 being approximately 30 mg, Use in a subject who has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

[0334] Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of a subject of about 65 years of age or older having R / R NHL, wherein the mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 8 twenty - one - day dosing cycles, (a) The first 3 - dose dosing cycle contains the first dose (C1D1), the second dose (C1D2), and the third dose (C1D3) of mosunetuzumab to be administered on the first day, eighth day, and fifteenth day of the first dosing cycle respectively, with C1D1 being approximately 1 mg, C1D2 being approximately 2 mg, and C1D3 being approximately 60 mg; (b) The second dosing cycle contains a single dose of mosunetuzumab (C2D1) to be administered on the first day of the second dosing cycle, with C2D1 being approximately 60 mg; and (c) The 3rd to 8th dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C8D1) to be administered on the first day of each dosing cycle, with each of C3D1 - C8D1 being approximately 30 mg, Use in a subject who has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

[0335] A method of treating a subject of about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty - one - day dosing cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, A method, wherein the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

[0336] Mosunetuzumab for use in the treatment of subjects about 65 years of age or older with R / R NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 twenty-one-day administration cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, Mosunetuzumab for use, wherein the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

[0337] Use of mosunetuzumab for the treatment of subjects aged about 65 years or older with relapsed / refractory (R / R) NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 cycles of 21-day administrations, (a) the first 3-dose administration cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first administration cycle, respectively, with C1D1 being about 1 mg, C1D2 being about 2 mg, and C1D3 being about 60 mg; (b) the second administration cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, with C2D1 being about 60 mg; and (c) the third to seventeenth administration cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, with each of C3D1 - C17D1 being about 30 mg, for use in a subject who has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0338] Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of subjects aged about 65 years or older with R / R NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 cycles of 21-day administrations, (a) the first 3-dose administration cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first administration cycle, respectively, with C1D1 being about 1 mg, C1D2 being about 2 mg, and C1D3 being about 60 mg; (b) the second administration cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, with C2D1 being about 60 mg; and (c) The 3rd to 17th dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C17D1) to be administered on the first day of each dosing cycle, with each of C3D1 - C17D1 being approximately 30 mg, Use in a subject who has relapsed after two or more prior lines of therapy or who is refractory to two or more prior lines of therapy.

[0339] A method of treating a subject about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21 - day dosing cycle, a second 21 - day dosing cycle, and a third 21 - day dosing cycle, (a) The first 3 - dose dosing cycle contains a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on the first, eighth, and fifteenth days of the first dosing cycle, respectively, with C1D1 being approximately 1 mg, C1D2 being approximately 2 mg, and C1D3 being approximately 60 mg; (b) The second dosing cycle contains a single dose of mosunetuzumab (C2D1) to be administered on the first day of the second dosing cycle, with C2D1 being approximately 60 mg; and (c) The third dosing cycle contains a single dose of mosunetuzumab (C3D1) to be administered on the first day of the third dosing cycle, with C3D1 being approximately 30 mg, The subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) Administering a corticosteroid, wherein a single dose of corticosteroid is administered to the subject at least 1 hour before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) Administering an anti - histamine, wherein a single dose of anti - histamine is administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic agent, wherein a single dose of the antipyretic agent is administered to the subject at least 30 minutes prior to each of the administrations of Mosunetuzumab at C1D1, C1D2, C1D3, and C2D1, the method comprising:

[0340] Mosunetuzumab for use in the treatment of subjects about 65 years of age or older with R / R NHL, wherein Mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first 3-dose administration cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of Mosunetuzumab to be administered on days 1, 8, and 15 of the first administration cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of Mosunetuzumab to be administered on day 1 of the second administration cycle, wherein C2D1 is about 60 mg; and (c) The third administration cycle comprises a single dose (C3D1) of Mosunetuzumab to be administered on day 1 of the third administration cycle, wherein C3D1 is about 30 mg, The subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) administration of a corticosteroid, wherein a single dose of the corticosteroid is to be administered to the subject at least 1 hour prior to each of the administrations of Mosunetuzumab at C1D1, C1D2, C1D3, and C2D1; (ii) administration of an antihistamine, wherein a single dose of the antihistamine is to be administered to the subject at least 30 minutes prior to each of the administrations of Mosunetuzumab at C1D1, C1D2, C1D3, and C2D1; and / or (iii) Administration of an antipyretic agent, wherein a single dose of the antipyretic agent is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, the administration of the antipyretic agent, Mosunetuzumab for use,

[0341] Use of mosunetuzumab for the treatment of subjects about 65 years of age or older with 125.R / R NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen that includes at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first 3-dose dosing cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, which are to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose (C2D1) of mosunetuzumab, which is to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle includes a single dose (C3D1) of mosunetuzumab, which is to be administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, The subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines, and the dosing regimen further includes (i) Administration of a corticosteroid, wherein a single dose of the corticosteroid is to be administered to the subject at least 1 hour before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, the administration of the corticosteroid; (ii) Administration of an antihistamine, wherein a single dose of the antihistamine is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, the administration of the antihistamine; and / or (iii) Administration of an antipyretic agent, wherein a single dose of the antipyretic agent is to be administered to the subject at least 30 minutes prior to each of the administrations of Mosunetuzumab at C1D1, C1D2, C1D3, and C2D1, the use comprising the administration of the antipyretic agent.

[0342] 126. Use of Mosunetuzumab in the manufacture of a medicament for use in the treatment of a subject about 65 years of age or older having R / R NHL, wherein Mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) A first 3-dose dosing cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of Mosunetuzumab, which are to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) A second dosing cycle comprising a single dose (C2D1) of Mosunetuzumab, which is to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) A third dosing cycle comprising a single dose (C3D1) of Mosunetuzumab, which is to be administered on day 1 of the third dosing cycle, wherein C3D1 is about 30 mg, the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) Administration of a corticosteroid, wherein a single dose of the corticosteroid is to be administered to the subject at least 1 hour prior to each of the administrations of Mosunetuzumab at C1D1, C1D2, C1D3, and C2D1, the administration of the corticosteroid; (ii) Administration of an antihistamine, wherein a single dose of the antihistamine is to be administered to the subject at least 30 minutes prior to each of the administrations of Mosunetuzumab at C1D1, C1D2, C1D3, and C2D1, the administration of the antihistamine; and / or (iii) Administration of an antipyretic agent, wherein a single dose of the antipyretic agent is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3 and C2D1 of mosunetuzumab, the use comprising the administration of the antipyretic agent.

[0343] 127. A method of treating a subject about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days each, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third through eighth dosing cycles each comprise a single dose (C3D1-C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, wherein each of C3D1-C8D1 is about 30 mg, the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is to be administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3 and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3 and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic agent, wherein a single dose of the antipyretic agent is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3 and C2D1 of mosunetuzumab, the method comprising the same.

[0344] Ofatumumab for use in the treatment of subjects aged about 65 years or older with 128.R / R NHL, wherein ofatumumab is to be administered intravenously to the subject in a dosing regimen comprising 8 cycles of 21-day dosing, (a) a first 3-dose dosing cycle comprising ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second dosing cycle comprising a single dose (C2D1) of ofatumumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) the third through eighth dosing cycles each comprising a single dose (C3D1-C8D1) of ofatumumab to be administered on day 1 of each dosing cycle, wherein each of C3D1-C8D1 is about 30 mg, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) administration of a corticosteroid, wherein a single dose of the corticosteroid is to be administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab, (ii) administration of an antihistamine, wherein a single dose of the antihistamine is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab; and / or (iii) administration of an antipyretic, wherein a single dose of the antipyretic is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab, ofatumumab for use.

[0345] Use of mosunetuzumab for the treatment of subjects aged about 65 years or older with relapsed / refractory (R / R) NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 8 cycles of 21-day dosing, (a) a first 3-dose cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second cycle comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second cycle, wherein C2D1 is about 60 mg; and (c) the third to eighth cycles each comprising a single dose (C3D1-C8D1) of mosunetuzumab to be administered on day 1 of each cycle, wherein each of C3D1-C8D1 is about 30 mg, the subject has relapsed after 2 or more prior lines of therapy or is refractory to 2 or more prior lines of therapy, and the dosing regimen further comprises (i) administration of a corticosteroid, wherein a single dose of corticosteroid is to be administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administration of an antihistamine, wherein a single dose of antihistamine is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administration of an antipyretic, wherein a single dose of antipyretic is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab,

[0346] Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of subjects aged about 65 years or older with 130.R / R NHL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 8 dosing cycles of 21 days each, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, wherein each of C3D1 - C8D1 is about 30 mg, The subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) Administration of a corticosteroid, wherein a single dose of corticosteroid is to be administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, (ii) Administration of an antihistamine, wherein a single dose of antihistamine is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) Administration of an antipyretic, wherein a single dose of antipyretic is to be administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, the use comprising.

[0347] A method of treating a subject aged about 65 years or older with relapsed / refractory (R / R) NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty-one-day dosing cycles, (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) the second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) the third to seventeenth dosing cycles each comprise a single dose (C3D1 - C17D1) of mosunetuzumab administered on day 1 of each dosing cycle, wherein each of C3D1 - C17D1 is about 30 mg, the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of corticosteroid is administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, wherein a single dose of antihistamine is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, wherein a single dose of antipyretic is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, the method comprising.

[0348] Mosunetuzumab for use in the treatment of a subject aged about 65 years or older with R / R NHL, wherein mosunetuzumab is to be intravenously administered to the subject in a dosing regimen comprising 17 twenty-one-day dosing cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, The subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines, and the dosing regimen further (i) Administration of a corticosteroid, where a single dose of the corticosteroid is to be administered to the subject at least 1 hour before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) Administration of an antihistamine, where a single dose of the antihistamine is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) Administration of an antipyretic, where a single dose of the antipyretic is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, comprising mosunetuzumab for use.

[0349] Use of mosunetuzumab for the treatment of subjects about 65 years of age or older with R / R NHL, where mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 twenty - one - day administration cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, The subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines, and the dosing regimen further (i) Administration of a corticosteroid, where a single dose of corticosteroid is to be administered to the subject at least 1 hour before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) Administration of an antihistamine, where a single dose of antihistamine is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) Administration of an antipyretic, where a single dose of antipyretic is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, including the use.

[0350] Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of a subject about 65 years of age or older having R / R NHL, where mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 twenty - one - day administration cycles, (a) The first three-dose administration cycle includes the first dose (C1D1), the second dose (C1D2), and the third dose (C1D3) of mosunetuzumab, which are to be administered on the 1st, 8th, and 15th days of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab, which is to be administered on the 1st day of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab, which are to be administered on the 1st day of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, where the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines, and the dosing regimen further includes (i) administration of a corticosteroid, where a single dose of corticosteroid is to be administered to the subject at least 1 hour before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administration of an antihistamine, where a single dose of antihistamine is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administration of an antipyretic, where a single dose of antipyretic is to be administered to the subject at least 30 minutes before each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, including the use.

[0351] 135. The method according to any one of embodiments 111 - 134, the use of mosunetuzumab for use, or the use, where two or more prior treatment lines include an anti - CD20 monoclonal antibody, an alkylating agent, or both an anti - CD20 monoclonal antibody and an alkylating agent.

[0352] The method according to any one of embodiments 111 to 135, wherein the R / R NHL is R / R FL, R / R trFL or R / R DLBCL.

[0353] The method according to embodiment 136, the use of mosunetuzumab for use, or the use, wherein the R / R NHL is R / R FL.

[0354] The method according to embodiment 137, the use of mosunetuzumab for use, or the use, wherein the R / R FL is histologically demonstrated to be grade 1, 2 or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90), but not 3b.

[0355] The method according to any one of embodiments 111 to 138, the use of mosunetuzumab for use, or the use, wherein mosunetuzumab is administered or is to be administered by intravenous infusion.

[0356] The method according to any one of embodiments 123 to 139, the use of mosunetuzumab for use, or the use, (i) A single dose of corticosteroid is administered or is to be administered prior to the administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle; (ii) A single dose of antihistamine is administered or is to be administered prior to the administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle; and / or (iii) A single dose of antipyretic is administered or is to be administered prior to the administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle, the method, the use of mosunetuzumab for use, or the use.

[0357] The method, mosunetuzumab for use, or use according to any one of embodiments 123 to 140, wherein (i) corticosteroid is administered or to be administered intravenously; (ii) antihistamine is administered or to be administered orally or intravenously; and / or (iii) antipyretic is administered or to be administered orally, the method, mosunetuzumab for use, or use.

[0358] The method, mosunetuzumab for use, or use according to any one of embodiments 123 to 141, wherein (i) corticosteroid contains dexamethasone and is administered or to be administered at a dose of about 20 mg, or corticosteroid contains methylprednisolone and is administered or to be administered at a dose of about 80 mg; (ii) antihistamine contains diphenhydramine hydrochloride and is administered or to be administered at a dose of about 50 - 100 mg; and / or (iii) antipyretic contains acetaminophen and is administered or to be administered at a dose of about 500 - 1000 mg, the method, mosunetuzumab for use, or use.

[0359] A method of treating a subject about 65 years of age or older with R / R FL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21 - day dosing cycle, a second 21 - day dosing cycle, and a third 21 - day dosing cycle, (a) The first three - dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15 of the first dosing cycle respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose of mosunetuzumab (C2D1) administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle includes a single dose of mosunetuzumab (C3D1) administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, A method, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0360] Mosunetuzumab for use in the treatment of subjects about 65 years of age or older with R / R FL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose dosing cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, which are to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle includes a single dose of mosunetuzumab (C2D1) to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third dosing cycle includes a single dose of mosunetuzumab (C3D1) to be administered on day 1 of the third dosing cycle, where C3D1 is about 30 mg, Mosunetuzumab for use, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0361] Use of mosunetuzumab for the treatment of subjects about 65 years of age or older with R / R FL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of ofatumumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third administration cycle comprises a single dose (C3D1) of ofatumumab to be administered on day 1 of the third administration cycle, where C3D1 is about 30 mg, Use in a subject who has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0362] Use of ofatumumab in the manufacture of a medicament for use in the treatment of subjects about 65 years of age or older having R / R FL, wherein ofatumumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day administration cycle, a second 21-day administration cycle, and a third 21-day administration cycle, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of ofatumumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third administration cycle comprises a single dose (C3D1) of ofatumumab to be administered on day 1 of the third administration cycle, where C3D1 is about 30 mg, Use in a subject who has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0363] A method of treating a subject aged about 65 years or older having R / R FL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 8 dosing cycles of 21 days each, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The third to eighth dosing cycles each comprise a single dose (C3D1 - C8D1) of mosunetuzumab administered on day 1 of each dosing cycle, where each of C3D1 - C8D1 is about 30 mg, where the subject has relapsed after 2 or more prior lines of therapy or is refractory to 2 or more prior lines of therapy.

[0364] Mosunetuzumab for use in the treatment of a subject aged about 65 years or older having R / R FL, wherein mosunetuzumab is to be intravenously administered to the subject in a dosing regimen comprising 8 dosing cycles of 21 days each, (a) The first 3-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, where C2D1 is about 60 mg; and (c) The 3rd to 8th dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C8D1) to be administered on the first day of each dosing cycle, with each of C3D1 - C8D1 being approximately 30 mg, Mosunetuzumab for use, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0365] Use of mosunetuzumab for the treatment of subjects about 65 years of age or older with R / R FL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 8 twenty - one - day dosing cycles, (a) The first 3 - dose dosing cycle contains the first dose (C1D1), the second dose (C1D2), and the third dose (C1D3) of mosunetuzumab to be administered on the first, eighth, and fifteenth days of the first dosing cycle respectively, with C1D1 being approximately 1 mg, C1D2 being approximately 2 mg, and C1D3 being approximately 60 mg; (b) The second dosing cycle contains a single dose of mosunetuzumab (C2D1) to be administered on the first day of the second dosing cycle, with C2D1 being approximately 60 mg; and (c) The 3rd to 8th dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C8D1) to be administered on the first day of each dosing cycle, with each of C3D1 - C8D1 being approximately 30 mg, Use, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0366] Use of mosunetuzumab in the manufacture of a medicament for use in the treatment of subjects about 65 years of age or older with R / R FL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 8 twenty - one - day dosing cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to eighth administration cycles each include a single dose (C3D1 - C8D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C8D1 is about 30 mg, Use in a subject who has relapsed after two or more prior lines of therapy or who is refractory to two or more prior lines of therapy.

[0367] 151. A method of treating a subject about 65 years of age or older having R / R FL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty-one-day administration cycles, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg, The method, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0368] Mosunetuzumab for use in the treatment of subjects aged about 65 years or older with R / R FL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 cycles of 21-day dosing, (a) a first 3-dose dosing cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second dosing cycle comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) the third to seventeenth dosing cycles each comprising a single dose (C3D1 - C17D1) of mosunetuzumab to be administered on day 1 of each dosing cycle, wherein each of C3D1 - C17D1 is about 30 mg, Mosunetuzumab for use, wherein the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy.

[0369] Use of mosunetuzumab for the treatment of subjects aged about 65 years or older with R / R FL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 cycles of 21-day dosing, (a) a first 3-dose dosing cycle comprising a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab to be administered on days 1, 8, and 15 of the first dosing cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) a second dosing cycle comprising a single dose (C2D1) of mosunetuzumab to be administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The 3rd to 17th dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C17D1) to be administered on the first day of each dosing cycle, with each of C3D1 - C17D1 being approximately 30 mg, Use in a subject who has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

[0370] Use of mosunetuzumab in the manufacture of a medicament for use in treating a subject of about 65 years of age or older having R / R FL, wherein mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising 17 twenty - one - day dosing cycles, (a) The first 3 - dose dosing cycle contains the first dose (C1D1), the second dose (C1D2), and the third dose (C1D3) of mosunetuzumab to be administered on the first day, eighth day, and fifteenth day of the first dosing cycle respectively, with C1D1 being approximately 1 mg, C1D2 being approximately 2 mg, and C1D3 being approximately 60 mg; (b) The second dosing cycle contains a single dose of mosunetuzumab (C2D1) to be administered on the first day of the second dosing cycle, with C2D1 being approximately 60 mg; and (c) The 3rd to 17th dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C17D1) to be administered on the first day of each dosing cycle, with each of C3D1 - C17D1 being approximately 30 mg, Use in a subject who has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

[0371] 155. A method of treating a subject of about 65 years of age or older having R / R FL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first twenty - one - day dosing cycle, a second twenty - one - day dosing cycle, and a third twenty - one - day dosing cycle, (a) The first three-dose administration cycle includes mosunetuzumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third administration cycle includes a single dose (C3D1) of mosunetuzumab administered on day 1 of the third administration cycle, where C3D1 is about 30 mg, The subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines, and the dosing regimen further (i) administering a corticosteroid, where a single dose of corticosteroid is administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; (ii) administering an antihistamine, where a single dose of antihistamine is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab; and / or (iii) administering an antipyretic, where a single dose of antipyretic is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of mosunetuzumab, a method comprising.

[0372] Mosunetuzumab for use in the treatment of subjects about 65 years of age or older with R / R FL, where mosunetuzumab is to be administered intravenously to the subject in a dosing regimen comprising at least a first 21-day administration cycle, a second 21-day administration cycle, and a third 21-day administration cycle, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) to be administered on days 1, 8, an...

Claims

1. A method of treating a subject about 65 years of age or older having relapsed or refractory (R / R) non-Hodgkin lymphoma (NHL), comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first dosing cycle, a second dosing cycle, and a third dosing cycle, (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab, wherein said C1D1 is about 1 mg, said C1D2 is about 2 mg, and said C1D3 is about 60 mg; (b) said second dosing cycle comprises a single dose (C2D1) of mosunetuzumab, wherein said C2D1 is about 60 mg; and (c) said third dosing cycle comprises a single dose (C3D1) of mosunetuzumab, wherein said C3D1 is about 30 mg.

2. The method of claim 1, wherein the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

3. The method of claim 2, wherein the two or more prior treatment lines comprise an anti-CD20 monoclonal antibody, an alkylating agent, or both an anti-CD20 monoclonal antibody and an alkylating agent.

4. The method according to any one of claims 1 to 3, wherein the R / R NHL is R / R follicular lymphoma (FL), R / R transformed FL (trFL), or R / R diffuse large B-cell lymphoma (DLBCL).

5. The method of claim 4, wherein the R / R NHL is R / R FL.

6. The method of claim 5, wherein the R / R FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375-90), but not 3b.

7. The method according to any one of claims 1 to 6, wherein the first administration cycle, the second administration cycle, and the third administration cycle are each 21-day administration cycles.

8. The method according to any one of claims 1 to 7, comprising administering the C1D1, the C1D2, and the C1D3 on the 1st day, the 8th day, and the 15th day, respectively, of the first administration cycle.

9. The method according to any one of claims 1 to 8, comprising administering the C2D1 on the 1st day of the second administration cycle.

10. The method according to any one of claims 1 to 9, comprising administering the C3D1 on the 1st day of the third administration cycle.

11. The method according to any one of claims 1 to 10, wherein the dosing regimen further comprises one or more additional administration cycles.

12. The method according to claim 11, wherein the dosing regimen comprises 5 to 14 additional administration cycles.

13. The method according to claim 12, wherein the dosing regimen comprises 5 additional administration cycles.

14. The method according to claim 12, wherein the dosing regimen comprises 14 additional administration cycles.

15. The method according to any one of claims 11 to 14, wherein each of the one or more additional administration cycles is a 21-day administration cycle.

16. The method according to any one of claims 11 to 15, wherein each of the one or more additional administration cycles comprises an additional single dose of mosunetuzumab.

17. The method according to claim 16, wherein the additional single dose of mosunetuzumab is administered to the subject on the 1st day of each additional administration cycle.

18. The method according to claim 16 or 17, wherein the additional single dose of mosunetuzumab is about 30 mg.

19. The method according to any one of claims 1 to 18, wherein mosunetuzumab is administered by intravenous infusion.

20. A method of treating a population of subjects about 65 years of age or older with R / R NHL, comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, wherein C3D1 is about 30 mg.

21. A method of treating a population of subjects about 65 years of age or older with R / R NHL, comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising eight 21-day dosing cycles, (a) The first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) the second dosing cycle comprises a single dose of mosunetuzumab (C2D1) administered on day 1 of the second dosing cycle, said C2D1 being about 60 mg; and (c) the third to eighth dosing cycles each comprise a single dose of mosunetuzumab (C3D1-C8D1) administered on day 1 of each dosing cycle, each of said C3D1-C8D1 being about 30 mg, a method.

22. A method of treating a population of subjects about 65 years of age or older with R / R NHL, comprising intravenously administering mosunetuzumab to each subject in a dosing regimen comprising 17 twenty-one day dosing cycles, (a) the first three-dose dosing cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15 of the first dosing cycle, respectively, said C1D1 being about 1 mg, said C1D2 being about 2 mg, and said C1D3 being about 60 mg; (b) the second dosing cycle comprises a single dose of mosunetuzumab (C2D1) administered on day 1 of the second dosing cycle, said C2D1 being about 60 mg; and (c) the third to seventeenth dosing cycles each comprise a single dose of mosunetuzumab (C3D1-C17D1) administered on day 1 of each dosing cycle, each of said C3D1-C17D1 being about 30 mg, a method.

23. The method according to any one of claims 20-22, wherein each subject in the population of subjects has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

24. The method according to claim 23, wherein the two or more prior treatment lines comprise an anti-CD20 monoclonal antibody, an alkylating agent, or both an anti-CD20 monoclonal antibody and an alkylating agent.

25. The method according to any one of claims 20-24, wherein the R / R NHL is R / R FL, R / R trFL or R / R DLBCL.

26. The method according to claim 25, wherein the R / R NHL is R / R FL.

27. The method according to claim 26, wherein the R / R FL is histologically demonstrated to be grade 1, 2 or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375 - 90), but not 3b.

28. The method according to any one of claims 20 - 27, wherein mosunetuzumab is administered by intravenous infusion.

29. The method according to any one of claims 20 - 27, wherein the objective response rate in the population of subjects is 65% or more.

30. The method according to claim 29, wherein the objective response rate in the population of subjects is 75% or more.

31. The method according to claim 30, wherein the objective response rate in the population of subjects is 85% or more.

32. The method according to any one of claims 20 - 27, wherein the complete response rate in the population of subjects is 50% or more.

33. The method according to claim 32, wherein the complete response rate in the population of subjects is 60% or more.

34. The method according to claim 33, wherein the complete response rate in the population of subjects is 70% or more.

35. The method according to any one of claims 20 - 27, wherein 40% or more of the subjects with an objective response maintain remission for 18 months.

36. The method according to claim 35, wherein 50% or more of the subjects with an objective response maintain remission for 18 months.

37. The method according to any one of claims 20 to 27, wherein 50% or more of the subjects having a complete response maintain a complete remission for 18 months.

38. The method according to claim 37, wherein 60% or more of the subjects having a complete response maintain a complete remission for 18 months.

39. The method according to any one of claims 20 to 27, wherein the median duration of response in the population of the subjects is 9 months or more.

40. The method according to claim 39, wherein the median duration of response in the population of the subjects is 15 months or more.

41. The method according to any one of claims 20 to 27, wherein the median duration of complete response in the population of the subjects is 12 months or more.

42. The method according to claim 41, wherein the median duration of complete response in the population of the subjects is 16 months or more.

43. The method according to any one of claims 20 to 27, wherein 35% or more of the subjects have progression-free survival of 18 months.

44. The method according to claim 43, wherein 45% or more of the subjects have progression-free survival of 18 months.

45. The method according to any one of claims 20 to 27, wherein the median progression-free survival in the population of the subjects is 12 months or more.

46. The method according to claim 45, wherein the median progression-free survival in the population of the subjects is 17 months or more.

47. The method according to any one of claims 20 to 27, wherein the proportion of serious adverse events excluding grade 5 malignant neoplasm progression in the population of the subjects is 45% or less.

48. The method according to claim 47, wherein the proportion of serious adverse events excluding grade 5 malignant neoplasm progression in the population of the subjects is 40% or less.

49. The method according to any one of claims 20 to 27, wherein the percentage of serious adverse events related to mosunetuzumab in the population of interest is 40% or less.

50. The method according to claim 49, wherein the percentage of serious adverse events related to mosunetuzumab in the population of interest is 30% or less.

51. The method according to any one of claims 20 to 27, wherein the percentage of cytokine release syndrome of grade 3 or higher (defined by the American Society for Transplantation and Cellular Therapy, 2018; ASTCT) in the population of interest is 5% or less.

52. The method according to claim 51, wherein the percentage of cytokine release syndrome having a grade of 3 or higher (defined by the ASTCT) in the population of interest is 3% or less.

53. The method according to any one of claims 20 to 27, wherein the percentage of cytokine release syndrome of any grade (defined by the ASTCT) in the population of interest is 40% or less.

54. The method according to claim 53, wherein the percentage of cytokine release syndrome of any grade (defined by the ASTCT) in the population of interest is 30% or less.

55. A method of achieving objective response, complete response or progression-free survival in a subject of about 65 years of age or older with R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) administered on day 1, day 8, and day 15 of the first administration cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of ofatumumab administered on day 1 of the second administration cycle, wherein C2D1 is about 60 mg; and (c) The third administration cycle comprises a single dose (C3D1) of ofatumumab administered on day 1 of the third administration cycle, wherein C3D1 is about 30 mg, a method.

56. A method of achieving objective response, complete response or progression-free survival in a subject about 65 years of age or older having R / R NHL, comprising intravenously administering ofatumumab to the subject in a dosing regimen comprising 8 cycles of 21-day administrations, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) administered on day 1, day 8, and day 15 of the first administration cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of ofatumumab administered on day 1 of the second administration cycle, wherein C2D1 is about 60 mg; and (c) The third to eighth administration cycles each comprise a single dose (C3D1 - C8D1) of ofatumumab administered on day 1 of each administration cycle, wherein each of C3D1 - C8D1 is about 30 mg, a method.

57. A method of achieving objective response, complete response or progression-free survival in a subject about 65 years of age or older having R / R NHL, comprising intravenously administering ofatumumab to the subject in a dosing regimen comprising 17 cycles of 21-day administrations, (a) The first three-dose administration cycle includes a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle includes a single dose (C2D1) of mosunetuzumab administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each include a single dose (C3D1 - C17D1) of mosunetuzumab administered on day 1 of each administration cycle, where each of C3D1 - C17D1 is about 30 mg.

58. The method according to any one of claims 55 - 57, wherein the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines.

59. The method according to claim 58, wherein the two or more prior treatment lines include an anti - CD20 monoclonal antibody, an alkylating agent, or both an anti - CD20 monoclonal antibody and an alkylating agent.

60. The method according to any one of claims 55 - 59, wherein the R / R NHL is R / R FL, R / R trFL, or R / R DLBCL.

61. The method according to claim 60, wherein the R / R NHL is R / R FL.

62. The method according to claim 61, wherein the R / R FL is histologically demonstrated to be grade 1, 2, or 3a according to the World Health Organization classification of lymphoid neoplasms (as referenced in Swerdlow SH, et al. Blood 2016;127:2375 - 90), but not 3b.

63. The method according to any one of claims 55 - 62, wherein mosunetuzumab is administered by intravenous infusion.

64. The method according to any one of claims 55 to 63, wherein the subject achieves an objective therapeutic effect.

65. The method according to any one of claims 55 to 63, wherein the subject achieves a complete therapeutic effect.

66. The method according to any one of claims 55 to 63, wherein the progression-free survival is maintained for 12 months or more.

67. The method according to claim 66, wherein the progression-free survival is maintained for 18 months or more.

68. The method according to any one of claims 1 to 67, further comprising administering one or more additional therapeutic agents to the subject or each subject in the population of subjects.

69. The method according to claim 68, wherein the one or more additional therapeutic agents include tocilizumab.

70. The method according to claim 68 or 69, wherein the one or more additional therapeutic agents include corticosteroids.

71. The method according to claim 70, wherein the corticosteroid includes dexamethasone or methylprednisolone.

72. The method according to claim 70 or 71, wherein the corticosteroid is administered to the subject or each subject in the population of subjects at least 1 hour before administration of any dose of mosunetuzumab.

73. The method according to any one of claims 70 to 72, wherein the corticosteroid is administered only during administration cycle 1 or administration cycle 2.

74. The method according to any one of claims 70 to 73, wherein the corticosteroid is administered intravenously.

75. The method according to any one of claims 70 to 74, wherein the corticosteroid includes dexamethasone and is administered at a dose of about 20 mg. Claim 76 The method according to any one of claims 70 to 74, wherein the corticosteroid comprises methylprednisolone and is administered at a dose of about 80 mg. Claim 77 The method according to any one of claims 68 to 76, wherein the one or more additional therapeutic agents comprise an antihistamine. Claim 78 The method according to claim 77, wherein the antihistamine is administered to the subject or each subject in the population of subjects at least 30 minutes prior to the administration of any dose of mosunetuzumab. Claim 79 The method according to claim 77 or 78, wherein the antihistamine is administered only during administration cycle 1 or administration cycle 2. Claim 80 The method according to any one of claims 77 to 79, wherein the antihistamine is administered orally or intravenously. Claim 81 The method according to any one of claims 77 to 80, wherein the antihistamine comprises diphenhydramine hydrochloride and is administered at a dose of about 50 to 100 mg. Claim 82 The method according to any one of claims 68 to 81, wherein the one or more additional therapeutic agents comprise an antipyretic. Claim 83 The method according to claim 82, wherein the antipyretic is administered to the subject or each subject in the population of subjects at least 30 minutes prior to the administration of any dose of mosunetuzumab. Claim 84 The method according to claim 82 or 83, wherein the antipyretic is administered only during administration cycle 1 or administration cycle 2. Claim 85 The method according to any one of claims 82 to 84, wherein the antipyretic is administered orally. Claim 86 The method according to any one of claims 82 to 85, wherein the antipyretic agent contains acetaminophen and is administered at a dose of about 500 to 1000 mg. **Claim 87** A method of treating a subject about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first 21-day dosing cycle, a second 21-day dosing cycle, and a third 21-day dosing cycle, (a) The first three-dose administration cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third dosing cycle comprises a single dose (C3D1) of mosunetuzumab administered on day 1 of the third dosing cycle, wherein C3D1 is about 30 mg, wherein the subject has relapsed after two or more prior treatment lines or is refractory to two or more prior treatment lines. **Claim 88** A method of treating a subject about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising eight 21-day dosing cycles, (a) The first three-dose administration cycle comprises a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15, respectively, of the first dosing cycle, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle comprises a single dose (C2D1) of mosunetuzumab administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third to eighth dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C8D1) administered on day 1 of each dosing cycle, and each of C3D1 - C8D1 is about 30 mg, wherein the subject has relapsed after two or more prior lines of treatment or is refractory to two or more prior lines of treatment.

89. A method of treating a subject about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising 17 twenty - one - day dosing cycles, (a) The first three - dose dosing cycle contains a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) of mosunetuzumab administered on days 1, 8, and 15 of the first dosing cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second dosing cycle contains a single dose of mosunetuzumab (C2D1) administered on day 1 of the second dosing cycle, wherein C2D1 is about 60 mg; and (c) The third to seventeenth dosing cycles each contain a single dose of mosunetuzumab (C3D1 - C17D1) administered on day 1 of each dosing cycle, and each of C3D1 - C17D1 is about 30 mg, wherein the subject has relapsed after two or more prior lines of treatment or is refractory to two or more prior lines of treatment.

90. A method of treating a subject about 65 years of age or older having R / R NHL, comprising intravenously administering mosunetuzumab to the subject in a dosing regimen comprising at least a first twenty - one - day dosing cycle, a second twenty - one - day dosing cycle, and a third twenty - one - day dosing cycle, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) administered on days 1, 8, and 15 of the first administration cycle, respectively, where C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of ofatumumab administered on day 1 of the second administration cycle, where C2D1 is about 60 mg; and (c) The third administration cycle comprises a single dose (C3D1) of ofatumumab administered on day 1 of the third administration cycle, where C3D1 is about 30 mg, where the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) administering a corticosteroid, where a single dose of the corticosteroid is administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab; (ii) administering an antihistamine, where a single dose of the antihistamine is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab; and / or (iii) administering an antipyretic, where a single dose of the antipyretic is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab, a method.

91. A method of treating a subject of about 65 years of age or older having R / R NHL, comprising intravenously administering ofatumumab to the subject in a dosing regimen comprising 8 twenty-one-day administration cycles, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3), which are administered on days 1, 8, and 15 of the first administration cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of ofatumumab administered on day 1 of the second administration cycle, wherein C2D1 is about 60 mg; and (c) The third to eighth administration cycles each comprise a single dose (C3D1 - C8D1) of ofatumumab administered on day 1 of each administration cycle, wherein each of C3D1 - C8D1 is about 30 mg, the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab, a method.

92. A method of treating a subject about 65 years of age or older having R / R NHL, comprising intravenously administering ofatumumab to the subject in a dosing regimen comprising 17 twenty-one day administration cycles, (a) The first three-dose administration cycle comprises ofatumumab at a first dose (C1D1), a second dose (C1D2), and a third dose (C1D3) administered on days 1, 8, and 15 of the first administration cycle, respectively, wherein C1D1 is about 1 mg, C1D2 is about 2 mg, and C1D3 is about 60 mg; (b) The second administration cycle comprises a single dose (C2D1) of ofatumumab administered on day 1 of the second administration cycle, wherein C2D1 is about 60 mg; and (c) The third to seventeenth administration cycles each comprise a single dose (C3D1 - C17D1) of ofatumumab administered on day 1 of each administration cycle, wherein each of C3D1 - C17D1 is about 30 mg, where the subject has relapsed after two or more prior lines of therapy or is refractory to two or more prior lines of therapy, and the dosing regimen further comprises (i) administering a corticosteroid, wherein a single dose of the corticosteroid is administered to the subject at least 1 hour prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab; (ii) administering an antihistamine, wherein a single dose of the antihistamine is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab; and / or (iii) administering an antipyretic, wherein a single dose of the antipyretic is administered to the subject at least 30 minutes prior to each of the administrations of C1D1, C1D2, C1D3, and C2D1 of ofatumumab, a method.

93. The method according to any one of claims 87 - 92, wherein the two or more prior lines of therapy comprise an anti-CD20 monoclonal antibody, an alkylating agent, or both an anti-CD20 monoclonal antibody and an alkylating agent.

94. The method according to any one of claims 87 to 93, wherein the R / R NHL is R / R FL, R / R trFL or R / R DLBCL.

95. The method according to claim 94, wherein the R / R NHL is R / R FL.

96. The method according to claim 95, wherein the R / R FL is histologically demonstrated to be grade 1, 2 or 3a according to the World Health Organization classification of lymphoid neoplasms (as referred to in Swerdlow SH, et al. Blood 2016; 127: 2375-90), but not 3b.

97. The method according to any one of claims 87 to 96, wherein mosunetuzumab is administered by intravenous infusion.

98. The method according to any one of claims 90 to 97, wherein (i) a single dose of the corticosteroid is administered prior to the administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle; (ii) a single dose of the antihistamine is administered prior to the administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle; and / or (iii) a single dose of the antipyretic is administered prior to the administration of any dose of mosunetuzumab in any one of one or more dosing cycles after the second dosing cycle.

99. The method according to any one of claims 90 to 98, wherein (i) the corticosteroid is administered intravenously; (ii) the antihistamine is administered orally or intravenously; and / or (iii) the antipyretic is administered orally.

100. The method according to any one of claims 90 to 99, wherein (i) the corticosteroid comprises dexamethasone and is administered at a dose of about 20 mg, or the corticosteroid comprises methylprednisolone and is administered at a dose of about 80 mg; (ii) the antihistamine comprises diphenhydramine hydrochloride and is administered at a dose of about 50 - 100 mg; and / or (iii) the antipyretic comprises acetaminophen and is administered at a dose of about 500 - 1000 mg, a method.

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