Biomarkers for predicting cancer treatment efficacy

Abstract

Provided herein are biomarkers useful for identifying patients suitable for therapy comprising immune checkpoint inhibitors, and methods of using these biomarkers. In particular, the present disclosure provides techniques for treating and predicting cancer in a patient using biomarker expression levels in a biological sample obtained from the patient, as well as techniques for determining the likelihood that a patient will respond to therapy comprising an immune checkpoint inhibitor.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480034905.2 (22) Application Date 2024.05.31 (30) Priority Data 63 / 470,660 2023.06.02 US 63 / 539,295 2023.09.19 US 63 / 649,808 2024.05.20 US (85) PCT International Application Entering National Phase Date 2025.11.25 (86) PCT International Application Application Data PCT / US2024 / 032049 2024.05.31 (87) PCT International Application Publication Data WO2024 / 249894 EN 2024.12.05 (71) Applicant: Ekus Biosciences, Inc. Address: California, USA (72) Inventors: D.M. Direnzo, A.G. Dupag, K.S. Gautier, J.C. Jain, S. Jaffrey, O. Kabala, A.J.M. Kaplan, D. Piovinsang, R. Ray, L.C. Seitz, M.J. Walters, J.M. Inling (74) Patent Agency: Beijing Liushen Law Firm, 11105 Patent Attorney: Qin Jian (51) Int.Cl. G01N 33 / 68 (2006.01) G01N 33 / 575 (2026.01) A61K 39 / 395 (2006.01) A61P 35 / 00 (2006.01) (54) Title of Invention: Biomarkers for Predicting the Efficacy of Cancer Treatment (57) Abstract This document provides biomarkers that can be used to identify patients suitable for therapies containing immune checkpoint inhibitors, and methods for using these biomarkers. Specifically, this disclosure provides techniques for treating and predicting a patient's cancer using the expression levels of biomarkers in biological samples obtained from the patient, and techniques for determining the likelihood that a patient will respond to a therapy containing an immune checkpoint inhibitor. Claims 7 pages Description 79 pages Drawings 51 pages CN 121285743 A 2026.01.06 CN 1 21 28 57 43 A

Claims

1. Use of a biomarker for identifying a patient suitable for treatment with a combination therapy comprising an anti-TIGIT antibody and an anti-PD-(L)1 antibody, wherein the patient has a cancer and is identified as suitable for treatment with the combination therapy when a sample obtained from the patient contains a biomarker comprising a CD155 expression level greater than or equal to a CD155 reference level, and wherein optionally the biomarker further comprises: (a) a PD-L1 expression level greater than or equal to a PD-L1 reference level; (b) a CD226 expression level greater than or equal to a CD226 reference level; (c) an adenosine pathway biomarker expression level lower than an adenosine pathway biomarker reference level; (d) a CD73 expression level lower than a CD73 reference level; or (e) any combination of (a), (b), (c), and (d).

2. The use of claim 1, wherein the anti-TIGIT antibody is (i) an Fc silent anti-TIGIT antibody, or (ii) domvanalimumab.

3. The use of claim 1 or 2, wherein the combination therapy further comprises chemotherapy.

4. The use of any one of claims 1-3, wherein the cancer is (i) Stage I, II, or III, optionally wherein the cancer is resectable, or (ii) locally advanced or metastatic.

5. The use of any one of claims 1-4, wherein the cancer is a solid tumor.

6. The use of claim 5, wherein the cancer is selected from the group consisting of a gastrointestinal cancer, a genitourinary cancer, a gynecological cancer, a head and neck cancer, and a lung cancer.

7. A method for treating a cancer in a patient, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of an anti-TIGIT antibody and a therapeutically effective amount of an anti-PD-(L)1 antibody when a sample obtained from the patient contains a biomarker comprising a CD155 expression level greater than or equal to a CD155 reference level, and wherein optionally the biomarker further comprises: (a) a PD-L1 expression level greater than or equal to a PD-L1 reference level; (b) a CD226 expression level greater than or equal to a CD226 reference level; (c) an adenosine pathway biomarker expression level lower than an adenosine pathway biomarker reference level; (d) a CD73 expression level lower than a CD73 reference level; or (e) any combination of (a), (b), (c), and (d).

8. The method of claim 7, wherein the anti-TIGIT antibody is (i) an Fc silent anti-TIGIT antibody, or (ii) domvanalimumab.

9. The method of claim 7 or 8, wherein the combination therapy further comprises chemotherapy.

10. The method of any one of claims 7-9, wherein the cancer is (i) Stage I, II, or III, optionally wherein the cancer is resectable, or (ii) locally advanced or metastatic.

11. The method of any one of claims 7-10, wherein the cancer is a solid tumor.

12. The method of claim 11, wherein the cancer is selected from the group consisting of a gastrointestinal cancer, a genitourinary cancer, a gynecological cancer, a head and neck cancer, and a lung cancer.

13. A method for identifying a patient having a cancer that is suitable for treatment with a combination therapy comprising a therapeutically effective amount of an anti-TIGIT antibody and a therapeutically effective amount of an anti-PD-(L)1 antibody, the method comprising: (a) measuring the level of CD155 and optionally one or more of PD-L1, CD226, an adenosine pathway biomarker, and CD73 in a sample obtained from the patient; (b) comparing the level measured in (a) to a corresponding reference level; and (c) identifying the patient as suitable for treatment with the therapy when the measured CD155 level is greater than or equal to the CD155 reference level, and optionally the measured PD-L1 level is greater than or equal to the PD-L1 reference level.

14. The method of claim 13, wherein the anti-TIGIT antibody is (i) an Fc silent anti-TIGIT antibody, or (ii) domvanalimumab.

15. The method of claim 13 or 14, wherein the combination therapy further comprises chemotherapy.

16. The method of any one of claims 13-15, wherein the cancer is Stage I, II, or III, optionally wherein the cancer is resectable, or (ii) locally advanced or metastatic.

17. The method of any one of claims 13-16, wherein cancer is a solid tumor.

18. The method of claim 17, wherein the cancer is selected from the group consisting of a gastrointestinal cancer, a genitourinary cancer, a gynecological cancer, a head and neck cancer, and a lung cancer.

19. A method for treating a patient, the method comprising: (a) measuring the level of PD-L1, CD155, and optionally one or more of a biomarker that is (i) a CD226 expression level that is greater than or equal to a CD226 reference level; (ii) an adenosine pathway biomarker expression level that is lower than an adenosine pathway biomarker reference level; (iii) a CD73 expression level that is lower than a CD73 reference level; or (v) any combination of (i), (ii), and (iii) in a sample obtained from the patient; (b) comparing the level of each biomarker measured in (a) to a corresponding reference level; and (c) administering to the patient a combination therapy comprising a therapeutically effective amount of an anti-TIGIT antibody and a therapeutically effective amount of an anti-PD-(L)1 antibody when the measured CD155 level is greater than or equal to the CD155 reference level, and optionally when the measured PD-L1 level is greater than or equal to the PD-L1 reference level when measured.

20. The method of claim 19, wherein the anti-TIGIT antibody is (i) an Fc silent anti-TIGIT antibody, or (ii) domvanalimumab.

21. The method of claim 19 or 20, wherein the combination therapy comprises chemotherapy.

22. The method of any one of claims 19-21, wherein the patient has cancer.

23. The method of any one of claim 22, wherein the patient has a solid tumor.

24. The method of claim 23, wherein the solid tumor is selected from the group consisting of ovarian cancer, endometrial cancer, breast cancer, lung cancer, colon cancer, prostate cancer, cervical cancer, biliary tract cancer, pancreatic cancer, gastric cancer, esophageal cancer, liver cancer, kidney cancer, head and neck cancer, mesothelioma, melanoma, sarcoma, central nervous system (CNS) hemangioblastoma, and brain tumor.

25. The method of claim 22, wherein the patient has a cancer selected from the group consisting of gastrointestinal cancer, genitourinary cancer, gynecological cancer, head and neck cancer, and lung cancer.

26. The use or method of any one of the preceding claims, wherein the sample is a sample comprising tumor cells.

27. The use or method of any one of the preceding claims, wherein the sample is a sample comprising immune cells.

28. The use or method of any one of the preceding claims, wherein the sample is a tumor biopsy.

29. The use or method of any one of the preceding claims, wherein the CD155 expression level is measured by immunohistochemistry (IHC).

30. The use or method of any one of the preceding claims, wherein the reference level is (i) a median expression level derived from samples obtained from a group of patients having the same cancer, or (ii) an amount that is ≤ 30%, ≤ 25%, ≤ 20%, ≤ 15%, ≤ 10%, or ≤ 5% above or below the median expression level.

31. The use or method of claim 29 or 30, wherein the expression level is measured based on IHC staining intensity and / or percentage of stained positive cells.

32. The use or method of claim 31, wherein the stained positive cells are tumor cells.

33. The use or method of claim 31, wherein the stained positive cells are immune cells.

34. The use or method of claim 31, wherein the stained positive cells are cells of the tumor microenvironment and are not immune cells or tumor cells.

35. The use or method of claim 31, wherein the stained positive cells are (i) tumor cells and immune cells, or (i) tumor cells, immune cells, and other cells of the tumor microenvironment.

36. The use or method of any one of claims 31-35, wherein the IHC staining intensity and / or percentage of stained positive cells is determined based on cytoplasmic staining.

37. The use or method of any one of claims 31-35, wherein the IHC staining intensity and / or percentage of stained positive cells is determined based on membrane staining.

38. The use or method of any one of claims 31-35, wherein the IHC staining intensity and / or the percentage of stained positive cells is determined based on cytoplasmic staining and membrane staining.

39. The use or method of any one of claims 1-38, wherein the CD155 expression level is measured as %TC.

40. The use or method of any one of claims 1-38, wherein the CD155 expression level is measured as %IC.

41. The use or method of any one of claims 1-38, wherein the CD155 expression level is measured as H-score.

42. The method of any one of claims 19-41, wherein the sample is PD-L1 high or PD-L1 positive.

43. The method of claim 42, wherein the sample is PD-L1 high when the sample has a PD-L1 positive tumor cell fraction (PD-L1 %TC) of greater than or equal to 50%.

44. The method of claim 42, wherein the sample is PD-L1 high when the sample has a tumor area proportion (TAP) of greater than or equal to 5%.

45. The method of claim 42, wherein the sample is PD-L1 positive when the sample has a PD-L1 positive tumor cell fraction (PD-L1 %TC) of greater than or equal to 1%.

46. The method of claim 42, wherein the sample is PD-L1 positive when the sample has a tumor area proportion (TAP) of greater than or equal to 1%.

47. A method of treating cancer in a patient having a CD155 high tumor, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of a TIGIT antagonist and a therapeutically effective amount of a PD-(L)l antagonist, wherein the CD155 high tumor has a CD155 expression level that is greater than or equal to (i) a median tumor H-score derived from samples obtained from a group of patients known to have the same cancer, or (ii) a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median tumor H-score.

48. The method of claim 47, wherein the CD155 high tumor has a CD155 expression level that is greater than or equal to (i) a median tumor H-score derived from samples obtained from a group of patients known to have the same cancer, or (ii) a value that is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% higher or lower than the median tumor H-score.

49. A method of treating a cancer in a patient having a CD155-high tumor, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of a TIGIT antagonist and a therapeutically effective amount of a PD-(L)l antagonist, wherein the CD155-high tumor has a CD155 expression level greater than or equal to (i) the median 2+ or 3+ % TC derived from samples obtained from a group of patients known to have the same cancer, or (ii) a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median 2+ or 3+ % TC.

50. The method of claim 49, wherein the CD155-high tumor has a CD155 expression level greater than or equal to (i) the median 2+ or 3+ % TC derived from samples obtained from a group of patients known to have the same cancer, or (ii) a value that is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% higher or lower than the median 2+ or 3+ % TC.

51. A method of treating a cancer in a patient having a CD155-high tumor, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of a TIGIT antagonist and a therapeutically effective amount of a PD-(L)l antagonist, wherein the CD155-high tumor has a CD155 tumor H-score of > 95, > 100, > 105, > 110, > 115, > 120, > 125, > 130, > 135, > 140, > 145, > 150, > 155, > 160, > 165, > 170, or > 175.

52. The method of claim 51, wherein the CD155-high tumor has a CD155 tumor H-score of > 110, > 115, > 120, > 125, > 130, > 135, > 140, > 145, > 150, > 155, or > 160.

53. A method of treating a cancer in a patient having a CD155-high tumor, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of a TIGIT antagonist and a therapeutically effective amount of a PD-(L)l antagonist, wherein the CD155-high tumor has a CD155 2+ or 3+ % TC of > 30%, > 35%, > 40%, > 45%, > 50%, > 55%, > 60%, or > 65%.

54. The method of claim 53, wherein the CD155-high tumor has a CD155 2+ or 3+ % TC of > 30%, > 35%, > 40%, > 45%, or > 50%.

55. The method of any one of claims 47-54, wherein the TIGIT antagonist is an anti-TIGIT antibody, the PD-(L) antagonist is an anti-PD-(L)l antibody, or the TIGIT antagonist is an anti-TIGIT antibody and the PD-(L) antagonist is an anti-PD-(L)l antibody.

56. The method of 55, wherein the anti-TIGIT antibody is (i) an Fc silent anti-TIGIT antibody, or (ii) dinaciclib.

57. A method of treating cancer in a patient having a CD155-high tumor, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of an Fc silent anti-TIGIT antibody and a therapeutically effective amount of a PD-(L)l antagonist, wherein the CD155-high tumor has a CD155 expression level greater than or equal to a CD155 reference level.

58. The method of claim 57, wherein the CD155 reference level is (a) a median tumor H-score derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median tumor H-score; or (b) a median 2+ or 3+ % TC derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median 2+ or 3+ % TC; or (c) a tumor H-score of > 95, > 100, > 105, > 110, > 115, > 120, > 125, > 130, > 135, > 140, > 145, > 150, > 155, > 160, > 165, > 170, or > 175; or (d) a 2+ or 3+ % TC of > 30%, > 35%, > 40%, > 45%, > 50%, > 55%, > 60%, or > 65%.

59. The method of claim 57, wherein the CD155 reference level is (a) a median tumor H-score derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% higher or lower than the median tumor H-score; or (b) a median 2+ or 3+ % TC derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% higher or lower than the median 2+ or 3+ % TC; (c) a tumor H-score of > 110, > 115, > 120, > 125, > 130, > 135, > 140, > 145, > 150, > 155, or > 160; or (d) a 2+ or 3+ % TC of > 30%, > 35%, > 40%, > 45%, or > 50%. ​ ​ ​ ​ ​ ​ ​ ​ 60. The method of any one of claims 47-59, wherein the PD-(L) antagonist is an anti-PD-(L)1 antibody, optionally wherein the PD-(L)1 antibody is atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, nivolumab, pembrolizumab, spartalizumab, tislelizumab, tremelimumab, or seviprotumab.

61. The method of any one of claims 47-60, wherein the CD155high tumor is PD-L1 positive, optionally wherein PD-L1 positive is a PD-L1 positive tumor cell fraction (PD-L1 % TC) of greater than or equal to 1%, or a PD-L1 tumor area proportion (TAP) of greater than or equal to 1%, or a PD-L1 CPS score of >1.

62. The method of any one of claims 47-60, wherein the PD-L1 expression level in the CD155high tumor is >10% TC.

63. The method of any one of claim 62, wherein the PD-L1 expression level in the CD155high tumor is >10% TC.

64. The method of any one of claim 62, wherein the PD-L1 expression level in the CD155high tumor is >50% TC.

65. The method of any one of claims 47-60, wherein the PD-L1 expression level in the CD155high tumor is >5% TAP or CPS >5.

66. The method of any one of claim 65, wherein the PD-L1 expression level in the CD155high tumor is >10% TAP or CPS >10.

67. A method of treating cancer in a patient having a CD155high tumor, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of an anti-TIGIT antagonist and a therapeutically effective amount of a PD-(L)1 antagonist, wherein the CD155 expression level of the CD155high tumor is greater than or equal to a CD155 reference level, and wherein the PD-L1 expression level in the CD155high tumor is >10% TC, >5% TAP, or >5% CPS.

68. The method of claim 67, wherein the PD-L1 expression level in the CD155high tumor is >10% TAP or CPS >10.

69. The method of claim 67, wherein the PD-L1 expression level in the CD155high tumor is >50% TC.

70. The method of any one of claims 67-69, wherein the CD155 reference level is (a) a median tumor H-score derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median tumor H-score; or (b) a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than a reference value, wherein the reference value is a median tumor H-score derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median tumor H-score. ​ (b) a median 2+ or 3+ % TC derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median 2+ or 3+ % TC; (c) a tumor H-score of > 95, > 100, > 105, > 110, > 115, > 120, > 125, > 130, > 135, > 140, > 145, > 150, > 155, > 160, > 165, > 170, or > 175; or (d) 2+ or 3+ % TC of > 30%, > 35%, > 40%, > 45%, > 50%, > 55%, > 60%, or > 65%.

71. The method of any one of claims 67-69, wherein the CD155 reference level is (a) a median tumor H-score derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% higher or lower than the median tumor H-score; or (b) a median 2+ or 3+ % TC derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% higher or lower than the median 2+ or 3+ % TC; (c) a tumor H-score of > 110, > 115, > 120, > 125, > 130, > 135, > 140, > 145, > 150, > 155, or > 160; or (d) 2+ or 3+ % TC of > 30%, > 35%, > 40%, > 45%, or > 50%.

72. The method of any one of claims 67-71, wherein the TIGIT antagonist is an anti-TIGIT antibody, the PD-(L) antagonist is an anti-PD-(L)1 antibody, or the TIGIT antagonist is an anti-TIGIT antibody and the PD-(L) antagonist is an anti-PD-(L)1 antibody.

73. The method of 72, wherein the anti-TIGIT antibody is (i) an Fc silent anti-TIGIT antibody, or (ii) domvanalimab.

74. The method of claim 72, wherein the anti-PD-(L)1 antibody is atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, nivolumab, pembrolizumab, spartalizumab, tremelimumab, or sasanlimab.

75. The method of any one of claims 47-54, 58, 59, 70, or 71, wherein CD155 staining intensity and percentage of staining positive cells are determined based on cytoplasmic staining and membrane staining.

76. The method of any one of claims 47-54, 58, 59, 70, or 71, wherein CD155 staining intensity and percentage of stained positive cells are determined based on membrane staining.

77. A method of treating a cancer in a patient having a high expression level of CXCL9, CXCL10, IL-6, or IFNy prior to treatment, the method comprising administering to the patient a combination therapy comprising a therapeutically effective amount of a TIGIT antagonist and a therapeutically effective amount of a PD-(L)l antagonist, wherein the high expression level of CXCL9, CXCL10, IL-6, or IFNy is an amount greater than or equal to a reference value.

78. The method of claim 77, wherein the reference value is a CD155 reference level that is a median value derived from samples obtained from a group of patients known to have the same cancer, or a value that is about 30%, about 25%, about 20%, about 15%, about 10%, or about 5% higher or lower than the median value.

79. The method of claim 77 or 78, wherein the TIGIT antagonist is an anti-TIGIT antibody, the PD-(L) antagonist is an anti-PD-(L)l antibody, or the TIGIT antagonist is an anti-TIGIT antibody and the PD-(L) antagonist is an anti-PD-(L)l antibody.

80. The method of 79, wherein the anti-TIGIT antibody is (i) an Fc silent anti-TIGIT antibody, or (ii) domvanalimumab.

81. The method of claim 79, wherein the anti-PD-(L)l antibody is atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, nivolumab, pembrolizumab, spartalizumab, tremelimumab, or sasanlimab.

82. The method of any one of claims 47-81, wherein the combination therapy further comprises chemotherapy.

83. The method of any one of claims 47-82, wherein the cancer is (i) Stage I, Stage II, or Stage III.

84. The method of claim 78, wherein the cancer is resectable and the combination therapy is administered prior to surgery (neoadjuvant therapy), after surgery (adjuvant therapy), or both prior to and after surgery (neoadjuvant plus adjuvant therapy).

85. The method of any one of claims 47-81, wherein the cancer is locally advanced or metastatic.

86. The method of claim 85, wherein the cancer is resectable and the combination therapy is administered prior to surgery (neoadjuvant therapy), after surgery (adjuvant therapy), or both prior to and after surgery (neoadjuvant plus adjuvant therapy).

87. The method of claim 85, wherein the locally advanced or metastatic cancer has not been previously treated, with the proviso that prior surgery is permitted.

88. The method of claim 85, wherein the locally advanced or metastatic cancer has not been previously treated with chemotherapy, optionally a chemotherapy comprising a platinum agent.

89. The method of claim 85, wherein the locally advanced or metastatic cancer was previously treated with chemotherapy, optionally a chemotherapy comprising a platinum agent.

90. The method of any one of claims 85, 87, 88, or 89, wherein the locally advanced or metastatic cancer was not previously treated with a PD-(L)l antagonist, optionally an anti-PD-(L)l antibody.

91. The method of any one of claims 86, 87, 88, or 89, wherein the locally advanced or metastatic cancer was previously treated with a PD-(L)l antagonist, optionally an anti-PD-(L)l antibody.

92. The method of any one of claims 47-91, wherein the cancer is a solid tumor.

93. The method of claim 92, wherein the cancer is selected from the group consisting of a gastrointestinal cancer, a genitourinary cancer, a gynecological cancer, a head and neck cancer, and a lung cancer.

94. The method of claim 93, wherein the cancer is a lung cancer or an upper gastrointestinal (GI) cancer.

95. The method of claim 94, wherein the cancer is squamous cell lung cancer, non-squamous cell lung cancer, gastric cancer, gastroesophageal junction (GEJ) cancer, esophageal adenocarcinoma (EAC), or esophageal squamous cell carcinoma (ESCC).

96. The method of claim 94, wherein the cancer is non-squamous cell lung cancer (NSCLC), gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (EAC).

97. The method of claim 92, wherein the cancer is selected from the group consisting of bladder cancer, breast cancer, endometrial cancer, head and neck squamous cell carcinoma, melanoma, ovarian cancer, and renal cell carcinoma.

98. The method of claim 92, wherein the cancer is selected from the group consisting of melanoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), head and neck squamous cell carcinoma (HNSCC), classical Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma (PMBCL), urothelial carcinoma, microsatellite instability-high or mismatch repair deficient cancer, microsatellite instability-high or mismatch repair deficient colorectal cancer (CRC), gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma (HCC), Merkel cell carcinoma (MCC), renal cell carcinoma (RCC), endometrial cancer, tumor mutational burden-high (TMB-H) cancer, cutaneous squamous cell carcinoma (cSCC), and triple-negative breast cancer (TNBC).

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