Methods for treating prostate cancer

Abstract

The present disclosure relates to the treatment of (a) biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer with an anti-STEAP1 antigen binding protein.

Description

32512 / 70538METHODS FOR TREATING PROSTATE CANCERFIELD OF THE INVENTION

[0001] The present disclosure relates to the field of oncology. In particular, the disclosure relates to the treatment of (a) biochemical recurrence of nonmetastatic castrationsensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer with an anti-STEAP1 antigen binding protein.INCORPORATION BY REFERENCE

[0002] This application incorporates by reference International Patent Publication No. WO 2020 / 010079, filed on July 2, 2019; and International Publication No. WO 2019 / 157340, filed 2 / 8 / 2019, both of which are expressly incorporated herein by reference in their entirety, with particular reference to the figures, legends and claims therein.INCORPORATION BY REFERENCE OF THE SEQUENCE LISTING

[0003] This application contains, as a separate part of disclosure, a Sequence Listing in computer-readable form (Filename: 70538_SeqListing.xml; Size: 30,731 bytes; Created: August 7, 2025) which is incorporated by reference herein in its entirety.BACKGROUND OF THE INVENTION

[0004] Prostate cancer is one of the most frequently diagnosed noncutaneous cancer and one of the leading causes of cancer deaths in men in the United States (U.S.). In the U.S., an estimated 313,780 new cases of prostate cancer (30% of all new cancer cases in men) and 35,770 prostate cancer related deaths (11% of cancer deaths in men) are expected in 2025 (Siegel et al., Cancer statistics, 2025. CA Cancer J Clin. 2025; 75(1 ): IQ- 45).

[0005] Survival rates vary among men with prostate cancer but are strongly related to disease stage and location of disease (i.e., local vs metastatic). While the 5-year survival rate for men with localized prostate cancer in the US is nearly 100%, the 5-year survival rate drops to as low as 31% for men with metastatic disease (Cancer.Net, 2020). In 2015, there were an estimated 365 000 new cases and 77 000 deaths from prostate cancer in the European Union (10% of total cancer deaths) (EU Science Hub, 2018). In China, there were an estimated 78,300 new cases of prostate cancer, with 33,600 deaths in 2016. During 2000-2016, there was an increasing trend of incidence rate for prostate cancer. The average annual percentage changed was 7.1% (Zheng et al, 2022).32512 / 70538

[0006] Treatment for patients diagnosed with metastatic prostate cancer has included continuous and intermittent androgen-deprivation therapy (ADT). Docetaxel and the androgen receptor pathway inhibitors (ARPI), abiraterone, enzalutamide, apalutamide, and darolutamide, are approved therapies. Current standard of care (SOC) for patients with metastatic hormone sensitive prostate cancer (mHSPC) patients includes doublet therapy which combines an androgen deprivation therapy (ADT) with androgen receptor pathway inhibitors (ARPI) abiraterone acetate, enzalutamide, apalutamide and darolutamide (Chi et al, 2021 ; Conduit et al, 2025; Davis et al, 2019; Parker et al, 2018, Saad et al, 2024) with or without docetaxel (PEACE-1 , ARASENS) as third agent (Fizazi et al, 2022; Smith et al, 2022). There are no trials directly comparing the efficacy of a doublet (ARPI+ADT) versus a triplet regimen (ARPI + ADT + docetaxel) and both are considered appropriate options for patients with mHSPC (Fizazi et al, 2019; Fizazi et al, 2023). A consistent improvement in radiographic progression-free survival, prostate-specific antigen (PSA) responses and overall survival has been observed in when ARPI is included in the treatment of mHSPC. Thus, treatment selection is tailored by considering patient’s quality of life, comorbidities, and accessibility of drug regimen as well as prognostic factors such as the presence of metastatic disease at diagnosis and volume of metastatic disease. Metastatic prostate cancer often develops resistance to ADT (also known as “castration resistance”) due to increased intratumoral steroidogenesis, altered steroid-transporter expression, increased androgen receptor expression (e.g., androgen receptor amplification), and other mechanisms (Galletti et al, Cancer Treat Rev. 2017;57:16-27).

[0007] Since 2010, five new therapeutic agents for metastatic castration resistant prostate cancer (mCRPC) have been approved based on survival benefit: cabazitaxel (Jevtana®), sipuleucel-T (Provenge®), abiraterone (Zytiga®), enzalutamide (Xtandi®), and radium-223 (Xofigo®). However, the optimal sequence or combination of available therapies in mCRPC is largely unknown. Food and Drug Administration (FDA) has also recently approved the following therapies for specific subgroups of patients with mCRPC: poly ADP ribose polymerase (PARP) inhibitors, olaparib (Lynparza®), rucaparib (Rubraca®); the programmed cell death protein 1 (PD-1) inhibitor, pembrolizumab (Keytruda®); and a radioligand therapeutic targeting prostate-specific membrane antigen, lutetium Lu 177 vipivotide tetraxetan (PLUVICTO®).

[0008] There is a need for treatment options for patients who have early prostate cancer disease.

[0009] Six-transmembrane epithelial antigen of the prostate 1 (STEAP1 ), a surface antigen containing 3 short extra-cellular loop regions, is overexpressed in prostate cancer32512 / 70538(Hubert et al, Proc Natl Acad Sci USA. 1999;96(25):14523-8) and Ewing sarcoma (Grunewald et al, Mol Cancer Res. 2012 Jan;10(1 ):52-65), and its expression correlates with prostate cancer disease stage (Gomes et al, Urol Oncol. 2014 Jan;32(1 ):53.e23-9). Xaluritamig is a novel XmAb® 2 + 1 bispecific antibody designed to direct T effector cells (through CD3 binding) to prostate cancer cells expressing STEAP1 . In nonclinical studies, xaluritamig demonstrated potent cytotoxicity in prostate cancer cell lines and tumor regression in a preclinical xenograft model. In a nonclinical toxicology study in cynomolgus monkey, tolerated doses of xaluritamig were identified, with some dosing regimens including a lower day 1 dose (step dose) to reduce the risk of acute cytokine-related toxicities associated with T cell activation.SUMMARY OF THE INVENTION

[0010] The present disclosure provides a method of treating a patient having prostate cancer. The prostate cancer is (a) biochemical recurrent prostate cancer (“BCR”) ), (b) localized prostate cancer, or (c) metastatic prostate cancer. The method comprises administering to the patient a pharmaceutical composition comprising an anti-STEAP1 antigen binding protein at a dose of about 0.1 mg to about 2.0 mg. The anti-STEAP1 antigen binding protein comprises (i) a STEAP1 antigen binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 1 1 ; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14; and (ii) a CD3 binding domain that comprises a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6. In an embodiment, the prostate cancer is high-risk BCR. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormonesensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0011] The present disclosure also provides use of an anti-STEAP1 antigen binding protein for preparation of a medicament for treating prostate cancer, wherein the medicament is formulated for administration at a dose of about 0.1 mg to about 2.0 mg. The present disclosure also provides use of an anti-STEAP1 antigen binding protein in the32512 / 70538 manufacture of a medicament for treating prostate cancer, wherein the medicament is formulated for administration at a dose of about 0.1 mg to about 2.0 mg. The present disclosure also provides an anti-STEAP1 antigen binding protein for use in the treatment of prostate cancer, wherein the anti-STEAP1 antigen binding protein is formulated for administration at a dose of about 0.1 mg to about 2.0 mg. The prostate cancer is (a) high- risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer. The anti- STEAP1 antigen binding protein comprises (i) a STEAP1 antigen binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14; and (ii) a CD3 binding domain that comprises a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0012] The present disclosure also provides use of an anti-STEAP1 antigen binding protein in the manufacture of a medicament for treating prostate cancer, wherein the medicament is formulated for administration at a dose of about 0.1 mg to about 2.0 mg. The present disclosure also provides use of an anti-STEAP1 antigen binding protein in the manufacture of a medicament for treating prostate cancer, wherein the medicament is formulated for administration at a dose of about 0.1 mg to about 2.0 mg. The present disclosure also provides an anti-STEAP1 antigen binding protein for use in the treatment of prostate cancer, wherein the anti-STEAP1 antigen binding protein is formulated for administration at a dose of about 0.1 mg to about 2.0 mg. The prostate cancer is (a) high- risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic32512 / 70538 hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. The anti-STEAP1 antigen binding protein comprises (i) a STEAP1 antigen binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14; and (ii) a CD3 binding domain that comprises a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0013] In an embodiment, the dose of anti-STEAP1 antigen binding protein is about 0.1 mg to about 1 .5 mg, about 0.1 mg to about 2 mg, or about 0.75 mg to about 1 .5 mg. In an embodiment, the dose is 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.75, 0.8 mg, 0.9 mg, 1 .0 mg, 1.1 mg, 1 .2 mg, 1 .3 mg, 1 .4 mg, 1 .5 mg, 1 .6 mg, 1 .7 mg, 1 .8 mg, or 1 .9 mg. In an embodiment, the dose is about 0.1 mg. In an embodiment, the dose is about 0.3 mg. In an embodiment, the dose is about 0.75 mg. In an embodiment, the dose is about 1 .0 mg. In an embodiment, the dose is about 1 .5 mg. In an embodiment, the dose is 0.1 mg. In an embodiment, the dose is 0.3 mg. In an embodiment, the dose is 0.75 mg. In an embodiment, the dose is 1 .0 mg. In an embodiment, the dose is 1 .5 mg. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume32512 / 70538 metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0014] In an embodiment, the dose is administered once per one week. In an embodiment, the dose is administered once per two weeks. In an embodiment, the dose is administered once per three weeks. In an embodiment, the dose is administered once per four weeks. In an embodiment, the dose is administered by intravenous administration. In an embodiment, the dose is administered once per week beginning in cycle 1 . In an embodiment, the dose is administered once per week beginning in cycle 2. In an embodiment, the dose is administered once per two weeks beginning in cycle 2. In an embodiment, the dose is administered once per three weeks beginning in cycle 2. In an embodiment, the dose is administered once per four weeks beginning in cycle 2. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per two weeks beginning on day one of cycle 2. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per two weeks once the target dose has been achieved. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per three weeks once the target dose has been achieved. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per four weeks once the target dose has been achieved. In an embodiment, the dose is administered once per week for the first cycle, then administered once per two weeks in cycle 2, and then administered once per three weeks in cycles 3 and beyond. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0015] In an embodiment, six cycles of administrations are provided to the patient. For instance, a dose of anti-STEAP1 antigen binding protein (e.g., any of the doses described above) is administered once per week for the first cycle, and then a dose of anti-32512 / 70538STEAP1 antigen binding protein is administered once per two weeks once for cycles 2 through 6. Alternatively, after the first cycle is completed, a dose of anti-STEAP1 antigen binding protein is administered once every two weeks for cycles 2 through 11 (or cycles 2 through 12), resulting in a total of 12 cycles of administrations. Alternatively, after the first cycle is completed, a dose of anti-STEAP1 antigen binding protein is administered once every two weeks for cycles 2 through 23, resulting in a total of 24 cycles of administrations. Alternatively, after the first cycle is completed, a dose of anti-STEAP1 antigen binding protein is administered once every two weeks for cycle 2 and once every 4 weeks for cycles 3 through 12, resulting in a total of 12 cycles of administration. In an embodiment, high-risk BCR patients are administered a dose of anti-STEAP1 antigen binding protein once every four weeks beginning in cycle 3, and each cycle includes two doses of anti-STEAP1 antigen binding protein. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0016] In an embodiment, the anti-STEAP1 antigen binding protein is administered by step dosing, wherein multiple doses are administered in increasing amounts. In this regard, the anti-STEAP1 antigen binding protein may be administered such that the dose administered is increased in two steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen binding protein is administered such that the dose is increased in three steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen binding protein is administered on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0.3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.5 mg, day 13, 14, or 15 at a dose in the range of about 0.8 mg to about 1 .2 mg, and day 20, 21 , or 22 at a dose in the range of about 1 .2 mg to about 1 .6 mg (a representative “step dosing cycle”). In an embodiment, the method further comprises administering to the patient a dose of an anti- STEAP1 antigen binding protein once per week, once per two weeks, once per three weeks, or once per four weeks after administration of the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 mg after the step dosing cycle. In32512 / 70538 an embodiment, the anti-STEAP1 antigen binding protein is administered at 1.0 mg once every two weeks after the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 .5 mg after the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 .5 mg once every two weeks after the step dosing cycle. Alternatively, in an embodiment, the anti-STEAP1 antigen binding protein is administered such that the dose is increased in two steps. In an embodiment, the anti-STEAP1 antigen binding protein is administered on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0.3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.5 mg, day 13, 14, or 15 at a dose in the range of about 0.8 mg to about 1 .2 mg. In an embodiment, the method further comprises administering to the patient a dose of anti- STEAP1 antigen binding protein once per week, once per two weeks, once per three weeks, or once per four weeks after administration of the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 .0 mg after the step dosing cycle. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormonesensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0017] In an embodiment, the anti-STEAP1 antigen binding protein is administered in three doses in cycle 1. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 .0 mg after cycle 1 . In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.32512 / 70538

[0018] In an embodiment, the anti-STEAP1 antigen binding protein is administered by step dosing, wherein multiple doses are administered in increasing amounts. In this regard, the anti-STEAP1 antigen binding protein may be administered such that the dose administered is increased in two steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen binding protein is administered such that the dose is increased in three steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen binding protein is administered on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0.3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.5 mg, day 13, 14, or 15 at a dose in the range of about 0.8 mg to about 1 .2 mg, and day 20, 21 , or 22 at a dose in the range of about 1 .2 mg to about 1 .6 mg. In an embodiment, the anti-STEAP1 antigen binding protein is administered on day 1 at 0.1 mg, day 8 at 0.3 mg, day 15 at 1 .0 mg, and day 22 at 1 .5 mg (a representative “step dosing cycle”). In an embodiment, the method further comprises administering to the patient a dose of an anti-STEAP1 antigen binding protein once per week, once per two weeks, once per three weeks, or once per four weeks after administration of the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 .5 mg once every two weeks after the step dosing cycle. Alternatively, in an embodiment, the anti-STEAP1 antigen binding protein is administered on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0.3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.5 mg, day 13, 14, or 15 at a dose in the range of about 0.8 mg to about 1 .2 mg. In an embodiment, the anti-STEAP1 antigen binding protein is administered on day 1 at 0.1 mg, day 8 at 0.3 mg, day 15 at 1.0 mg, (a representative “step dosing cycle”). In an embodiment, the method further comprises administering to the patient a dose of an anti-STEAP1 antigen binding protein once per week, once per two weeks, or once per four weeks after administration of the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1.0 mg once every two weeks or once every four weeks after completing the step dosing cycle. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormonesensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.32512 / 70538

[0019] In an embodiment, the anti-STEAP1 antigen binding protein is administered in two cycles, in an embodiment, the first cycle comprises administering the anti-STEAP1 antigen binding protein on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0.3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.5 mg, day 13, 14, or 15 at a dose in the range of about 0.8 mg to about 1 .2 mg. In an embodiment, the first cycle comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1 .0 mg. The second cycle comprises administering the anti- STEAP1 antigen binding protein at 1 .0 mg once every two weeks after cycle 1 is completed. In various aspects, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1 .0 mg once every two weeks for 3 months after cycle 1 is completed. In various aspects, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1.0 mg once every two weeks for five months after cycle 1 is completed. In an embodiment, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1.0 mg once every two weeks for 11 months after cycle 1 is completed. In an embodiment, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1 .0 mg once every two weeks for 23 months after cycle 1 is completed. In an embodiment, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1 .0 mg once every two weeks for 11 months after cycle 1 is completed. In an embodiment, cycle 2 comprises administering the anti- STEAP1 antigen binding protein at 1 .0 mg once every two weeks for 23 months after cycle 1 is completed. Optionally, the cycles are 28 days in length. Optionally, the cycles are 56 days in length if the doses are given every 4 weeks to capture 2 doses per cycle. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormonesensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0020] In an embodiment, the anti-STEAP1 antigen binding protein is administered in two cycles. In an embodiment, the first cycle comprises administering the anti-STEAP1 antigen binding protein on day 1 or day 2 at 0.1 mg to about 0.3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.5 mg, day 13, 14, or 15 at a dose in the range of about 0.8 mg to about 1 .2 mg, and day 20, 21 , or 22 at a dose in the range of about 1 .2 mg32512 / 70538 to about 1 .6 mg In an embodiment, the first cycle comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, day 15 at 1 .0 mg, and day 22 at 1 .5 mg. The second cycle comprises administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks after cycle 1 is completed. In various aspects, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1.5 mg once every two weeks for 3 months after cycle 1 is completed. In various aspects, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks for five months after cycle 1 is completed. In an embodiment, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks for 11 months after cycle 1 is completed. In an embodiment, cycle 2 comprises administering the anti- STEAP1 antigen binding protein at 1 .5 mg once every two weeks for 23 months after cycle 1 is completed. Optionally, the cycles are 28 days in length. Optionally, the cycles are 56 days in length if the doses are given every 4 weeks to capture 2 doses per cycle. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormonesensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0021] In an embodiment, the anti-STEAP1 antigen binding protein is administered in six cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0. 3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.4 mg, day 14, 15, or 16 at a dose in the range of about 0.8 mg to about 1 .2 mg, and day 21 , 22, or 23 at a dose in the range of about 1 .3 mg to about 1.6 mg. Cycles 2-6 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .5 mg once every two weeks. Alternatively, cycles 2-6 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .0 mg once every two weeks. In embodiment, the six cycles are repeated as a maintenance therapy (i.e., in the absence of progression or biochemical recurrence). In an embodiment, the six cycles are repeated until an optimal PSA nadir (e.g., < 2 ng / mL) has been achieved. In an embodiment, the patient has a biochemical recurrence and the anti-STEAP1 antigen binding protein is administered for an additional six cycles. Alternatively, maintenance therapy may start with32512 / 70538 the target dose every two weeks, every three weeks, or every four weeks without stepdosing. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0022] In another aspect, the anti-STEAP1 antigen binding protein is administered in 12 cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0. 3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.4 mg, day 14, 15, or 16 at a dose in the range of about 0.8 mg to about 1 .2 mg, and day 21 , 22, or 23 at a dose in the range of about 1 .3 mg to about 1.6 mg. Cycles 2-12 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .5 mg once every two weeks. Alternatively, the target dose is 1 .0. mg, and cycles 2-12 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .0 mg once every two weeks. Each cycle is optionally 28 days. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0023] In another aspect, the anti-STEAP1 antigen binding protein is administered in 18 cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0. 3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.4 mg, day 14, 15, or 16 at a dose in the range of about 0.8 mg to about 1 .2 mg, and day 21 , 22, or 23 at a dose in the range of about 1 .3 mg to about 1.6 mg. Cycles 2-18 each comprise administering the anti-STEAP1 antigen binding32512 / 70538 protein at about 1 .5 mg once every two weeks. Alternatively, the target dose is 1 .0. mg, and cycles 2-18 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .0 mg once every two weeks. Each cycle is optionally 28 days. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0024] In another aspect, the anti-STEAP1 antigen binding protein is administered in 24 cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 or day 2 at a dose in the range of about 0.1 mg to about 0. 3 mg, day 7, 8, or 9 at a dose in the range of about 0.2 mg to about 0.4 mg, day 14, 15, or 16 at a dose in the range of about 0.8 mg to about 1 .2 mg, and day 21 , 22, or 23 at a dose in the range of about 1 .3 mg to about 1.6 mg. Cycles 2-23 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .5 mg once every two weeks. Alternatively, the target dose is 1 .0. mg, and cycles 2-24 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .0 mg once every two weeks. Each cycle is optionally 28 days. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0025] In an embodiment, the anti-STEAP1 antigen binding protein is administered in six cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1 .0 mg, and day 22 at 1 .5 mg. Cycles 2-6 each comprise administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two32512 / 70538 weeks. In an embodiment, Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1.0 mg, and day 22 at 1.0 mg. Cycles 2-6 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .0 mg once every two weeks. In embodiment, the six cycles are repeated as a maintenance therapy (i.e., in the absence of progression or biochemical recurrence). In an embodiment, the six cycles are repeated until an optimal PSA nadir (e.g., < 2 ng / mL) has been achieved. In an embodiment, the patient has a biochemical recurrence and the anti- STEAP1 antigen binding protein is administered for an additional six cycles. In an embodiment, the anti-STEAP1 antigen binding protein is administered for an additional nine cycles. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0026] In another aspect, the anti-STEAP1 antigen binding protein is administered in 12 cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1.0 mg, and day 22 at 1.5 mg. Cycles 2-12 each comprise administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks. In an embodiment, Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1 .0 mg, and day 22 at 1 .0 mg. Cycles 2-12 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .0 mg once every two weeks. Each cycle is optionally 28 days. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo32512 / 70538 metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0027] In another aspect, the anti-STEAP1 antigen binding protein is administered in 24 cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, day 15 at 1 .0 mg, and day 22 at 1 .5 mg. Cycles 2-24 each comprise administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks. In an embodiment, Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1 .0 mg, and day 22 at 1 .0 mg. Cycles 2-24 each comprise administering the anti-STEAP1 antigen binding protein at about 1 .0 mg once every two weeks. Each cycle is optionally 28 days. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk BCR of nonmetastatic castrationsensitive prostate cancer. In an embodiment, the prostate cancer is localized prostate cancer. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig.

[0028] The disclosure further provides a method of treating a patient having prostate cancer, comprising administering to the patient a pharmaceutical composition comprising xaluritamig over the course of at least two 28 day cycles, wherein (i) Cycle 1 comprises administering about 0.1 mg to about 0.3 mg of xaluritamig on day 1 or day 2, administering about 0.2 mg to about 0.4 mg of xaluritamig on day 7, 8, or 9, administering about 0.8 to about 1.2 mg of xaluritamig on day 14, 15, or 16 and administering about 1.3 to about 1.6 mg of xaluritamig on day 21 , 22, or 23 followed by one or more additional cycles (Cycle 2) comprising administering 1 .5 mg of xaluritamig once per two weeks. The disclosure further provides a method of treating a patient having prostate cancer, comprising administering to the patient a pharmaceutical composition comprising xaluritamig over the course of at least two 28 day cycles, wherein (i) Cycle 1 comprises administering about 0.1 mg to about 0.3 mg of xaluritamig on day 1 or day 2, administering about 0.2 mg to about 0.4 mg of xaluritamig on day 7, 8, or 9, administering about 0.8 to about 1 .2 mg of xaluritamig on day 14, 15, or 16 and administering about 0.8 to about 1 .2 mg of xaluritamig on day 21 , 22, or 23 followed by one or more additional cycles (Cycle 2) comprising administering 1 .0 mg of xaluritamig once per two weeks. The prostate cancer is (a) high-risk biochemical recurrence32512 / 70538 of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer or (c) metastatic hormone sensitive prostate cancer. In various aspects, the patient has localized prostate cancer, and cycle 2 is performed once. Alternatively, the patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, and cycle 2 is performed five times. Alternatively, the patient has hormone castration-sensitive prostate cancer or high-risk BCR, and following cycle 2, the dose of about 1 .0 mg is administered every 4 weeks ten times.

[0029] The disclosure further provides a method of treating a patient having prostate cancer, comprising administering to the patient a pharmaceutical composition comprising xaluritamig over the course of at least two 28 day cycles, wherein (i) Cycle 1 comprises administering about 0.1 mg to about 0.3 mg of xaluritamig on day 1 or day 2, administering about 0.2 mg to about 0.4 mg of xaluritamig on day 7, 8, or 9, administering about 0.75 mg of xaluritamig on day 14, 15, or 16 and administering about 0.75 mg of xaluritamig on day 21 , 22, or 23 followed by one or more additional cycles (Cycle 2) comprising administering 0.75 mg of xaluritamig once per two weeks. The prostate cancer is (a) high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer or (c) metastatic hormone sensitive prostate cancer. In an embodiment, the patient has localized prostate cancer, and cycle 2 is performed once. In an embodiment, the patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, and cycle 2 is performed five times.

[0030] The disclosure further provides a method of treating a patient having prostate cancer, comprising administering to the patient a pharmaceutical composition comprising xaluritamig over the course of at least two 28 day cycles, wherein (i) Cycle 1 comprises administering about 0.1 mg to about 0.3 mg of xaluritamig on day 1 or day 2, administering about 0.2 mg to about 0.4 mg of xaluritamig on day 7, 8, or 9, administering about 0.75 mg of xaluritamig on day 14, 15, or 16 and administering about 1 .0 mg of xaluritamig on day 21 , 22, or 23 followed by one or more additional cycles (Cycle 2) comprising administering 1 .0 mg of xaluritamig once per two weeks. The prostate cancer is (a) high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer or (c) metastatic hormone sensitive prostate cancer. In various aspects, the patient has localized prostate cancer, and cycle 2 is performed once. Alternatively, the patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, and cycle 2 is performed five times. Alternatively, the patient has hormone castration-sensitive prostate cancer or high-risk BCR, and following cycle 2, the dose of about 1 .0 mg is administered every 4 weeks ten times.32512 / 70538

[0031] The disclosure further provides a method of treating a patient having prostate cancer, comprising administering to the patient a pharmaceutical composition comprising xaluritamig over the course of at least two 28 day cycles, wherein (i) Cycle 1 comprises administering 0.1 mg of xaluritamig on day 1 , administering 0.3 mg of xaluritamig on day 8, administering 1 .0 mg of xaluritamig on day 15, and administering 1 .5 mg of xaluritamig on day 22, followed by one or more additional cycles (Cycle 2) comprising administering 1 .5 mg of xaluritamig once per two weeks. Alternatively, (i) Cycle 1 comprises administering 0.1 mg of xaluritamig on day 1 , administering 0.3 mg of xaluritamig on day 8, administering 1 .0 mg of xaluritamig on day 15, and administering 1.0 mg of xaluritamig on day 22, followed by one or more additional cycles (Cycle 2) comprising administering 1 .0 mg of xaluritamig once per two weeks Alternatively, (i) Cycle 1 comprises administering 0.1 mg of xaluritamig on day 1 , administering 0.3 mg of xaluritamig on day 8, and administering 1 .0 mg of xaluritamig on day 15, followed by one or more additional cycles (Cycle 2) comprising administering 1.0 mg of xaluritamig once per two weeks or per four weeks. The prostate cancer is (a) high-risk BCR, (b) localized prostate cancer, or (c) metastatic hormone sensitive prostate cancer. In various aspects, the patient has localized prostate cancer, and cycle 2 is performed once.Alternatively, the patient has high-risk biochemical recurrence of nonmetastatic castrationsensitive prostate cancer, and cycle 2 is performed five times. Alternatively, the patient has hormone castration-sensitive prostate cancer or high-risk BCR, and following cycle 2, the dose of about 1 .0 mg is administered every 4 weeks 10 times. In an embodiment, the prostate cancer is biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. In an embodiment, the prostate cancer is metastatic hormone sensitive prostate cancer.

[0032] In an embodiment, the anti-STEAP1 antigen binding protein comprises two Fab domains and one scFv domain, wherein each Fab domain binds a target (e.g., STEAP1 ) and the scFv domain binds another target (e.g., CD3). In an embodiment, the anti-STEAP1 antigen binding protein is an XmAb® 2+1 molecule. An “XmAb® 2+1 ” molecule (used interchangeably with a “multichain T cell engager molecule” or “central-scFv” molecule) contains two Fab domains and one scFv domain, wherein each Fab domain binds a target (e.g., STEAP1 ) and the scFv domain binds another target (e.g., CD3). An XmAb® 2+1 molecule format is shown in Figure 1 .

[0033] In an embodiment, the anti-STEAP1 antigen binding protein comprises two Fab binding domains, wherein each Fab binding domain binds STEAP1 .

[0034] In an embodiment, the anti-STEAP1 antigen binding protein comprises two Fab binding domains, wherein each Fab binding domain binds STEAP1 , and wherein each32512 / 70538Fab binding domain comprises a variable heavy domain, a variable light domain, a CH1 domain, and a constant light domain, wherein the variable heavy domain comprises HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and the variable light domain comprises LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14.

[0035] In an embodiment, the CD3 binding domain of the anti-STEAP1 antigen binding protein is an scFv binding domain.

[0036] In an embodiment, the anti-STEAP1 antigen binding protein comprises an scFv binding domain, wherein the scFv binding domain binds CD3, and wherein the scFv variable heavy domain comprises HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; an scFv linker; and an scFv variable light domain, wherein the scFv variable light domain comprises LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6. In an embodiment, each Fab variable heavy domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO: 15; each Fab variable light domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO: 16; the scFv variable heavy domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO: 8. In an embodiment, each Fab variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15; each Fab variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 16; the scFv variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8. In an embodiment, each Fab variable heavy domain comprises SEQ ID NO: 15 or 20; each Fab variable light domain comprises SEQ ID NO: 16; the scFv variable heavy domain comprises SEQ ID NO:7; and the scFv variable light domain comprises SEQ ID NO: 8. In an embodiment, the scFv binding domain which binds CD3 comprises an scFv linker. In an embodiment, each Fab variable heavy domain comprises SEQ ID NO: 15. In an embodiment, each Fab variable heavy domain comprises SEQ ID NO: 20.

[0037] In an embodiment, the anti-STEAP1 antigen binding protein comprises a first Fc domain and a second Fc domain. In an embodiment, the first Fc domain comprises amino acid substitutions E233P, L235V, G236A, S267K, R292C, N297G, V302C, E357Q, and S364K; and the second Fc domain comprises amino acid substitutions N208D, E233P, L235V, G236A, S267K, R292C, Q295E, N297G, V302C, L368D, K370S, N384D, Q418E, and N421 D (all Ell numbering). In an embodiment, the first Fc domain and the second Fc domain each comprise a deletion at position 234.32512 / 70538

[0038] In an embodiment, the anti-STEAP1 antigen binding protein comprises a HC (heavy chain) comprising SEQ ID NO: 17, a HC with inserted CD3 scFv comprising SEQ ID NO: 19, and two light chains, each comprising SEQ ID NO: 18. In an embodiment, the anti- STEAP1 antigen binding protein comprises a HC comprising SEQ ID NO: 23, a HC with inserted CD3 scFv comprising SEQ ID NO: 26, and two light chains, each comprising SEQ ID NO: 18. In an embodiment, the anti-STEAP1 antigen binding protein is an XmAb® 2+1 molecule.

[0039] In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig. In an embodiment, the anti-STEAP1 antigen binding protein is xaluritamig and comprises a HC (heavy chain) comprising SEQ ID NO: 17, a HC with inserted CD3 scFv comprising SEQ ID NO: 19, and two light chains, each comprising SEQ ID NO: 18.BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1. Schematic of an XmAb® 2+1 molecule, depicting two Fabs that each bind STEAP1 and an scFv that binds CD3.

[0041] Figure 2 is a graph showing that the level of STEAP1 protein expression observed in primary prostate adenocarcinoma was similar to the level of expression observed in metastatic castration-resistant prostate cancer specimens.DETAILED DESCRIPTION

[0042] Xaluritamig is an XmAb® 2+1 T cell engager (TCE) molecule that is designed to direct T effector cells towards STEAP1 expressing cells. The first-in-human study described herein reports xaluritamig monotherapy for in adult subjects with newly diagnosed localized prostate cancer in a neoadjuvant setting. People with localized prostate cancer may be candidates for surgical resection of the prostate or another local treatment modality such as radiotherapy, contingent upon the staging assessments. Patients who choose surgery as their primary therapy undergo a radical prostatectomy (RP) which is often preceded by a short window period for surgical planning in which no anti-cancer therapy is administered. This window of opportunity would allow the introduction of neoadjuvant administration of an anti-STEAP1 antigen binding protein (e.g., xaluritamig) to attempt to trigger a beneficial anti-tumor immune response. Also described herein is the treatment of patients having biochemical recurrence of nonmetastatic castration-sensitive prostate cancer. STEAP1 is overexpressed in prostate cancer; reduced expression is observed in normal tissues. High expression of STEAP1 is associated with shorter survival time and poor prognosis. Indeed, STEAP1 is differentially expressed in prostate cancer compared to normal tissues (Hubbert et al., PNAS USA, 96:14523-8, 1999). Increased STEAP1 protein32512 / 70538 expression was associated with higher Gleason grade in primary prostate adenocarcinoma specimens (Gomes et al., Urol. Oncol., 32:53. e23-9, 2014) and increased STEAP1 mRNA expression was observed in bone and lymph node metastatic lesions compared to primary prostate cancer samples (Nolan-Stevaux et al., Cancer Discov., 14:90-103, 2024). High STEAP1 protein expression was observed in metastatic castration-resistant prostate cancer (Bhatia et al., Nature Comm., 14:2041 , 2023). These data suggest that STEAP1 overexpression may coincide with later stage or more aggressive and metastatic cancer. Also described herein is the treatment of patients having metastatic hormone sensitive prostate cancer. Patients with poor risk features may benefit from new therapies that can combine with standard of care in this setting.

[0043] Surprisingly, it was observed that STEAP1 is overexpressed in earlier stages of the disease, providing a new therapeutic option for patient subpopulations including patients with high-risk BCR prostate cancer and patients with newly diagnosed localized prostate cancer.

[0044] The term “localized prostate cancer” refers to prostate cancer that is confined to the prostate gland and has not spread to other parts of the body or beyond the prostate capsule. This stage of prostate cancer is typically classified as Stage I or Stage II in the Tumor, Node, Metastasis (TNM) staging system, which describes the size of the tumor, whether there are cancer cells in the lymph nodes, and whether the cancer has spread to a different part of the body (metastasized). In localized prostate cancer, the disease is generally limited to the prostate and may involve varying degrees of tumor growth within the gland, but there is no evidence of distant metastases. (Mottet, N., et al. (2020). European Urology, 79(2), 243-262.)

[0045] The term “metastatic prostate cancer” refers to prostate cancer that has spread to other parts of the body or beyond the prostate capsule. This stage of prostate cancer is typically classified as Stage IV in the Tumor, Node, Metastasis (TNM) staging system, which describes the size of the tumor, whether there are cancer cells in the lymph nodes, and whether the cancer has spread to a different part of the body or metastasized (Conford et al, Eur Urol. 2021 Feb;79(2):263-282).

[0046] Biochemical recurrence (BCR) in non-metastatic castration-sensitive prostate cancer (nmCSPC) is defined as the return of detectable prostate-specific antigen (PSA) levels following primary local treatment (such as radical prostatectomy or radiotherapy) without any evidence of distant metastatic disease on conventional imaging.

[0047] The phrase “high-risk biochemical recurrent prostate cancer” refers to cases where prostate cancer has recurred after initial treatment (typically surgery or radiation therapy) and is characterized by a higher likelihood of progression and adverse outcomes (compared to low-risk BCR). This is usually determined by elevated prostate-specific antigen32512 / 70538(PSA) levels following initial treatment, combined with other clinical factors that indicate a more aggressive form of cancer. The risk is considered high based on criteria such as PSA levels significantly above the normal range, high Gleason scores (which indicate more aggressive cancer), and advanced disease stage at recurrence. (Shore, et al., Prostate Cancer Prostatic Dis 27, 192-201 , 2024). In an embodiment, the patient’s PSA doubles in less than twelve months. If a patient had a radical prostatectomy, elevated PSA is anything >0.2 ng / mL. If a patient had radiation, elevated PSA is anything that is a 2 ng / mL increase over the lowest PSA the patient had after radiation.

[0048] “Neoadjuvant” refers to a therapy given before any definitive treatment. In an embodiment, the methods described herein comprise administering an anti-STEAP1 antigen binding protein (such as xaluritamig), without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.

[0049] “Hormone sensitive” may be used interchangeably with “castration sensitive”. These are prostate cancer patients who have not had disease progression while having a testosterone in castrate range (via either medical or surgical castration).

[0050] In an embodiment, the mHSPC is high-volume mHSPC, which refers to the presence of visceral metastasis and / or > 4 bone metastases with at least one outside of the vertebral column and pelvis. In an embodiment, the mHSPC is de novo mHSPC, which refers to metastatic disease with no prior diagnosis of localized prostate cancer and the patient has started ADT (LHRH agonist / antagonist or orchiectomy) with or without ARPI (abiraterone OR darolutamide) no longer than 12 weeks before screening.

[0051] In an embodiment, a patient having mHSPC is not being administered enzalutamide or apalutamide when administered a first dose of an anti-STEAP1 antigen binding protein.

[0052] In an embodiment, a patient having mHSPC is being administered abiraterone or darolutamide when administered a first dose of an anti-STEAP1 antigen binding protein.

[0053] Cytokine release syndrome may result from T-cell engager therapy.

[0054] Cytokine release syndrome can occur with activation of bystander immune and nonimmune cells, possibly resulting in comorbidities. CRS may be graded according to Lee et al ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019;25(4):625 638.

[0055] A dosing regimen for an anti-STEAP1 antigen binding protein such as xaluritamig in prostate cancer patients (e.g., high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer patients, localized cancer patients or metastatic hormone-sensitive prostate cancer)) includes step dosing. To help reduce32512 / 70538 cytokine release and to achieve treatment with the active dose of an anti-STEAP1 antigen binding protein (e.g. xaluritamig) safely, the step dosing may include two or three steps, each step being a relatively small dose increase. The priming dose (initial dose) and target dose are also within a relatively narrow range of one another, while demonstrating efficacy in prostate cancer patients. The doses of the anti-STEAP1 antigen binding protein (e.g., xaluritamig) are also relatively low compared to the doses administered in a clinical trial for a bispecific T-cell engager that binds both DLL3 and CD3. Ares et al., J. Clin. Oncol. 2023 Jun 1 ;41 (16):2893-2903 describes that pharmacodynamic responses were greatest after initial administration of 1 -mg step dose of a bispecific T-cell engager that binds both DLL3 and CD3, and that the expansion dose was 100 mg.

[0056] In prostate cancer, several PSMA-targeted TCEs have entered the clinic but have seen limited success due to minimal efficacy, toxicity, and short duration of response (DOR) (see e.g. Sorrentino et al., Cancers (Basel) 2023; 15; Powers et al., J. Hematol Oncol 2020; 13:144; and Tucker et al., Cancer Med 2019;8:4644-55). For example, JNJ- 63898081 , a PSMA and CD3 bispecific antibody, led to transient declines in prostate specific antigen (PSA) with 2 out of 39 (5%) patients experiencing a confirmed PSA50 response and no radiographic responses in a phase 1 study of patients with mCRPC (Lim et al., Clin Genitourin Cancer 2023;21 :366-75). PSMA-targeting TCE HPN424 reported 3 of 63 (5%) patients experiencing a PSA50 response and 1 of 34 (3%) experiencing a confirmed Response Evaluation Criteria in Solid Tumors (RECIST) response with manageable safety (Bono et al., J. Clin. One. 2021 ;39 :5013-13). Combination therapy may further improve efficacy by inducing synergistic effects and / or overcoming mechanisms of resistance. The disclosure contemplates use of xaluritamig in combination with standard of care hormonal and radioligand therapies in patients. In some embodiments, the patient has advanced prostate cancer. In some embodiments, the patient has been treated with ADT. In some embodiments, the patient has received prior treatment with 0 or 1 androgen receptor pathway inhibitors (ARPI).

[0057] While ARPI (e.g., abiraterone, enzalutamide, apalutamide, and darolutamide) and taxanes (e.g., docetaxel and cabazitaxel) are standard of care agents for non-metastatic and / or metastatic, hormone-sensitive prostate cancer, the majority of patients will progress on therapy.

[0058] The disclosure provides a method wherein an anti-STEAP1 antigen binding protein, such as xaluritamig, is administered according to a method of the present disclosure. The present disclosure also provides an anti-STEAP1 antigen binding protein, such as xaluritamig, for use in the treatment of prostate cancer, wherein the anti-STEAP1 antigen binding protein is formulated for administration according to a method of the present32512 / 70538 disclosure. In an embodiment, the dose of anti-STEAP1 antigen binding protein is about 0.001 mg to about 2 mg, about 0.1 mg to about 1 .5 mg, about 0.1 mg to about 2 mg, or about 0.1 mg to about 1 .5 mg. In an embodiment, the dose is 0.1 mg, 0.2 mg, 0.3 mg, 0.4 mg, 0.5 mg, 0.6 mg, 0.7 mg, 0.75, 0.8 mg, 0.9 mg, 1 .0 mg, 1 .1 mg, 1 .2 mg, 1 .3 mg, 1 .4 mg, 1 .5 mg, 1 .6 mg, or 1 .7 mg. In an embodiment, the dose is about 0.1 mg. In an embodiment, the dose is about 0.3 mg. In an embodiment, the dose is about 0.75 mg. In an embodiment, the dose is about 1 mg. In an embodiment, the dose is about 1 .5 mg. In an embodiment, the dose is 0.1 mg. In an embodiment, the dose is 0.3 mg. In an embodiment, the dose is 0.75 mg. In an embodiment, the dose is 1 mg. In an embodiment, the dose is 1 .5 mg. In an embodiment, the dose is administered once per one week. In an embodiment, the dose is administered once per two weeks. In an embodiment, the dose is administered once per three weeks. In an embodiment, the dose is administered once per four weeks. In an embodiment, the dose is administered by intravenous administration. In an embodiment, the dose is administered once per week beginning in cycle 1 . In an embodiment, the dose is administered once per week beginning in cycle 2. In an embodiment, the dose is administered once per two weeks beginning in cycle 2. In an embodiment, the dose is administered once per three weeks beginning in cycle 2. In an embodiment, the dose is administered once per four weeks beginning in cycle 2. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per two weeks beginning on day one of cycle 2. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per two weeks once the target dose has been achieved. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per three weeks once the target dose has been achieved. In an embodiment, the dose is administered once per week for the first cycle, and then administered once per four weeks once the target dose has been achieved.

[0059] In an embodiment, six cycles of administrations are provided to the patient. For instance, a dose of anti-STEAP1 antigen binding protein (e.g., any of the doses described above) is administered once per week for the first cycle, and then a dose of anti- STEAP1 antigen binding protein is administered once per two weeks once for cycles 2 through 6. Alternatively, after the first cycle is completed, a dose of anti-STEAP1 antigen binding protein is administered once every two weeks for cycles 2 through 11 (or for cycles 2 through 12), resulting in a total of 12 cycles of administrations. Alternatively, after the first cycle is completed, a dose of anti-STEAP1 antigen binding protein is administered once per two weeks for cycles 2 and then a dose of anti-STEAP1 antigen binding protein is administered once per four weeks for cycles 3 through 12, resulting in a total of 12 cycles of administration.32512 / 70538

[0060] In an embodiment, twelve cycles of administration are provided to the patient. For instance, a dose of anti-STEAP1 antigen binding protein (e.g., any of the doses described above) is administered once per week the first three weeks of the first cycle, then a dose of anti-STEAP1 antigen binding protein is administered once per two weeks once for cycles 2 and then a dose of anti-STEAP1 antigen binding protein is administered once per four weeks once for cycles 3 through 12. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormonesensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer.

[0061] In an embodiment, the anti-STEAP1 antigen binding protein is administered by step dosing, wherein multiple doses are administered in increasing amounts. In this regard, the anti-STEAP1 antigen binding protein may be administered such that the dose administered is increased in two steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen binding protein is administered such that the dose is increased in three steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen binding protein is administered on day 1 at 0.1 mg, day 8 at 0.3 mg, day 15 at 1.0 mg, and day 22 at 1 .5 mg (a representative “step dosing cycle”). Alternatively, in an embodiment, , the anti-STEAP1 antigen binding protein is administered on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1.0 mg, (a representative “step dosing cycle”). In an embodiment, the method further comprises administering to the patient a dose of an anti-STEAP1 antigen binding protein once per week, once per two weeks, once per three weeks, or once per four weeks after administration of the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 .5 mg once every two weeks or every three or every four weeks after the step dosing cycle. Alternatively, the anti-STEAP1 antigen binding protein is administered at 1 .0 mg every two or every three or every four weeks after the step dosing cycle.

[0062] In an embodiment, the anti-STEAP1 antigen binding protein is administered by step dosing, wherein multiple doses are administered in increasing amounts. In this regard, the anti-STEAP1 antigen binding protein may be administered such that the dose administered is increased in two steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen binding protein is administered such that the dose is increased in three steps (i.e., multiple doses are administered with two increases in dosing). In an embodiment, the anti-STEAP1 antigen32512 / 70538 binding protein is administered on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1.0 mg, (a representative “step dosing cycle”). In an embodiment, the method further comprises administering to the patient a dose of an anti-STEAP1 antigen binding protein once per week, once per two weeks, once per three weeks, or once per four weeks after administration of the step dosing cycle. In an embodiment, the anti-STEAP1 antigen binding protein is administered at 1 .0 mg once every four weeks after the step dosing cycle. In an embodiment, the prostate cancer is metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is de novo metastatic hormone-sensitive prostate cancer. In an embodiment, the metastatic hormone-sensitive prostate cancer is high-volume de novo metastatic hormone-sensitive prostate cancer.

[0063] In an embodiment, the anti-STEAP1 antigen binding protein is administered in two cycles. In an embodiment, the first cycle comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, day 15 at 1.0 mg, and day 22 at 1 .5 mg. The second cycle comprises administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks after cycle 1 is completed. In various aspects, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1.5 mg once every two weeks for 3 months after cycle 1 is completed. In various aspects, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks for five months after cycle 1 is completed. In an embodiment, cycle 2 comprises administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks for 11 months after cycle 1 is completed. Optionally, the cycles are 28 days in length.

[0064] In an embodiment, the anti-STEAP1 antigen binding protein is administered in six cycles. Cycle 1 comprises administering the anti-STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, day 15 at 1.0 mg, and day 22 at 1.5 mg. Cycles 2-6 each comprise administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks. In another aspect, the anti-STEAP1 antigen binding protein is administered in 12 cycles. In another aspect, the anti-STEAP1 antigen binding protein is administered at a dose of 1 .0 mg for cycles 2 and beyond. Alternatively, Cycle 1 comprises administering the anti- STEAP1 antigen binding protein on day 1 at 0.1 mg, day 8 at 0.3 mg, and day 15 at 1 .0 mg, and day 22 at 1.5 mg. Cycles 2-12 each comprise administering the anti-STEAP1 antigen binding protein at 1 .5 mg once every two weeks, once every three weeks, or once every four weeks. Each cycle is optionally 28 days. In some embodiments, Cycles 2-12 each comprise administering the anti-STEAP1 antigen binding protein at 1 .0 mg once every two weeks, once every three weeks, or once every four weeks. Each cycle is optionally 28 days.32512 / 70538

[0065] The disclosure provides a method wherein an anti-STEAP1 antigen binding protein, such as xaluritamig, is administered according to a method of the present disclosure, optionally in combination with other agent(s) including abiraterone, enzalutamide, cabazitaxel, darolutamide, apalutamide, PSMA antibody drug conjugates, B7H3 antibody drug conjugates, radiotherapy and / or standard of care therapies for prostate cancer. The present disclosure also provides an anti-STEAP1 antigen binding protein, such as xaluritamig, for use in the treatment of prostate cancer, wherein the anti-STEAP1 antigen binding protein is formulated for administration according to a method of the present disclosure, optionally in combination with another agent(s) including abiraterone, enzalutamide, cabazitaxel, darolutamide, apalutamide, PSMA antibody drug conjugates, B7H3 antibody drug conjugates, radiotherapy and / or standard of care therapies for prostate cancer.

[0066] Abiraterone is a cytochrome P450 (CYP) 17 inhibitor indicated in combination with prednisone (or prednisolone in some regions) for the treatment of patients with mCRPC and, in some regions, metastatic or high risk castration-sensitive prostate cancer (CSPC). Disease relapse following abiraterone may result from increased androgen receptor expression (e.g., androgen receptor amplification), among other mechanisms (Galletti et al, Cancer Treat Rev. 2017 Jun;57:16-27). In various aspects, the method of the disclosure further comprises administering abiraterone at a dose of 1000 mg orally, once daily. Optionally, the method further comprises administering prednisone to the patient at a dose of 5 mg, twice daily. In various aspects, the method comprises administering prednisolone to the patient at a dose of 10 mg orally, once daily.

[0067] Darolutamide is an androgen receptor (AR) inhibitor with a flexible polar- substituted pyrazole structure that binds with high affinity directly to the receptor ligand binding domain (Leibowitz-Amit and Joshua, 2012; Fizazi et al., 2013; Moilanen et al., 2013). Darolutamide competitively inhibits androgen binding, AR nuclear translocation, and AR mediated transcription. A major metabolite, keto-darolutamide, exhibited similar in vitro activity to darolutamide. Darolutamide treatment decreases prostate tumor cell proliferation leading to potent antitumor activity. It inhibits binding of androgens to AR, restricts the AR to the cytoplasm of cells, inhibiting AR-mediated transcription involved in prostate cancer progression.

[0068] Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors; and consequently, inhibits nuclear translocation of androgen receptors and their interaction with DNA. Enzalutamide is indicated for the treatment of patients with CRPC and, in some regions, metastatic hormone sensitive prostate cancer. Disease relapse following enzalutamide is due in part to32512 / 70538 mutations in androgen receptor (like AR V7) and increased androgen receptor expression (e.g., androgen receptor amplification), among other mechanisms (Galletti et al, supra). It is also envisioned that the anti-STEAP1 antigen binding protein (e.g., xaluritamig) may be administered without concurrent ADT.

[0069] An anti-STEAP1 antigen binding protein (or a STEAP1 antigen binding protein) is a molecule that binds human STEAP1 . Such molecule may further bind another target, such as a cell surface antigen such as CD3. Non-limiting examples of formats for such molecules include antibodies (including bispecific antibodies) and fragments thereof and T cell engager molecules including molecules in the XmAb® 2+1 format and bispecific T-cell engager molecules.

[0070] An anti-STEAP1 antigen binding protein binds to its targets when, for example, it binds with a dissociation constant (KD) of <10-7M as measured via a surface plasma resonance technique (e.g., BIACore, GE-Healthcare Uppsala, Sweden) or Kinetic Exclusion Assay (KinExA, Sapidyne, Boise, Idaho).

[0071] An example of an anti-STEAP1 antigen binding protein is xaluritamig. A further description of xaluritamig can be found in PCT Publication No. WO 2020 / 010079, which is herein incorporated by reference in its entirety.

[0072] Bispecific T-cell engager molecules are recombinant protein constructs made from two flexibly linked antibody derived binding domains. A “bispecific T-cell engager molecule” includes a “BiTE® molecule”. One binding domain of bispecific T-cell engager is specific for a selected tumor-associated surface antigen on target cells; the second binding domain is specific for CD3, a subunit of the T cell receptor complex on T cells. By their particular design, bispecific T-cell engager molecules are uniquely suited to transiently connect T cells with target cells and, at the same time, potently activate the inherent cytolytic potential of T cells against target cells (Yang, Fa; Wen, Weihong; Qin, Weijun (2016). “Bispecific Antibodies as a Development Platform for New Concepts and Treatment Strategies”. International Journal of Molecular Sciences. 18 (1): 48 (2016)). A bispecific T- cell engager molecule is bispecific, meaning that it binds two targets on two different types of cells (target antigen such as STEAP1 on a target cell and CD3 on a T cell) at the same time.

[0073] As used herein, an “XmAb® 2+1 ” molecule (used interchangeably with a “multichain T cell engager molecule” or “central-scFv” molecule) contains two Fab domains and one scFv domain, wherein each Fab domain binds a target (e.g., STEAP1) and the scFv domain binds another target (e.g., CD3). An XmAb® 2+1 molecule format is shown in Figure 1 . The scFv domain (e.g., that binds CD3) is inserted between an Fc domain and a CHI-Fv region, thus providing a third antigen binding domain (e.g., two Fabs, each that bind STEAP1 , and one scFv that binds CD3). The anti-CD3 scFv is “inserted” in the HC, meaning the scFv is connected by a linker in the HC. In this embodiment, one polypeptide comprises32512 / 70538 a first heavy chain comprising a first variable heavy domain, a CH1 domain (and optional linker / hinge) and Fc domain, with a scFv comprising a scFv variable light domain, an scFv linker and a scFv variable heavy domain. The scFv is covalently attached between the C- terminus of the CH1 domain of the heavy constant domain and the N-terminus of a first Fc domain using optional domain linkers (VH1 -CH1 - [optional domain linker] -VH2-scFv linker- VL2 - [optional domain linker including the hinge] -CH2-CH3, or the opposite orientation for the scFv, VH1 -CH1 -[optional domain linker] -VL2-scFv linker- VH2- [optional domain linker including the hinge] -CH2- CH3). In some embodiments, the first polypeptide is VH1 - CH1 - domain linker- VH2-scFv linker- VL2-domain linker-CH2-CH3. The other polypeptide is a standard Fab (i.e., VH1 -CH1 -domain linker (e.g., hinge)-CH2-CH3). This embodiment further utilizes two light chains each comprising a variable light domain and a constant light domain, which associate with the heavy chains to form two identical Fabs that bind a target. In particular embodiments, a STEAP1 Fab CD3 scFv central-scFv molecule (or a STEAP1 Fab CD3 scFv XmAb® 2+1 molecule) comprises two Fab domains, each that bind STEAP1 Fab, and an scFv that binds CD3 scFv. In some embodiments, the central-scFv or XmA®b 2+1 molecule is xaluritamig.

[0074] In various aspects of the disclosure, the anti-STEAP1 antigen binding protein comprises two Fab binding domains, wherein each Fab binding domain binds STEAP1 , and wherein each Fab binding domain comprises a variable heavy domain, a variable light domain, a CH1 domain, and a constant light domain, wherein the variable heavy domain comprises HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and the variable light domain comprises LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14. The anti-STEAP1 antigen binding protein further comprises an scFv binding domain which binds CD3 and comprises an scFv variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; an scFv linker; and an scFv variable light domain comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6. In various aspects, each Fab variable heavy domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO: 15 or 20; each Fab variable light domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO: 16; the scFv variable heavy domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90%, 95%, or 99% identical to SEQ ID NO: 8. For instance, each Fab variable heavy domain may comprise SEQ ID NO: 15 or 20; each Fab variable light domain may comprise SEQ ID NO: 16; the scFv variable heavy domain may comprise SEQ ID NO:7; and the scFv variable light domain may comprise SEQ32512 / 70538ID NO: 8. The anti-STEAP1 antigen binding protein may further comprise a first Fc domain and a second Fc domain. In various aspects, the anti-STEAP1 antigen binding protein comprises a heavy chain (HCP comprising SEQ ID NO: 17 or 23, a HC with inserted CD3 scFv comprising SEQ ID NO: 19 or 26, and two light chains (LC), each comprising SEQ ID NO: 18.

[0075] For all positions discussed in the disclosure that relate to antibodies and other antigen-binding proteins, unless otherwise noted, amino acid position numbering is according to the Ell index. The EU index or EU index as in Kabat or EU numbering scheme refers to the numbering of the EU antibody (Edelman et al., 1969, Proc Natl Acad Sci USA 63:78-85, hereby entirely incorporated by reference).

[0076] In exemplary aspects, a molecule of the present disclosure comprises a sequence comprising a C-terminal lysine, as in SEQ ID NOs: 17 or 19. In preferred aspects, the antigen binding protein comprises one or both HC without the C-terminal lysine, as in SEQ ID NOs: 22 and 25. In addition, the HC or HCVR N-terminal glutamine and / or the N- terminal glutamic acid may be converted to pyroglutamic acid, as in SEQ ID NOs: 20, 21 , 23, and 24. In addition, the HC N-terminal glutamine and / or the N-terminal glutamic acid may be converted to pyroglutamic acid, and the sequence may lack a C-terminal lysine, as in SEQ ID NOs: 23 and 26. All forms are envisioned for the antigen binding proteins of the present disclosure.

[0077] A first Fc domain and a second Fc domain each refer to one half of an Fc (fragment crystallizable) region. An Fc region comprises two CH2 domains and two CH3 domains. Therefore, a first Fc domain and a second Fc domain each comprise a CH2 domain and a CH3 domain.

[0078] The anti-STEAP1 antigen binding protein is generally administered to the patient in a pharmaceutical composition, which can include pharmaceutically-acceptable carriers, excipients, or diluents. “Pharmaceutically-acceptable” refers to molecules, compounds, and compositions that are non-toxic to human recipients at the dosages and concentrations employed and / or do not produce allergic or adverse reactions when administered to humans. In certain embodiments, the pharmaceutical composition may contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In such embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCI, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as32512 / 70538 caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-betacyclodextrin); fillers; monosaccharides; disaccharides; and other carbohydrates (such as glucose, mannose or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate 80, triton, tromethamine, lecithin, cholesterol, tyloxapal); stability enhancing agents (such as sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride, mannitol, or sorbitol); delivery vehicles; diluents; excipients and / or pharmaceutical adjuvants. Methods and suitable materials for formulating molecules for therapeutic use are known in the pharmaceutical arts, and are described, for example, in REMINGTON’S PHARMACEUTICAL SCIENCES, 18th Edition, (A.R. Genrmo, ed.), 1990, Mack Publishing Company. In some embodiments, the selection of carriers and excipients for incorporation into the pharmaceutical compositions influences the physical state, stability, rate of in vivo release and rate of in vivo clearance of the anti-STEAP1 antigen binding protein.

[0079] An anti-STEAP1 antigen binding protein, such as xaluritamig, may be formulated as a pre-lyophilized formulation, such as a pre-lyophilized formulation of 0.3 mg / mL to 2.5 mg / mL xaluritamig (e.g., 1 mg / mL) formulated with 10 mM glutamic acid, 9% (w / v) sucrose, 0.01% (w / v) polysorbate 80, pH 4.20 (i.e., xaluritamig is present in a formulation comprising 0.3 mg / mL to 2.5 mg / mL xaluritamig (e.g., 1 mg / mL), 10 mM glutamic acid, 9% (w / v) sucrose, 0.01% (w / v) polysorbate 80, pH 4.20, which is lyophilized). Formulations for an anti-STEAP1 antigen binding protein are also disclosed in PCT Publication No. WO 2019 / 157340, which is herein incorporated by reference in its entirety.

[0080] The present disclosure also includes kits for treating prostate cancer in a patient in need thereof. In one embodiment, the kit comprises a pharmaceutical composition of an anti-STEAP1 antigen binding protein and packaging material that provides instructions regarding the use of the pharmaceutical compositions. The pharmaceutical composition of the kit may be present in a container, such as a vial or syringe. The pharmaceutical composition may be provided as a solution, suspension, gel, emulsion, solid, crystal, or as a dehydrated or lyophilized powder. In embodiments in which the pharmaceutical composition is provided as a powder, the kit may also comprise diluents (e.g., water, saline, or phosphate-buffer saline) necessary to reconstitute the pharmaceutical composition as well as instructions for preparing the composition for administration.32512 / 70538

[0081] It is intended to be understood that when it referred to herein that a patient is administered a dose of an anti-STEAP1 antigen binding protein that the anti-STEAP1 antigen binding protein is in a pharmaceutical composition.

[0082] In some embodiments, the present disclosure also provides kits comprising a pharmaceutical composition and instructions for using the pharmaceutical composition for delivering a therapeutically effective dose, for example, by IV injection for treating prostate cancer in a patient in need thereof. In embodiments in which the pharmaceutical composition is provided in a lyophilized or dry powder form, the kit may comprise a diluent and instructions for reconstituting the pharmaceutical composition prior to administration.

[0083] An anti-STEAP1 antigen binding protein may be administered by means of “step dosing,” which refers to increasing the dose administered to a patient before reaching the target dose level (see also e.g., Ball et al., MAbs. 2023 Jan-Dec;15(1):2181016). Step dosing may include one, two, three, four, or five steps (i.e., administration of multiple doses increasing in the amount of therapeutic administered). Each “step” is an increase in the dose administered to the patient from the last dose administered to the patient. Step dosing may include two or three steps. Step dosing may include two steps to reach a target dose of such as 0.75 mg. Step dosing may include three steps to reach a target dose of such as 1 .5 mg. Step dosing may be implemented to reduce the incidence of cytokine release syndrome. For example, step dosing might begin with a priming dose on cycle 1 day 1 and escalating on day 8 (one step) and continuing at the target dose thereafter. At the conclusion of step dosing, the target dose may be administered (e.g., once per week, once per two weeks, once per three weeks, or once per four weeks). The target dose may be administered at any interval over a desired period of time (e.g., four weeks, five months, or eleven months), providing an overall treatment period of, e.g., two months, six months, or twelve months.

[0084] The anti-STEAP1 antigen binding protein (e.g., xaluritamig) may be first administered by step dosing and then reach the target dose of anti-STEAP1 antigen binding protein (xaluritamig). After reaching the target dose of xaluritamig, a patient may be treated with another therapeutic agent (i.e., combination partner), although the disclosure also contemplates the administration of another therapeutic agent prior to reaching the target dose (e.g., administration on C1 D1). Such another therapeutic agent may be administered in a cycle with xaluritamig.

[0085] A “cycle” refers to the repeating pattern of treatment and may be defined by anti-STEAP1 antigen binding protein (e.g., xaluritamig) or a combination partner. A cycle may also provide the basis for follow-up of patients. A cycle may still be present even when a drug is given continuously. A cycle can include a different number of days depending on the treatment. A cycle refers to a period of time in which the actions that need to be taken can be repeated. It is a standard way of defining treatment duration with defined moments of32512 / 70538 treatment administration. For example, the anti-STEAP1 antigen binding protein (e.g., xaluritamig) cycle may be every 27 days, 28 days, 29 days, 30 days, or 31 days.

[0086] The disclosure provides, in various aspects, a method wherein the anti- STEAP1 antigen binding protein (e.g., xaluritamig) is administered to a patient in need thereof over a course of treatment that comprises two or more cycles, each cycle optionally comprising 27 days, 28 days, 29 days, 30 days, or 31 days. Preferably each cycle comprises 28 days. Cycle 1 comprises a three-step dosing schedule, wherein the patient is administered a dose of 0.1 mg xaluritamig on day 1 (C1 D1), 0.3 mg xaluritamig on day 8 (C1 D8), 1 mg xaluritamig on day 15 (C1 D15), and 1.5 mg xaluritamig on day 22 (C1 D22). In this scenario, 1 .5 mg of xaluritamig is the “target dose.” Alternatively, Cycle 1 comprises a two-step dosing schedule, wherein the patient is administered a dose of 0.1 mg xaluritamig on day 1 (C1 D1 ), 0.3 mg xaluritamig on day 8 (C1 D8), and 1.0 mg xaluritamig on day 15 (C1 D15). In this scenario, 1 .0 mg of xaluritamig is the “target dose.” Following cycle 1 , one or more additional treatment cycles are performed (i.e., cycle 2, cycle 3, etc.), for a desired period of time. In various aspects, cycles 2 and beyond (i.e., each cycle following cycle 1) comprise administration of 1 .5 mg of xaluritamig once every two weeks; for instance, 1 .5 mg of xaluritamig is administered on C2 D1 and 1 .5 mg of xaluritamig is administered on C2 D15. In alternative aspects, cycle 2 may comprise administering xaluritamig once every three weeks (e.g., 1 .5 mg of xaluritamig administered Q3W) or administering xaluritamig once every four weeks (e.g., 1 .5 mg of xaluritamig administered Q4W). Cycle 2 may be repeated one or more times. For instance, cycle 2 may be repeated five times, providing treatment to the patient over the course of six months. Alternatively, cycle 2 may be repeated 11 times, providing treatment to the patient over the course of 12 months. Alternatively, cycle 2 and beyond may comprise of administering 1 .0 mg of xaluritamig. Alternatively, cycle 2 may comprise of administering xaluritamig every 2 weeks and cycles 3 and beyond may comprise of administering xaluritamig every 4 weeks.

[0087] The phrase “with a dose” refers to a dose of a molecule (drug) that can be administered to a patient at the same time (on the same day) as another, different molecule, or administered sequentially (e.g., at least one dose of a molecule administered to a patient is separated in time from at least one dose of another molecule administered to the patient). It is also contemplated herein that a dose of a molecule may be followed by at least one additional dose of the same molecule, followed by at least one dose of a different molecule.

[0088] Generally, IV medications may be administered together on the same day. Administration of oral medication and IV medication may also be administered on the same day. For example, xaluritamig and abiraterone may be administered together on the same day. Medications may also be administered on separate days.32512 / 70538

[0089] As used interchangeably herein, “treatment” and / or “treating” and / or “treat” are intended to refer to all processes wherein there may be a slowing, interrupting, arresting, controlling, stopping, or reversing of the progression of the disorders described herein, but does not necessarily indicate a total elimination of all disorder symptoms. Treatment includes administration of an anti-STEAP1 antigen binding protein for treatment of a disease or condition in a human that would benefit from activity of an anti-STEAP1 antigen binding protein, such as prostate cancer, and includes: (a) inhibiting further progression of the disease; and / or (b) relieving the disease, i.e., causing regression of the disease or disorder or alleviating symptoms or complications thereof.

[0090] The present disclosure contemplates a method of the present invention used to reduce the size of the patient’s prostate tumor. In an embodiment, the tumor is reduced by at least 10%. In an embodiment, the tumor is reduced by at least 20%. In an embodiment, the tumor is reduced by at least 30%. In an embodiment, the tumor is reduced by at least 40%. In an embodiment, the tumor is reduced by at least 50%. In an embodiment, the tumor is reduced by at least 60%. In an embodiment, the tumor is reduced by at least 70%. In an embodiment, the tumor is reduced by at least 80%. In an embodiment, the tumor is reduced by at least 90%. In an embodiment, the tumor is no longer present.

[0091] The present disclosure contemplates a method of the present invention used to reduce the patient’s PSA. The present disclosure contemplates a method of the present invention used to slow or stop the spread of cancer cells to another part(s) of the patient’s body.

[0092] The size of a patient's prostate (and / or metastatic lesions) can be determined by methods known in the art. Such methods include computer tomography (CT), MRI, and / or bone scans. PSA can be determined by a blood test known in the art.

[0093] The term “about” refers to values that are within 10% above or below the referenced value.EXAMPLESEXAMPLE 1 : STEAP1 EXPRESSION

[0094] STEAP1 is differentially expressed in prostate cancer compared to normal tissues (Hubbert et al., PNAS USA, 96:14523-8, 1999). Increased STEAP1 protein expression was associated with higher Gleason grade in primary prostate adenocarcinoma specimens (Gomes et al., Urol. Oncol., 32:53. e23-9, 2014) and increased STEAP1 mRNA expression was observed in bone and lymph node metastatic lesions compared to primary prostate cancer samples (Nolan-Stevaux et al., Cancer Discov., 14:90-103, 2024). High STEAP1 protein expression was observed in metastatic castration-resistant prostate cancer32512 / 70538(Bhatia et al., Nature Comm., 14:2041 , 2023). These data suggest that STEAP1 protein expression would be higher in more aggressive prostate cancer and metastatic prostate cancer.

[0095] To determine STEAP1 protein expression in primary prostate tumors, immunohistochemical staining was done on prostate tumor tissues with an anti-STEAP1 antibody. Formalin-fixed paraffin embedded tumor specimens were stained using the Benchmark ULTRA staining platform. Tissue sections were incubated with rabbit monoclonal anti-STEAP1 primary antibody (clone D8B2V, 1 :100 dilution) or rabbit IgG control. Primary antibodies were detected using the OptiView DAB IHC Detection Kit.

[0096] Surprisingly, and conversely to the published mRNA levels described above, STEAP1 protein expression observed in primary prostate adenocarcinoma was similar to that observed in metastatic castration-resistant prostate cancer specimens, suggesting that targeting STEAP1 in earlier prostate cancer disease settings would be beneficial. See Figure 2.EXAMPLE 2: PHASE 1 B CLINICAL STUDY OF NEOADJUVANT XALURITAMIG IN SUBJECTS WITH NEWLY DIAGNOSED LOCALIZED PROSTATE CANCER

[0097] This is a phase 1 b, open-label, multi-center study to assess the safety, tolerability, and feasibility of xaluritamig as monotherapy in adult patients with newly diagnosed localized intermediate or high-risk prostate cancer in the neoadjuvant setting.

[0098] The study will consist of a 28-day screening period, an 8-week treatment period (equating to two cycles of xaluritamig), a safety follow-up visit, and a long-term followup period.

[0099] Approximately 40 subjects will be enrolled in the study. The duration of enrollment is expected to be approximately 18 months with a subsequent treatment and follow-up period of 44 months.

[0100] Subjects diagnosed with localized intermediate or high-risk prostate cancer with planned radical prostatectomy, will enter a 28-day screening period to determine eligibility for study entry. Enrolled subjects will receive two cycles of xaluritamig and will receive the last dose of xaluritamig approximately 14 to 28 days prior to undergoing radical prostatectomy.

[0101] Xaluritamig will be administered by intravenous (IV) infusion for a total of two cycles consisting of 28 days in each cycle:

[0102] Cycle 1 will be administered once a week (QW) and will include a 3-step dosing schedule to achieve the target dose of 1 .5 mg:-Day 1 : 0.1 mg -Day 8: 0.3 mg32512 / 70538-Day 15: 1.0 mg-Day 22: 1.0 mg

[0103] Cycle 2 will be administered every 2 weeks (Q2W) after completing cycle 1 : -Day 1 : 1 .0 mg -Day 15: 1.0 mg

[0104] The dose level review team (DLRT) will act as a safety review committee and review the safety and tolerability data throughout the study. The first formal review will occur after 10 subjects have been treated and had the opportunity to complete the 2 cycles (8 weeks) of xaluritamig treatment. Upon review of the data, modifications to the dosing regimen and / or monitoring guidelines may be implemented with a DLRT memo. The target dose will not exceed 1 .5 mg, the dosing frequency will not be more frequent than Q2W, and the number of cycles will not exceed 4 without a protocol amendment.

[0105] The xaluritamig end of treatment (EOT) visit should occur after the completion of therapy (e.g., after the completion of cycle 2) and prior to the scheduled surgery for the evaluation of adverse events, the collection of laboratory samples and multi-parametric magnetic resonance imaging (mpMRI). In subjects who discontinue xaluritamig before completing the second cycle, the xaluritamig EOT visit should occur no later than 14 days after the last date of IV administration and before radical prostatectomy.

[0106] Xaluritamig will be administered by intravenous (IV) infusion for a total of two cycles consisting of 28 days in each cycle.

[0107] The decision to proceed to radical prostatectomy, and the timing of the radical prostatectomy, is at the discretion of the urologic surgeon, ideally within 2 to 4 weeks of completing xaluritamig. There will be no additional administration of xaluritamig during or following the surgery. Tissue from the radical prostatectomy will be collected for pathological analysis and for use in translational studies.

[0108] In addition to the follow-up visits listed above, subjects who do not receive radical prostatectomy will receive a SFU visit at approximately 30 (+3) days after receiving the last dose of xaluritamig. For subjects who undergo radical prostatectomy, the SFU will occur approximately 42 (± 7) days after completion of the surgery. The SFU visit will occur regardless of administration of subsequent anti-cancer therapy within that period.

[0109] In addition, all enrolled subjects who undergo radical prostatectomy will be evaluated at 90 (+7) days after the surgery for identification of surgically related adverse events according to Clavien-Dindo classification (Clavien et al, 2009).[001 10] All enrolled subjects will enter LTFU for up to 44 months from the first dose of xaluritamig, or until withdrawal of consent, loss to follow-up or death, whichever occurs first. The first LTFU visit will occur 90 (+7) days after completion of the radical prostatectomy surgery. Subjects that do not proceed with the radical prostatectomy will begin the LTFU32512 / 70538 period 90 (+7) days after the completion of the SFU visit. Long-term follow-up visits will continue every 3 months (± 7 days) during the first year, every 6 months (± 7 days) during the second year and annually thereafter.[0011 1 ] Primary endpoints include treatment-emergent and -related adverse events, and change in clinical and laboratory parameters, received radical prostatectomy after completing xaluritamig treatment and complications of radical prostatectomy according to Clavien-Dindo classification.

[0112] Key secondary endpoints include:-PK;-change in prostate-specific antigen (PSA) levels from baseline to end of xaluritamig treatment;-imaging-based response on multi-parametric magnetic resonance imaging (mpMRI) (prostate imaging-reporting and data system [PI-RADS] change) prior to radical prostatectomy;-pathological complete response (pCR) and minimal residual disease (MRD) following radical prostatectomy;-rise to PSA > 0.2 mg / mL post-radical prostatectomy;-time to PSA rise > 02 ng / mL post-radical prostatectomy;-undetectable PSA at SFU;- PSA progression-free survival (PFS) at year 1 , year 2, year 3 post-radical prostatectomy.

[0113] Key inclusion criteria:

[0114] (1) adult men with histologically, or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features. Intermediate- or high-risk localized prostate cancer, defined as:-Gleason score of 4+3 or higher and initial prostate-specific antigen (iPSA) > 10 ng / mL or;-Clinically advanced 9cT3) on magnetic resonance imaging (MRI) imaging obtained within 3 months prior to screening and / or;-Positive locoregional lymph nodes as detected by prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) scans or < 5 local lymph nodes on MRI can be enrolled.(2) Subjects planned to undergo radical prostatectomy.(3) Subject must have undergone a gallium-68 prostate-specific membrane antigen (68Ga-PSMA-11) or a piflufolastat F 18 PET (computer tomography [CT] or MRI) scan within 3 months prior to screening as part of the standard of care.32512 / 70538(4) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

[0115] Key exclusion criteria include:(1) Subjects with M1a lymph nodes as identified by any imaging modality or T4 tumors.(2) Prior treatment for subject’s prostate cancer.(3) Any evidence of metastases outside of the surgical resection field identified by conventional imaging or PSMA-PET scans.(4) Prior major surgery within 4 weeks of first dose.(5) subjects having a known sensitivity to any of the components of xaluritamig to be administered or supportive agents (e.g., dexamethasone, tocilizumab).EXAMPLE 3: PHASE 1 B CLINICAL STUDY OF NEOADJUVANT XALURITAMIG IN SUBJECTS WITH HIGH-RISK BIOCHEMICAL RECURRENCE OF NONMETASTATIC CASTRATION-SENSITIVE PROSTATE CANCER AFTER DEFINITIVE THERAPY

[0116] This is a phase 1b, open-label, multi-center study to assess the safety, tolerability, feasibility, as well as efficacy of xaluritamig as monotherapy in adult patients with high-risk biochemical recurrence (BCR) nonmetastatic castration-sensitive prostate cancer (nmCSPC) following definitive therapy.

[0117] The study will consist of a 28-day screening period, a treatment period, a safety follow-up visit, and a long-term follow-up period.

[0118] Xaluritamig will be administered as a short-term intravenous (IV) infusion for a total of 6 cycles. One treatment cycle consists of 28 days.

[0119] Cycle 1 will be administered once a week (QW) and will include a 3-step dosing schedule to achieve the target dose of 1 .5 mg:Day 1 : 0.1 mgDay 8: 0.3 mgDay 15: 1.0 mg

[0120] Cycles 2 through 6 will be administered every 2 weeks (Q2W) after completing cycle 1 :Day 1 : 1 .0 mgDay 15: 1.0 mg

[0121] The dose level review team (DLRT) will act as a safety review committee and review the safety and tolerability data after 10 subjects, and again after 20 subjects, have been treated and had the opportunity to complete 2 cycles (8 weeks) of xaluritamig treatment. Upon review of the data, possible modifications to dosing regimen and / or32512 / 70538 monitoring guidelines may be recommended. If the dosing interval is extended to more than Q2W for the target dose at any given cycle, the cycle length will be extended to capture 2 doses (e.g. cycle length for every 4 week [Q4W] will be 56 days).

[0122] Xaluritamig treatment will continue for 6 cycles unless the subject discontinues for an adverse event, the investigator deems that there is an urgent need to proceed to subsequent therapy, disease progression, withdrawal of consent or decision by the investigator to remove the subject from treatment.

[0123] The end of treatment (EOT) visit will occur after the EOT cycle 6. If a subject discontinues xaluritamig early, the EOT visit should occur as soon as possible (within 14 days) after the last dose.

[0124] Subjects will be followed for safety with a SFU visit performed approximately 30 (+3) days after the end of last dose of xaluritamig. The SFU visit will occur regardless of administration of subsequent anticancer therapy within that period.

[0125] Subjects will be in LTFU for up to 36 months from the first dose of xaluritamig (cycle 1 day 1) or until withdrawal of consent, loss to follow-up or death, whichever occurs first. The LTFU visit will occur every 3 months (±7 days) from the SFU visit.

[0126] Primary endpoints include treatment-emergent and -related adverse events, and change in clinical and laboratory parameters.

[0127] Key secondary endpoints include:-PK;-Time to prostate-specific antigen (PSA) progression;-PSA response (PSA 50, PSA 90);-Duration of PSA response (PSA 50 DOR, PSA 90 DOR);-Time to initiation of androgen deprivation therapy or androgen receptor directed therapy;-Time to first use of new anticancer therapy;-Time to metastatic disease / progression;-Time to symptomatic progression;-Time to first symptomatic skeletal event;-Metastasis-free survival (MFS) at 12, 24, and 36 months.

[0128] Key inclusion criteria include:(1) adult male with histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features.(2) Prostate cancer initially treated by radical prostatectomy (RP) or radiotherapy (XRT) (including brachytherapy) or both (e.g., salvage radiotherapy), with32512 / 70538 curative intent.(3) PSA doubling time < 12 months.(4) Subjects must have biochemically recurrent disease after definitive treatment to prostate by either RP or XRT, where BCR is defined as:-Screening PSA by the local laboratory > 1 ng / mL for subject who had RP (with ot without XRT) as primary treatment for prostate cancer or at least 2 ng / mL above the nadir (local assessments) for subjects who had XRT or brachytherapy only as primary treatment for prostate cancer.(5) Subjects must have undergone a68Ga-prostate-specific membrane antigen (PSMA) 11 or a piflufolastat F18 positron emission tomography (PET) scan during or within 3 months of screening.(6) Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

[0129] Key exclusion criteria:(1) Prior hormonal therapy, exceptions include:(i) neoadj uvant / adjuvant therapy to treat prostate cancer < 36 months in duration and > 9 months before study day 1 .(ii) a single dose or a short course (< 6 months) of hormonal therapy given for rising PSA > 9 months before study day 1 .(2) Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer.(3) abiraterone acetate or enzalutamide are allowed if administered in neoadjuvant setting < 36 months in duration and > 9 months before study day 1 .(4) Prior systemic biologic therapy, including immunotherapy for prostate cancer.EXAMPLE 4: PHASE 1 B OPEN-LABEL, MULTICENTER STUDY EVALUATING THE SAFETY, TOLERABILITY, AND EFFICACY OF XALURITAMIG IN COMBINATION WITH ANDROGEN RECEPTOR PATHWAY INHIBITORS IN PARTICIPANTS WITH METASTATIC HORMONE-SENSITIVE PROSTATE CANCER

[0130] This is an open-label, phase 1b, multi-center study valuating the safety, tolerability, and efficacy of xaluritamig in combination with androgen receptor pathway inhibitors (ARPI) in subject with metastatic hormone-sensitive prostate cancer (mHSPC).

[0131] The study will consist of a 28-day screening period, a treatment period, a safety follow-up visit (SFU), and a long-term follow-up (LTFU) period.32512 / 70538

[0132] Approximately 60 subjects will be enrolled in the study. The study duration is expected to be approximately 54 months from the first subject enrolled, with an enrollment duration of approximately 18 months and 36 months treatment and follow-up.

[0133] Subjects > 18 years old with de novo high-volume mHSPC. Subjects must have an adequate organ function and have initiated ADT if not surgically castrated. Subjects diagnosed with de novo high-volume mHSPC, will enter a 28-day screening period to determine eligibility for study entry.

[0134] Subjects will be assigned based on the investigator’s choice to either xaluritamig in combination with darolutamide (arm A) or xaluritamig in combination with abiraterone (arm B). Arm A will include administration of xaluritamig in combination with darolutamide 600 mg BID for 12 cycles. Arm A will include approximately 30 subjects. Xaluritamig will be administered following a step dosing schedule in cycle 1 . Cycle 2 will consist of the target dose of 1 .0 mg being given every 2 weeks (Q2W). Cycle 3 to 12 will consist of the target dose of 1 .0 mg being given every 4 weeks (Q4W). Each cycle is 28 days. Arm A will include safety run-in in approximately 6 subjects, and an expansion in approximately 24 subjects. Arm B will include xaluritamig in combination with abiraterone acetate 1000 mg daily for 12 cycles. Arm B will include approximately 30 subjects. Xaluritamig will be administered following a step dosing schedule in cycle 1 . Cycle 2 will consist of the target dose of 1 .0 mg being given every 2 weeks (Q2W). Cycle 3 to 12 will consist of the target dose of 1 .0 mg being given every 4 weeks (Q4W). Each cycle is 28 days.

[0135] Xaluritamig will be administered as a short-term by intravenous (IV) infusion for a total of twelve treatment cycles. Each cycle consists of 28 days:

[0136] Cycle 1 will be administered once a week (QW) and will include a 3-step dosing schedule to achieve the target dose of 1 .0 mg: -Day 1 : 0.1 mg -Day 8: 0.3 mg -Day 15: 1.0 mg

[0137] Cycle 2 will be administered every 2 weeks (Q2W) (e.g., on days 1 and 15) after completing cycle 1 :-Day 1 : 1.0 mg-Day 15: 1.0 mg

[0138] Cycles 3 to 12 will be administered every 4 weeks (Q4W) (e.g., on day 1 of each cycle) after completing cycle 2:-Day 1 : 1.0 mg32512 / 70538

[0139] Xaluritamig will be administered by intravenous (IV) infusion for a total of twelve cycles consisting of 28 days in each cycle. Upon permanent discontinuation of study treatment (xaluritamig and abiraterone or darolutamide) for any reason, an end of treatment (EOT) visit will be performed as soon as possible (within 14 days) after the last dose of study treatment. If the appropriate SOC therapy is continuation of ADT with ARPI, this should be administered by the discretion of the treating investigator.

[0140] Subjects will be in LTFU for up to 3 years from the first dose of study treatment, or until withdrawal of consent, lost to follow-up, or subject death, whichever occurs first. LTFU will occur every 24 weeks (± 14 days) from the last dose of study treatment. LTFU assessments may include radiographic imaging and collection of prostatespecific antigen (PSA) for subjects without investigator-confirmed radiographic progression of disease. PSA collection should be performed at the frequency outlined in the SOA until investigator-confirmed radiographic progression of disease.

[0141] Primary endpoints include treatment-emergent and -related adverse events and change in clinical and laboratory parameters.

[0142] Secondary endpoints include:-PK of xaluritamig in combination with darolutamide or abiraterone;- Prostate-specific antigen (PSA) < 0.2 ng / mL at 6 months after enrollment;-time to PSA progression;-time to first use of new systemic therapy-time to radiographic progression per Prostate Cancer Working Group 3 (PCWG3) modified Response Evaluation Criteria in Solid Tumors (RECIST) v1 .1 , as assessed by investigator

[0143] Key inclusion criteria:(1) Adult men with histological, pathological, and / or cytological confirmation of adenocarcinoma of the prostate. Mixed histologies (e.g., adenocarcinoma with neuroendocrine component) are not permitted. At the time of diagnosis, must have:-De novo mHSPC, defined as metastatic disease with no prior diagnosis of localized prostate cancer AND started ADT (LHRH agonist / antagonist or orchiectomy) with or without ARPI (abiraterone OR darolutamide) no longer than 12 weeks before screening.-High-volume metastatic disease defined as presence of visceral metastasis and / or > 4 bone metastases with at least one outside of the vertebral column and pelvis-Documented metastatic disease either by a positive bone scan, or for32512 / 70538 soft tissue or visceral metastases, either by contrast enhanced abdominal / pelvic / chest computed tomography (CT) or magnetic resonance imaging (MRI) scan-Prostate-specific antigen (PSA) not progressing per PCWG3 following the initial PSA nadir after starting ADT.(2) Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1(3) Adequate organ function

[0144] Key exclusion criteria include:(1) Prior treatment for prostate cancer with the exception of ADT and / or ARPI;(2) Metastasis in the CNS;(3) Prior treatment with STEAP-1 targeted therapy, radioligand therapy, PARP inhibitors, cytotoxic chemotherapy, aminoglutethimide, ketoconazole or prior systemic biologic therapy (including immunotherapy) for prostate cancer;(4) Prior treatment with enzalutamide or apalutamide within 15days prior enrollment;(5) Prior radiotherapy (except palliative radiation) to the prostate and / or metastatic lesion;(6) Patients suffering from other medical issues and / or requiring medication contraindicated for immunotherapy as defined in the protocol.

[0145] Exemplary embodiments:1 . A method of treating a patient having prostate cancer, comprising administering to a patient having (a) high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer a pharmaceutical composition comprising an anti-STEAP1 antigen binding protein at a dose of about 0.1 mg to about 2.0 mg, the anti-STEAP1 antigen binding protein comprising (i) a STEAP1 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14, and (ii) a CD3 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; and a variable light domain comprising32512 / 70538LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6.2. The method of embodiment 1 , wherein the dose is about 0.1 mg.3. The method of embodiment 1 , wherein the dose is about 0.3 mg.4. The method of embodiment 1 , wherein the dose is about 0.75 mg.5. The method of embodiment 1 , wherein the dose is about 1 mg.6. The method of embodiment 1 , wherein the dose is about 1 .5 mg.7. The method of embodiment 1 , wherein the dose is 1 .5 mg.8. The method of any one of embodiments 1-7, comprising administering the dose once per one week.9. The method of any one of embodiments 1-7, comprising administering the dose once per two weeks.10. The method of any one of embodiments 1-9, comprising administering the anti- STEAP1 antigen binding protein, without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.11 . The method of any one of embodiments 1-10, wherein the anti-STEAP1 antigen binding protein (i) comprises two STEAP1 binding domains that are each Fab binding domains and (ii) the CD3 binding domain is an scFv binding domain.12. The method of any one of embodiments 1-11 , wherein the anti-STEAP1 antigen binding protein comprises a first Fc domain and a second Fc domain.13. The method of any one of embodiments 1-12, wherein the anti-STEAP1 antigen binding protein comprises two Fab domains, each binding STEAP1 , and one scFv domain that binds CD3.14. The method of any one of embodiments 10-13, wherein each Fab variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15 or 20; each Fab variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 16; and the scFv variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8.15. The method of any one of embodiments 10-14, wherein each Fab variable heavy domain comprises SEQ ID NO: 15 or 20; each Fab variable light domain comprises SEQ ID32512 / 70538NO: 16; the scFv variable heavy domain comprises SEQ ID NO:7; and the scFv variable light domain comprises SEQ ID NO: 8.16. The method of any one of embodiments 10-15, wherein the scFv binding domain which binds CD3 comprises an scFv linker.17. The method of any one of embodiments 11-16, wherein the first Fc domain comprises amino acid substitutions E233P, L235V, G236A, S267K, R292C, N297G, V302C, E357Q, and S364K; and the second Fc domain comprises amino acid substitutions N208D, E233P, L235V, G236A, S267K, R292C, Q295E, N297G, V302C, L368D, K370S, N384D, Q418E, and N421 D.18. The method of any one of embodiments 11-16, wherein the first Fc domain and the second Fc domain each comprise a deletion at position 234.19. The method of any one of embodiments 1 -18, wherein the anti-STEAP1 antigen binding protein comprises a heavy chain comprising SEQ ID NO: 17 or 23, a heavy chain with inserted CD3 scFv comprising SEQ ID NO: 19 or 26, and two light chains, each comprising SEQ ID NO: 18.20. The method of any one of embodiments 1-19, wherein the anti-STEAP1 antigen binding protein is xaluritamig.21 . The method of embodiment 20, comprising administering xaluritamig to the patient by step dosing.22. The method of embodiment 20, comprising administering xaluritamig to the patient by step dosing as follows: administering 0.1 mg of xaluritamig on day 1 , administering 0.3 mg of xaluritamig on day 8 administering 1 .0 mg of xaluritamig on day 15, and administering 1 .5 mg of xaluritamig on day 22.23. The method of embodiment 21 or claim 22, further comprising administering xaluritamig to the patient once per two weeks after administration of the step dosing.24. The method of embodiment 21 or claim 22, further comprising administering xaluritamig to the patient once per three weeks or once per four weeks after administration of the step dosing.25. The method of embodiment 23, comprising administering 1 .5 mg xaluritamig to the patient once per two weeks after administration of the step dosing.32512 / 7053826. A method of treating a patient having prostate cancer, comprising administering to a patient having (a) high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer a pharmaceutical composition comprising xaluritamig over the course of at least two 28 day cycles, as follows(i) Cycle 1 : administering 0.1 mg of xaluritamig on day 1 , administering 0.3 mg of xaluritamig on day 8 administering 1.0 mg of xaluritamig on day 15, and administeringl .5 mg of xaluritamig is administered on day 22, followed by one or more of(ii) Cycle 2: administering 1 .5 mg of xaluritamig once per two weeks.27. The method of embodiment 26, wherein patient has localized prostate cancer, and cycle 2 is performed once.28. The method of embodiment 26, wherein patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, and cycle 2 is performed five times.29. The method of any one of embodiments 1-28, comprising administering the anti- STEAP1 antigen binding protein, without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.30. Use of an anti-STEAP1 antigen binding protein in the manufacture of a medicament for treating prostate cancer, wherein the medicament is formulated for administration at a dose of about 0.001 mg to about 2.0 mg, wherein the prostate cancer is (a) high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer, and wherein the anti- STEAP1 antigen binding protein comprises (i) a STEAP1 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14, and (ii) a CD3 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6.32512 / 7053831 . The use of embodiment 30, wherein the dose is about 0.1 mg.32. The use of embodiment 30, wherein the dose is about 0.3 mg.33. The use of embodiment 30, wherein the dose is about 0.75 mg.34. The use of embodiment 30, wherein the dose is about 1 mg.35. The use of embodiment 30, wherein the dose is about 1 .5 mg.36. The use of embodiment 30, wherein the dose is 1 .5 mg.37. The use of any one of embodiments 30-36, wherein the dose is administered once per one week.38. The use of any one of embodiments 30-36, wherein the dose is administered once per two weeks.39. The use of any one of embodiments 30-38, wherein the anti-STEAP1 antigen binding protein is administered, without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.40. The use of any one of embodiments 30-39, wherein the anti-STEAP1 antigen binding protein (i) comprises two STEAP1 binding domains that are each Fab binding domains and (ii) the CD3 binding domain is an scFv binding domain.41 . The use of any one of embodiments 30-40, wherein the anti-STEAP1 antigen binding protein comprises a first Fc domain and a second Fc domain.42. The use of any one of embodiments 30-40, wherein the anti-STEAP1 antigen binding protein is an XmAb® 2+1 molecule.43. The use of any one of embodiments 30-42, wherein each Fab variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15 or 20; each Fab variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 16; and the scFv variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8.44. The use of any one of embodiments 30-43, wherein each Fab variable heavy domain comprises SEQ ID NO: 15 or 20; each Fab variable light domain comprises SEQ ID NO: 16; the scFv variable heavy domain comprises SEQ ID NO:7; and the scFv variable light domain comprises SEQ ID NO: 8.45. The use of any one of embodiments 30-44, wherein the scFv binding domain which binds CD3 comprises an scFv linker.32512 / 7053846. The use of any one of embodiments 30-45, wherein the first Fc domain comprises amino acid substitutions E233P, L235V, G236A, S267K, R292C, N297G, V302C, E357Q, and S364K; and the second Fc domain comprises amino acid substitutions N208D, E233P, L235V, G236A, S267K, R292C, Q295E, N297G, V302C, L368D, K370S, N384D, Q418E, and N421 D.47. The use of any one of embodiments 30-46, wherein the first Fc domain and the second Fc domain each comprise a deletion at position 234.48. The use of any one of embodiments 30-47, wherein the anti-STEAP1 antigen binding protein comprises a heavy chain comprising SEQ ID NO: 17 or 23, a heavy chain with inserted CD3 scFv comprising SEQ ID NO: 19 or 26, and two light chains, each comprising SEQ ID NO: 18.49. The use of any one of embodiments 30-48, wherein the anti-STEAP1 antigen binding protein is xaluritamig.50. The use of embodiment 49, wherein the xaluritamig is administered by step dosing.51 . The use of embodiment 50, wherein xaluritamig is administered to the patient by step dosing as follows:0.1 mg of xaluritamig is administered on day 1 , 0.3 mg of xaluritamig is administered on day 8 1.0 mg of xaluritamig is administered on day 15, and1 .5 mg of xaluritamig is administered on day 22.52. The use of embodiment 50 or embodiment 51 , further comprising administering xaluritamig to the patient once per two weeks after administration of the step dosing.53. The use of embodiment 50 or embodiment 51 , further comprising administering xaluritamig to the patient once per three weeks or once per four weeks after administration of the step dosing.54. The use of embodiment 53, comprising administering 1 .5 mg xaluritamig to the patient once per two weeks after administration of the step dosing.55. An anti-STEAP1 antigen binding protein for use in the treatment of prostate cancer, wherein the anti-STEAP1 antigen binding protein is formulated for administration at a dose of about 0.1 mg to about 2.0 mg.56. The method of any one of embodiments 1-26, or 29, wherein the patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer.32512 / 7053857. The method of any one of embodiments 1-26, or 29, wherein the patient has localized prostate cancer.58. The method of any one of embodiments 1-26, or 29, wherein the patient has metastatic hormone-sensitive prostate cancer.59. The use of any one of embodiments 30-54, wherein the patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer.60. The use of any one of embodiments 30-54, wherein the patient has localized prostate cancer.61 . The use of any one of embodiments 30-54, wherein the patient has localized prostate cancer.32512 / 70538SEQUENCES32512 / 7053832512 / 7053832512 / 70538

Claims

32512 / 70538CLAIMSWhat is claimed:1 . A method of treating a patient having prostate cancer, comprising administering to a patient having (a) high-risk biochemical recurrence of nonmetastatic castrationsensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormonesensitive prostate cancer a pharmaceutical composition comprising an anti-STEAP1 antigen binding protein at a dose of about 0.1 mg to about 2.0 mg, the anti-STEAP1 antigen binding protein comprising (i) a STEAP1 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14, and (ii) a CD3 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6.

2. The method of claim 1 , wherein the dose is about 0.1 mg.

3. The method of claim 1 , wherein the dose is about 0.3 mg.

4. The method of claim 1 , wherein the dose is about 0.75 mg.

5. The method of claim 1 , wherein the dose is about 1 mg.

6. The method of any one of claims 1 -5, comprising administering the dose once per one week.

7. The method of any one of claims 1 -5, comprising administering the dose once per two weeks.

8. The method of any one of claims 1 -7, comprising administering the anti-STEAP1 antigen binding protein, without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.

9. The method of any one of claims 1 -8, wherein the anti-STEAP1 antigen binding protein (i) comprises two STEAP1 binding domains that are each Fab binding domains and (ii) the CD3 binding domain is an scFv binding domain.

10. The method of any one of claims 1 -9, wherein the anti-STEAP1 antigen binding protein comprises a first Fc domain and a second Fc domain.11 . The method of any one of claims 1-10, wherein the anti-STEAP1 antigen binding protein comprises two Fab domains, each binding STEAP1 , and one scFv domain that binds CD3.32512 / 7053812. The method of any one of claims 8-11 , wherein each Fab variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15 or 20; each Fab variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 16; and the scFv variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8.

13. The method of any one of claims 8-12, wherein each Fab variable heavy domain comprises SEQ ID NO: 15 or 20; each Fab variable light domain comprises SEQ ID NO: 16; the scFv variable heavy domain comprises SEQ ID NO:7; and the scFv variable light domain comprises SEQ ID NO: 8.

14. The method of any one of claims 8-13, wherein the scFv binding domain which binds CD3 comprises an scFv linker.

15. The method of any one of claims 9-15, wherein the first Fc domain comprises amino acid substitutions E233P, L235V, G236A, S267K, R292C, N297G, V302C, E357Q, and S364K; and the second Fc domain comprises amino acid substitutions N208D, E233P, L235V, G236A, S267K, R292C, Q295E, N297G, V302C, L368D, K370S, N384D, Q418E, and N421 D.

16. The method of any one of claims 9-15, wherein the first Fc domain and the second Fc domain each comprise a deletion at position 234.

17. The method of any one of claims 1-16, wherein the anti-STEAP1 antigen binding protein comprises a heavy chain comprising SEQ ID NO: 17 or 23, a heavy chain with inserted CD3 scFv comprising SEQ ID NO: 19 or 26, and two light chains, each comprising SEQ ID NO: 18.

18. The method of any one of claims 1-17, wherein the anti-STEAP1 antigen binding protein is xaluritamig.

19. The method of claim 18, comprising administering xaluritamig to the patient by step dosing.

20. The method of claim 18, comprising administering xaluritamig to the patient by step dosing as follows: administering 0.1 mg of xaluritamig on day 1 , administering 0.3 mg of xaluritamig on day 8 administering 1.0 mg of xaluritamig on day 15, and administering 1 .0 mg of xaluritamig on day 22.21 . The method of claim 10 or claim 20, further comprising administering xaluritamig to the patient once per two weeks after administration of the step dosing.32512 / 7053822. The method of claim 19 or claim 20, further comprising administering xaluritamig to the patient once per three weeks or once per four weeks after administration of the step dosing.

23. The method of claim 21 , comprising administering 1 .0 mg xaluritamig to the patient once per two weeks after administration of the step dosing.

24. A method of treating a patient having prostate cancer, comprising administering to a patient having (a) high-risk biochemical recurrence of nonmetastatic castrationsensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormonesensitive prostate cancer a pharmaceutical composition comprising xaluritamig over the course of at least two 28 day cycles, as follows(i) Cycle 1 : administering 0.1 mg of xaluritamig on day 1 , administering 0.3 mg of xaluritamig on day 8 administering 1.0 mg of xaluritamig on day 15, and administeringl .0 mg of xaluritamig is administered on day 22, followed by one or more of(ii) Cycle 2: administering 1 .0 mg of xaluritamig once per two weeks.

25. The method of claim 24, wherein patient has localized prostate cancer, and cycle 2 is performed once.

26. The method of claim 24, wherein patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, and cycle 2 is performed five times.

27. The method of any one of claims 1-26, comprising administering the anti-STEAP1 antigen binding protein, without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.

28. The method of any one of claims 1-27, wherein the patient has high-risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer.

29. The method of any one of claims 1-27, wherein the patient has localized prostate cancer.

30. The method of any one of claims 1-27, wherein the patient has metastatic hormonesensitive prostate cancer.31 . Use of an anti-STEAP1 antigen binding protein in the manufacture of a medicament for treating prostate cancer, wherein the medicament is formulated for administration at a dose of about 0.001 mg to about 2.0 mg, wherein the prostate cancer is (a) high- risk biochemical recurrence of nonmetastatic castration-sensitive prostate cancer, (b) localized prostate cancer, or (c) metastatic hormone-sensitive prostate cancer, and32512 / 70538 wherein the anti-STEAP1 antigen binding protein comprises (i) a STEAP1 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 9, HCDR2 comprising SEQ ID NO: 10, and HCDR3 comprising SEQ ID NO: 11 ; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 12, LCDR2 comprising SEQ ID NO: 13, and LCDR3 comprising SEQ ID NO: 14, and (ii) a CD3 binding domain comprising a variable heavy domain comprising HCDR1 comprising SEQ ID NO: 1 , HCDR2 comprising SEQ ID NO: 2, and HCDR3 comprising SEQ ID NO: 3; and a variable light domain comprising LCDR1 comprising SEQ ID NO: 4, LCDR2 comprising SEQ ID NO:5, and LCDR3 comprising SEQ ID NO: 6.

32. The use of claim 31 , wherein the dose is about 0.1 mg.

33. The use of claim 31 , wherein the dose is about 0.3 mg.

34. The use of claim 31 , wherein the dose is about 0.75 mg.

35. The use of claim 31 , wherein the dose is about 1 mg.

36. The use of any one of claims 31-35, wherein the dose is administered once per one week.

37. The use of any one of claims 31-35, wherein the dose is administered once per two weeks.

38. The use of any one of claims 31-35, wherein the anti-STEAP1 antigen binding protein is administered, without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.

39. The use of any one of claims 31-35, wherein the anti-STEAP1 antigen binding protein (i) comprises two STEAP1 binding domains that are each Fab binding domains and (ii) the CD3 binding domain is an scFv binding domain.

40. The use of any one of claims 31-39, wherein the anti-STEAP1 antigen binding protein comprises a first Fc domain and a second Fc domain.

41. The use of any one of claims 31-40, wherein the anti-STEAP1 antigen binding protein is an XmAb® 2+1 molecule.

42. The use of any one of claims 31 -41 , wherein each Fab variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15 or 20; each Fab variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 16; and the scFv variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8.

43. The use of any one of claims 31-42, wherein each Fab variable heavy domain comprises SEQ ID NO: 15 or 20; each Fab variable light domain comprises SEQ ID NO: 16; the scFv variable heavy domain comprises SEQ ID NO:7; and the scFv variable light domain comprises SEQ ID NO: 8.32512 / 7053844. The use of any one of claims 31-43, wherein the scFv binding domain which binds CD3 comprises an scFv linker.

45. The use of any one of claims 31-44, wherein the first Fc domain comprises amino acid substitutions E233P, L235V, G236A, S267K, R292C, N297G, V302C, E357Q, and S364K; and the second Fc domain comprises amino acid substitutions N208D, E233P, L235V, G236A, S267K, R292C, Q295E, N297G, V302C, L368D, K370S, N384D, Q418E, and N421 D.

46. The use of any one of claims 31-45, wherein the first Fc domain and the second Fc domain each comprise a deletion at position 234.

47. The use of any one of claims 31-46, wherein the anti-STEAP1 antigen binding protein comprises a heavy chain comprising SEQ ID NO: 17 or 23, a heavy chain with inserted CD3 scFv comprising SEQ ID NO: 19 or 26, and two light chains, each comprising SEQ ID NO: 18.

48. The use of any one of claims 31-47, wherein the anti-STEAP1 antigen binding protein is xaluritamig.

49. The use of claim 48, wherein the xaluritamig is administered by step dosing.

50. The use of claim 49, wherein xaluritamig is administered to the patient by step dosing as follows:0.1 mg of xaluritamig is administered on day 1 , 0.3 mg of xaluritamig is administered on day 8 1 .0 mg of xaluritamig is administered on day 15, and 1 .0 mg of xaluritamig is administered on day 22.51 . The use of claim 48 or claim 49, further comprising administering xaluritamig to the patient once per two weeks after administration of the step dosing.

52. The use of claim 48 or claim 49, further comprising administering xaluritamig to the patient once per three weeks or once per four weeks after administration of the step dosing.

53. The use of claim 52, comprising administering 1 .0 mg xaluritamig to the patient once per two weeks after administration of the step dosing.

54. The use of any one of claims 31-53, wherein the patient has biochemical recurrence of nonmetastatic castration-sensitive prostate cancer.

55. The use of any one of claims 31-53, wherein the patient has localized prostate cancer.

56. The use of any one of claims 31 -53, wherein the patient has metastatic hormonesensitive prostate cancer.32512 / 7053857. An anti-STEAP1 antigen binding protein for use in the treatment of prostate cancer, wherein the anti-STEAP1 antigen binding protein is formulated for administration at a dose of about 0.1 mg to about 2.0 mg.

58. The anti-STEAP1 antigen binding protein of claim 57, wherein the dose is about 0.1 mg.

59. The anti-STEAP1 antigen binding protein of claim 57, wherein the dose is about 0.3 mg.

60. The anti-STEAP1 antigen binding protein of claim 57, wherein the dose is about 0.75 mg.61 . The anti-STEAP1 antigen binding protein of claim 57, wherein the dose is about 1 mg.

62. The anti-STEAP1 antigen binding protein of any one of claims 57-61 , wherein the dose is administered once per one week.

63. The anti-STEAP1 antigen binding protein of any one of claims 57-61 , wherein the dose is administered once per two weeks.

64. The anti-STEAP1 antigen binding protein of any one of claims 57-61 , wherein the anti-STEAP1 antigen binding protein is administered, without prior administration of another anti-cancer therapy, and before the patient has a radical prostatectomy or radiotherapy.

65. The anti-STEAP1 antigen binding protein of any one of claims 57-61 , wherein the anti-STEAP1 antigen binding protein (i) comprises two STEAP1 binding domains that are each Fab binding domains and (ii) the CD3 binding domain is an scFv binding domain.

66. The anti-STEAP1 antigen binding protein of any one of claims 57-65, wherein the anti-STEAP1 antigen binding protein comprises a first Fc domain and a second Fc domain.

67. The anti-STEAP1 antigen binding protein of any one of claims 57-66, wherein the anti-STEAP1 antigen binding protein is an XmAb® 2+1 molecule.

68. The anti-STEAP1 antigen binding protein of any one of claims 57-67, wherein each Fab variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 15 or 20; each Fab variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 16; and the scFv variable heavy domain comprises an amino acid sequence at least 90% identical to SEQ ID NO:7; and the scFv variable light domain comprises an amino acid sequence at least 90% identical to SEQ ID NO: 8.

69. The anti-STEAP1 antigen binding protein of any one of claims 57-68, wherein each Fab variable heavy domain comprises SEQ ID NO: 15 or 20; each Fab variable light32512 / 70538 domain comprises SEQ ID NO: 16; the scFv variable heavy domain comprises SEQ ID NO:7; and the scFv variable light domain comprises SEQ ID NO: 8.

70. The anti-STEAP1 antigen binding protein of any one of claims 57-69, wherein the scFv binding domain which binds CD3 comprises an scFv linker.71 . The anti-STEAP1 antigen binding protein of any one of claims 57-70, wherein the first Fc domain comprises amino acid substitutions E233P, L261 V, G236A, S267K, R292C, N297G, V302C, E617Q, and S364K; and the second Fc domain comprises amino acid substitutions N208D, E233P, L261V, G236A, S267K, R292C, Q295E, N297G, V302C, L368D, K370S, N384D, Q418E, and N421 D.

72. The anti-STEAP1 antigen binding protein of any one of claims 57-71 , wherein the first Fc domain and the second Fc domain each comprise a deletion at position 234.

73. The anti-STEAP1 antigen binding protein of any one of claims 57-72, wherein the anti-STEAP1 antigen binding protein comprises a heavy chain comprising SEQ ID NO: 17 or 23, a heavy chain with inserted CD3 scFv comprising SEQ ID NO: 19 or 26, and two light chains, each comprising SEQ ID NO: 18.

74. The anti-STEAP1 antigen binding protein of any one of claims 57-73, wherein the anti-STEAP1 antigen binding protein is xaluritamig.

75. The anti-STEAP1 antigen binding protein of claim 74, wherein xaluritamig is administered by step dosing.

76. The anti-STEAP1 antigen binding protein of claim 75, wherein xaluritamig is administered to the patient by step dosing as follows:0.1 mg of xaluritamig is administered on day 1 , 0.3 mg of xaluritamig is administered on day 8 1 .0 mg of xaluritamig is administered on day 15, and 1 .0 mg of xaluritamig is administered on day 22.

77. The anti-STEAP1 antigen binding protein of claim 75 or claim 76, further comprising administering xaluritamig to the patient once per two weeks after administration of the step dosing.

78. The anti-STEAP1 antigen binding protein of claim 75 or claim 76, further comprising administering xaluritamig to the patient once per three weeks or once per four weeks after administration of the step dosing.

79. The anti-STEAP1 antigen binding protein of claim 78, comprising administering 1 .0 mg xaluritamig to the patient once per two weeks after administration of the step dosing.

80. The anti-STEAP1 antigen binding protein of any one of claims 57-79, wherein the patient has biochemical recurrence of nonmetastatic castration-sensitive prostate cancer.32512 / 7053881 . The anti-STEAP1 antigen binding protein of any one of claims 57-79, wherein the patient has localized prostate cancer.

82. The anti-STEAP1 antigen binding protein of any one of claims 57-79, wherein the patient has metastatic hormone-sensitive prostate cancer.

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