Combination therapies for the treatment of cancer
Patent Information
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- HOOLA THERAPEUTICS INC
- Filing Date
- 2026-04-07
- Publication Date
- 2026-07-17
Smart Images
Figure 00000000_0000_ABST
Abstract
Description
CN Title: Combination Therapy for Treating Cancer CN Abstract: This article provides methods and compositions for treating cancer, including the combined use of ROR1 antagonists and checkpoint inhibitor antagonists. 1 Abstract
Claims
CLAIMSWhat is claimed is:
1. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a tyrosine kinase-like orphan receptor 1 (R0R1) antagonist and a therapeutically effective amount of an immune checkpoint inhibitor to the subject.
2. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-1 inhibitor, or a PD-Ll inhibitor.
3. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is a small molecule drug.
4. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises an antibody, a peptide, or a protein.
5. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-1 inhibitor.
6. The method of the claim 5, wherein the PD-1 inhibitor is a PD-1 inhibitor antibody.
7. The method of claim 6, wherein the PD-1 inhibitor antibody comprises nivolumab, pembrolizumab, cemiplimab, dorstarlimab, or combinations thereof.
8. The method of claim 7, wherein the PD-1 inhibitor antibody comprises pembrolizumab.
9. The method of claim 6, wherein the PD-1 inhibitor antibody comprises JTX-4014, spartalizumab (PDR001), camrelizumab (SHR1210), sintilmab (IBI308), tislelizumab (BGB- A317), toripalimab (JS 001), Retifanlimab (INCMGA00012) (MGA012), AMP-224, AMP- 514, or combinations thereof.
10. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-Ll inhibitor.
11. The method of claim 10, wherein the PD-L1 inhibitor is a PD-L1 inhibitor antibody.
12. The method of claim 11, wherein the PD -LI inhibitor antibody comprises atezolizumab, avelumab, durvalumab, or combinations thereof.
13. The method of claim 11, wherein the PD-L1 inhibitor antibody comprises Envafolimab (KN035), Cosibelimab (CK-301), AUNP12, CA-170, BMS-986189, or combinations thereof.
14. The method of any one of the preceding claims, wherein the R0R1 antagonist is an antibody or a small molecule.
15. The method of any one of the preceding claims, wherein the antibody comprises a Fab, F(ab’)2, Fv, or an scFv.
16. The method of any one of the preceding claims, wherein the R0R1 antagonist is an anti- R0R1 antibody.
17. The method of any one of the preceding claims, wherein the antibody is zilovertamab.
18. The method of any one of the preceding claims, wherein the antibody binds to an R0R1 amino acid sequence as set forth in SEQ ID NO 30 or SEQ ID NO: 31.
19. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered in a combined synergistic amount.
20. The method of any one of the preceding claims, further comprising reducing the growth of a tumor.
21. The method of any one of the preceding claims, wherein the method reduces the growth of a tumor by about 20% or more.
22. The method of any one of the preceding claims, wherein the method reduces the growth of a tumor by from about 25% to about 45% when compared to administration of the immune checkpoint inhibitor and the ROR1 antagonist separately.
23. The method of any one of the preceding claims, further comprising reducing the mass or volume of a tumor.
24. The method of any one of the preceding claims, wherein the antibody comprises a humanized heavy chain variable region and a humanized light chain variable region, whereinsaid humanized heavy chain variable region comprises the sequences set forth in SEQ ID NO. 1, SEQ ID NO. 2, and SEQ ID NO. 3; and wherein said humanized light chain variable region comprises the sequences set forth in SEQ ID NO. 4, SEQ ID NO. 5, and SEQ ID NO.6.
25. The method of any one of the preceding claims, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence at least about 85%, 90%, 95%, 97%, 98%, 99%, or 100 identical to that set forth in SEQ ID NO: 7; and wherein the light chain variable region comprises an amino acid sequence at least about 85%, 90%, 95%, 97%, 98%, 99%, or 100 identical to that set forth in SEQ ID NO: 8.
26. The method of any one of the preceding claims, wherein an immune cell infiltrate of the cancer expresses PD-1.
27. The method of any one of the preceding claims, wherein the cancer expresses PD-L1.
28. The method of any one of the preceding claims, wherein the cancer over expresses PD- Ll.
29. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered substantially simultaneously.
30. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered separately.
31. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered sequentially.
32. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are co-formulated for administration by a single formulation.
33. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered in separate compositions.
34. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are admixed prior to administration.
35. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered by intravenous infusion.
36. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered once every t wo-weeks.
37. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered once every three-weeks.
38. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered once every four-weeks.
39. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage from about 200 milligrams to about 2000 milligrams.
40. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage from about 200 milligrams to about 800 milligrams.
41. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage from about 300 milligrams to about 600 milligrams.
42. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage of about 300 milligrams.
43. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage of about 600 milligrams.
44. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 200 mg every six weeks; 300 mg every six weeks, or 400 mg every six weeks.
45. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 100 mg every three weeks; or 300 mg every six weeks.
46. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 2 mg / kg, or 1 mg / kg every 3 weeks.
47. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 50 mg every three weeks; or 100 mg every six weeks.
48. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of about 50 mg to about 400 mg every three weeks.
49. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in a 25 mg / mL solution.
50. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered by injection, or intravenous infusion.
51. The method of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage of about 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.5, 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 mg / kg.
52. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage from about 200 milligrams to about 2000 milligrams.
53. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage from about 200 milligrams to about 800 milligrams.
54. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage from about 300 milligrams to about 600 milligrams.
55. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage of about 300 milligrams.
56. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage of about 600 milligrams.
57. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage of about 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.5, 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 mg / kg.
58. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered in a 25 mg / mL solution.
59. The method of any one of the preceding claims, wherein the R0R1 antagonist is administered once every two-weeks.
60. The method of any one of the preceding claims, wherein the ROR1 antagonist is administered once every three-weeks.
61. The method of any one of the preceding claims, wherein the ROR1 antagonist is administered once every four-weeks.
62. The method of any one of the preceding claims, wherein the subject is a mammal.
63. The method of any one of the preceding claims, wherein the subject is a human.
64. The method of any one of the preceding claims, wherein the cancer is lymphoma, leukemia, myeloma, renal cell carcinoma, colon cancer, colorectal cancer, breast cancer, epithelial squamous cell cancer, melanoma, stomach cancer, brain cancer, lung cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, prostate cancer, testicular cancer, thyroid cancer, head and neck cancer, uterine cancer, adenocarcinoma, sarcoma, or adrenal cancer.
65. The method of any one of the preceding claims, wherein the cancer is chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, mantle cell lymphoma (MCL), marginal cell B-Cell lymphoma, Burkitt's Lymphoma, myeloma, AML, B-ALL, T-ALL, or B cell leukemia.
66. A pharmaceutical composition comprising a therapeutically effective amount of a tyrosine kinase-like orphan receptor 1 (ROR1) antagonist and a therapeutically effective amount of an immune checkpoint inhibitor.
67. The pharmaceutical composition of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-1 inhibitor, or a PD-Ll inhibitor.
68. The pharmaceutical composition of any one of the preceding claims, wherein the immune checkpoint inhibitor is a small molecule drug.
69. The pharmaceutical composition of any one of the preceding claims, wherein the immune checkpoint inhibitor is an antibody.
70. The pharmaceutical composition of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-1 inhibitor.
71. The pharmaceutical composition of claim 70, wherein the PD-1 inhibitor is a PD-1 inhibitor antibody.
72. The pharmaceutical composition of claim 71, wherein the PD-1 inhibitor antibody comprises nivolumab, pembrolizumab, cemiplimab, dorstarlimab, or combinations thereof.
73. The pharmaceutical composition of claim 72, wherein the PD-1 inhibitor antibody comprises pembrolizumab.
74. The pharmaceutical composition of claim 71, wherein the PD-1 inhibitor antibody comprises JTX-4014, spartalizumab (PDR001), camrelizumab (SHR1210), sintilmab (IBI308), tislelizumab (BGB-A317), toripalimab (JS 001), RETIFANLIMAB (INCMGA00012) (MGA012), AMP-224, AMP-514, or combinations thereof.
75. The pharmaceutical composition of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-Ll inhibitor.
76. The pharmaceutical composition of claim 75, wherein the PD -LI inhibitor is a PD-Ll inhibitor antibody.
77. The pharmaceutical composition of claim 76, wherein the PD -LI inhibitor antibody comprises atezolizumab, avelumab, durvalumab, or combinations thereof.
78. The pharmaceutical composition of claim 75, wherein the PD -LI inhibitor antibody comprises Envafolimab (KN035), Cosibelimab (CK-301), AUNP12, CA-170, BMS-986189, or combinations thereof.
79. The pharmaceutical composition of any one of the preceding claims, wherein the ROR1 antagonist is an antibody or a small molecule.
80. The pharmaceutical composition of any one of the preceding claims, wherein the antibody comprises a Fab, F(ab’)2, Fv, or an scFv.
81. The pharmaceutical composition of any one of the preceding claims, wherein the ROR1 antagonist is an anti-RORl antibody.
82. The pharmaceutical composition of any one of the preceding claims, wherein the antibody is zilovertamab.
83. The pharmaceutical composition of any one of the preceding claims, wherein the immune checkpoint inhibitor and the R0R1 antagonist are administered in a combined synergistic amount.
84. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition reduces the growth of a tumor when administered to a subject.
85. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition reduces the growth of a tumor by about 20% or more when administered to a subject.
86. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition reduces the growth of a tumor by from about 25% to about 45% when administered to a subject when compared to administration of the immune checkpoint inhibitor and the ROR1 antagonist separately.
87. The pharmaceutical composition of any one of the preceding claims, wherein the pharmaceutical composition reduces the mass or volume of a tumor when administered to a subject.
88. The pharmaceutical composition of any one of the preceding claims, wherein the antibody comprises a humanized heavy chain variable region and a humanized light chain variable region, wherein said humanized heavy chain variable region comprises the sequences set forth in SEQ ID NO. 1, SEQ ID NO. 2, and SEQ ID NO. 3; and wherein said humanized light chain variable region comprises the sequences set forth in SEQ ID NO . 4, SEQ ID NO. 5, and SEQ ID NO. 6.
89. The pharmaceutical composition of any one of the preceding claims, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence at least about 85%, 90%, 95%, 97%, 98%, 99%, or 100 identical to that set forth in SEQ ID NO: 7; and wherein thelight chain variable region comprises an amino acid sequence at least about 85%, 90%, 95%, 97%, 98%, 99%, or 100 identical to that set forth in SEQ ID NO: 8.
90. The pharmaceutical composition of any one of the preceding claims, wherein the immune checkpoint inhibitor is comprised in an amount of about 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.5, 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12,12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 mg / kg.
91. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 200 milligrams to about 2000 milligrams.
92. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 200 milligrams to about 800 milligrams.
93. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 300 milligrams to about 600 milligrams.
94. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 300 milligrams to about 600 milligrams.
95. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 300 milligrams.
96. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 600 milligrams.
97. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.5, 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11,11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 mg / kg.
98. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist in an amount of about 10, 15, 20, 25, or 30 mg / mL.
99. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the immune checkpoint inhibitor in an amount of about 200 milligrams to about 800 milligrams.
100. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the immune checkpoint inhibitor in an amount of about 300 milligrams to about 600 milligrams.
101. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the immune checkpoint inhibitor in an amount of about 300 milligrams to about 600 milligrams.
102. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the immune checkpoint inhibitor in an amount of about 300 milligrams.
103. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the immune checkpoint inhibitor in an amount of about 600 milligrams.
104. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the immune checkpoint inhibitor in an amount of about 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.5, 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 mg / kg.
105. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the immune checkpoint inhibitor in an amount of about 10, 15, 20, 25, or 30 mg / mL.
106. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist and the immune checkpoint inhibitor in a combined synergistic amount.
107. The pharmaceutical composition of any one of the preceding claims, wherein the composition comprises the ROR1 antagonist and the immune checkpoint inhibitor in a combined synergistic amount effective to treat a cancer in a subject.
108. The pharmaceutical composition of claim 107, wherein the cancer comprises a mutated PD-L1 gene.
109. The pharmaceutical composition of claim 107, wherein the cancer expresses PD-L1.
110. The pharmaceutical composition of claim 107, wherein the cancer over expresses PD- Ll.
111. The pharmaceutical composition of claim 107, wherein the cancer is lymphoma, leukemia, myeloma, renal cell carcinoma, colon cancer, colorectal cancer, breast cancer, epithelial squamous cell cancer, melanoma, stomach cancer, brain cancer, lung cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, prostate cancer, testicular cancer, thyroid cancer, head and neck cancer, uterine cancer, adenocarcinoma, sarcoma, or adrenal cancer.
112. The pharmaceutical composition of claim 107, wherein the cancer is chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, mantle cell lymphoma (MCL), marginal cell B-Cell lymphoma, Burkitt's Lymphoma, myeloma, AML, B-ALL, T-ALL, or B cell leukemia.
113. The pharmaceutical composition of any one of the preceding claims, wherein the ROR1 antagonist and the checkpoint inhibitor are in separate compositions.
114. Use of the pharmaceutical composition of any one of claims 66-113 in a method of treating a cancer in a subject in need thereof, comprising administering the pharmaceutical composition to the subject.
115. Use of a therapeutically effective amount of a tyrosine kinase-like orphan receptor 1 (ROR1) antagonist and a therapeutically effective amount of an immune checkpoint inhibitor in a method of treating a cancer in a subject in need thereof, comprising administering the pharmaceutical composition to the subject.
116. The use of a therapeutically effective amount of a tyrosine kinase-like orphan receptor 1 (R0R1) antagonist and a therapeutically effective amount of an immune checkpoint inhibitor for the manufacture of a medicament for treating cancer in a subject in need thereof.
117. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-1 inhibitor, or a PD-Ll inhibitor118. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is a small molecule drug.
119. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises an antibody, a peptide, or a protein.
120. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-1 inhibitor.
121. The use of the claim 120, wherein the PD-1 inhibitor is a PD-1 inhibitor antibody.
122. The use of claim 121, wherein the PD-1 inhibitor antibody comprises nivolumab, pembrolizumab, cemiplimab, dorstarlimab, or combinations thereof.
123. The use of claim 122, wherein the PD-1 inhibitor antibody comprises pembrolizumab.
124. The use of claim 121, wherein the PD-1 inhibitor antibody comprises JTX-4014, spartalizumab (PDR001), camrelizumab (SHR1210), sintilmab (IBI308), tislelizumab (BGB- A317), toripalimab (JS 001), Retifanlimab (INCMGA00012) (MGA012), AMP -224, AMP- 514, or combinations thereof.
125. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor comprises a PD-Ll inhibitor.
126. The use of claim 125, wherein the PD-L1 inhibitor is a PD-L1 inhibitor antibody.
127. The use of claim 126, wherein the PD-L1 inhibitor antibody comprises atezolizumab, avelumab, durvalumab, or combinations thereof.
128. The use of claim 126, wherein the PD-L1 inhibitor antibody comprises Envafolimab (KN035), Cosibelimab (CK-301), AUNP12, CA-170, BMS-986189, or combinations thereof.
129. The use of any one of the preceding claims, wherein the ROR1 antagonist is an antibody or a small molecule.
130. The use of any one of the preceding claims, wherein the antibody comprises a Fab, F(ab’)2, Fv, or an scFv.
131. The use of any one of the preceding claims, wherein the R0R1 antagonist is an anti- ROR1 antibody.
132. The use of any one of the preceding claims, wherein the antibody is zilovertamab.
133. The use of any one of the preceding claims, wherein the antibody binds to an ROR1 amino acid sequence as set forth in SEQ ID NO 30 or SEQ ID NO: 31.
134. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered in a combined synergistic amount.
135. The use of any one of the preceding claims, further comprising reducing the growth of a tumor.
136. The use of any one of the preceding claims, wherein the use reduces the growth of a tumor by about 20% or more.
137. The use of any one of the preceding claims, wherein the use reduces the growth of a tumor by from about 25% to about 45% when compared to administration of the immune checkpoint inhibitor and the ROR1 antagonist separately.
138. The use of any one of the preceding claims, further comprising reducing the mass or volume of a tumor.
139. The use of any one of the preceding claims, wherein the antibody comprises a humanized heavy chain variable region and a humanized light chain variable region, wherein said humanized heavy chain variable region comprises the sequences set forth in SEQ ID NO. 1, SEQ ID NO. 2, and SEQ ID NO. 3; and wherein said humanized light chain variable region comprises the sequences set forth in SEQ ID NO. 4, SEQ ID NO. 5, and SEQ ID NO. 6.
140. The use of any one of the preceding claims, wherein the antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises an amino acid sequence at least about 85%, 90%, 95%, 97%, 98%, 99%, or 100 identical to that set forth in SEQ ID NO: 7; and wherein the light chain variable region comprises an amino acid sequence at least about 85%, 90%, 95%, 97%, 98%, 99%, or 100 identical to that set forth in SEQ ID NO: 8.
141. The use of any one of the preceding claims, wherein an immune cell infiltrate of the cancer expresses PD-1.
142. The use of any one of the preceding claims, wherein the cancer expresses PD-L1.
143. The use of any one of the preceding claims, wherein the cancer over expresses PD-L1.
144. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered substantially simultaneously.
145. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered separately.
146. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered sequentially.
147. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are co-formulated for administration by a single formulation.
148. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are administered in separate compositions.
149. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor and the ROR1 antagonist are admixed prior to administration.
150. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered by intravenous infusion.
151. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered once every t wo-weeks.
152. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered once every three-weeks.
153. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered once every four-weeks.
154. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage from about 200 milligrams to about 2000 milligrams.
155. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage from about 200 milligrams to about 800 milligrams.
156. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage from about 300 milligrams to about 600 milligrams.
157. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage of about 300 milligrams.
158. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage of about 600 milligrams.
159. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 200 mg every six weeks; 300 mg every six weeks, or 400 mg every six weeks.
160. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 100 mg every three weeks; or 300 mg every six weeks.
161. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 2 mg / kg, or 1 mg / kg every 3 weeks.
162. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of 50 mg every three weeks; or 100 mg every six weeks.
163. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in an amount of about 50 mg to about 400 mg every three weeks.
164. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered in a 25 mg / mL solution.
165. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered by injection, or intravenous infusion.
166. The use of any one of the preceding claims, wherein the immune checkpoint inhibitor is administered at a dosage of about 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.5, 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 mg / kg.
167. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage from about 200 milligrams to about 2000 milligrams.
168. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage from about 200 milligrams to about 800 milligrams.
169. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage from about 300 milligrams to about 600 milligrams.
170. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage of about 300 milligrams.
171. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage of about 600 milligrams.
172. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered at a dosage of about 0.50, 0.75, 1.00, 1.25, 1.50, 1.75, 2.0, 2.25, 2.50, 2.75, 3.00, 3.5, 4, 4.5, 5, 5.5, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, or 20 mg / kg.
173. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered in a 25 mg / mL solution.
174. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered once every two-weeks.
175. The use of any one of the preceding claims, wherein the ROR1 antagonist is administered once every three-weeks.
176. The use of any one of the preceding claims, wherein the R0R1 antagonist is administered once every four-weeks.
177. The use of any one of the preceding claims, wherein the subject is a mammal.
178. The use of any one of the preceding claims, wherein the subject is a human.
179. The use of any one of the preceding claims, wherein the cancer is lymphoma, leukemia, myeloma, renal cell carcinoma, colon cancer, colorectal cancer, breast cancer, epithelial squamous cell cancer, melanoma, stomach cancer, brain cancer, lung cancer, pancreatic cancer, cervical cancer, ovarian cancer, liver cancer, bladder cancer, prostate cancer, testicular cancer, thyroid cancer, head and neck cancer, uterine cancer, adenocarcinoma, sarcoma, or adrenal cancer.
180. The use of any one of the preceding claims, wherein the cancer is chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, mantle cell lymphoma (MCL), marginal cell B-Cell lymphoma, Burkitt's Lymphoma, myeloma, AML, B-ALL, T-ALL, or B cell leukemia.