Methods and compositions for predicting the therapeutic effectiveness of cancer treatment and prognosis of cancer

Claims

1. Method of determination (i) whether a patient with cancer who has a tumor antigen-positive tumor responds to treatment with an antibody against the tumor antigen and / or (ii) whether the cancer patient will have a progression-free survival period, preferably in a cancer patient who has a tumor antigen-positive tumor, wherein said method includes determining the genotype for one or more single nucleotide polymorphisms selected from the group consisting of FCGR2A rs1801274, MUC1 rs4072037, IL-10 rs1800896, DNMT3A rs1550117, SMAD4 rs12456284, EGF rs4444903, CDH1 rs16260, ERCC1 rs11615 and FCGR3A rs396991 in a sample obtained from a patient.

2. The method according to claim 1, characterized in that the presence of the heterozygous genotype FCGR2A rs1801274 [CT] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

3. The method according to claim 1, characterized in that the presence of the homozygous genotype FCGR2A rs1801274 [TT] and / or the homozygous genotype FCGR2A rs1801274 [CC] indicates an increased risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or an increased risk that the patient with an oncological disease will not have a progression-free survival period.

4. The method according to claim 1, characterized in that the presence of the homozygous genotype MUC1 rs4072037 [AA] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

5. The method according to claim 1, characterized in that the presence of the homozygous genotype MUC1 rs4072037 [GG] indicates an increased risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or an increased risk that the patient with an oncological disease will not have a period of progression-free survival.

6. The method according to claim 1, characterized in that the presence of the homozygous genotype IL-10 rs1800896 [GG] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

7. The method according to claim 1, characterized in that the presence of a heterozygous genotype DNMT3A rs1550117 [GA] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

8. The method according to claim 1, characterized in that the presence of the heterozygous genotype SMAD4 rs12456284 [GA] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

9. The method according to claim 1, characterized in that the presence of the homozygous genotype EGF rs4444903 [AA] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

10. The method according to claim 1, characterized in that the presence of the homozygous genotype CDH1 rs16260 [AA] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

11. The method according to claim 1, characterized in that the presence of the homozygous genotype ERCC1 rs11615 [TT] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

12. The method according to claim 1, characterized in that the presence of the heterozygous genotype FCGR3A rs396991 [TG] and / or the homozygous genotype FCGR3A rs396991 [TT] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a progression-free survival period.

13. The method according to any one of paragraphs 1-12, characterized in that the tumor antigen is the CLDN18.2 protein.

14. Method of determination (i) whether the cancer patient with a CLDN18.2-positive tumor is a responder to treatment with an antibody against the CLDN18.2 protein and / or (ii) whether a patient with cancer, preferably a patient with cancer who has a CLDN18.2-positive tumor, will have progression-free survival, wherein said method comprises determining the genotype for one or more single nucleotide polymorphisms selected from the group consisting of FCGR2A rs1801274, MUC1 rs4072037, IL-10 rs1800896, DNMT3A rs1550117, SMAD4 rs12456284, EGF rs4444903, CDH1 rs16260, ERCC1 rs11615 and FCGR3A rs396991 in a sample obtained from a patient.

15. The method according to claim 14, characterized in that the presence of the heterozygous genotype FCGR2A rs1801274 [CT] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

16. The method according to claim 14, characterized in that the presence of the homozygous genotype FCGR2A rs1801274 [TT] and / or the homozygous genotype FCGR2A rs1801274 [CC] indicates an increased risk that the patient with an oncological disease will not be a responder to treatment with an antibody and / or an increased risk that the patient with an oncological disease will not have a progression-free survival period.

17. The method of claim 14, wherein the presence of the homozygous genotype MUC1 rs4072037 [AA] indicates a reduced risk that the cancer patient is not a responder to treatment with the antibody and / or a reduced risk that the cancer patient will not achieve progression-free survival.

18. The method of claim 14, wherein the presence of the homozygous genotype MUC1 rs4072037 [GG] indicates an increased risk that the patient with cancer will not be a responder to treatment with the antibody and / or an increased risk that the patient with cancer will not have a progression-free survival period.

19. The method according to claim 14, characterized in that the presence of the homozygous genotype IL-10 rs1800896 [GG] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

20. The method according to claim 14, characterized in that the presence of a heterozygous genotype DNMT3A rs1550117 [GA] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

21. The method according to claim 14, characterized in that the presence of the heterozygous genotype SMAD4 rs12456284 [GA] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

22. The method of claim 14, wherein the presence of the homozygous genotype EGF rs4444903 [AA] indicates a reduced risk that the patient with cancer is not a responder to treatment with the antibody and / or a reduced risk that the patient with cancer will not have a progression-free survival period.

23. The method according to claim 14, characterized in that the presence of the homozygous genotype CDH1 rs16260 [AA] indicates a reduced risk that the patient with cancer is not a responder to treatment with the antibody and / or a reduced risk that the patient with cancer will not have a period of progression-free survival.

24. The method according to claim 14, characterized in that the presence of the homozygous genotype ERCC1 rs11615 [TT] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

25. The method according to claim 14, characterized in that the presence of the heterozygous genotype FCGR3A rs396991 [TG] and / or the homozygous genotype FCGR3A rs396991 [TT] indicates a reduced risk that the patient with an oncological disease is not a responder to treatment with an antibody and / or a reduced risk that the patient with an oncological disease will not have a period of progression-free survival.

26. The method according to any one of claims 1-25, characterized in that the antibody acts by recruiting the patient's immune system to destroy tumor cells.

27. The method according to any one of claims 1-26, characterized in that the antibody acts through antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement-dependent cytotoxicity (CDC).

28. The method according to any one of paragraphs 1-27, characterized in that the antibody is a monoclonal antibody.

29. The method according to any one of claims 1-28, characterized in that the antibody comprises a heavy chain comprising an amino acid sequence represented by SEQ ID NO: 17 or 51, or a fragment thereof, and a light chain comprising an amino acid sequence represented by SEQ ID NO: 24, or a fragment thereof.

30. The method according to any one of claims 1-29, characterized in that the non-response to treatment with the antibody includes a relative decrease in one or more of survival, progression-free survival, relapse-free survival, delayed relapse-free survival, and stable disease.

31. A method for treating a patient with an oncological disease, wherein said method includes a. assessing whether a patient with cancer is a responder to treatment with an antibody using the method of any one of paragraphs 1-30 and b. (i) treating a patient with cancer with an antibody if the patient has a reduced risk of not responding to treatment with the antibody or (ii) not treating a patient with cancer with an antibody and / or treating a patient with cancer with a treatment regimen that includes treatment other than treatment with the antibody if the patient has an increased risk of not responding to treatment with the antibody.

32. The method according to claim 31, characterized in that the treatment regimen includes treatment that is independent of the patient’s immune system.

33. The method according to claim 31 or 32, characterized in that the treatment regimen does not include treatment with an antibody that acts by recruiting the patient's immune system to destroy tumor cells.

34. The method according to any one of paragraphs 31-33, characterized in that the treatment regimen includes surgery, chemotherapy and / or radiation.

35. The method according to any one of paragraphs 31-34, characterized in that the treatment regimen includes treatment with a low molecular weight inhibitor of a tumor antigen and / or an antibody-drug conjugate, wherein the antibody is directed against a tumor antigen.

36. The method of claim 35, wherein the antibody-drug conjugate is an antibody linked to a radioactive, chemotherapeutic, or toxin component.

37. The method according to claim 35 or 36, characterized in that the antibody-drug conjugate is an antibody linked to a cytostatic or cytotoxic compound.

38. A method for assessing a clinical outcome for a patient with an oncological disease, wherein said method includes determining the genotype for one or more single nucleotide polymorphisms selected from the group consisting of FCGR2A rs1801274, MUC1 rs4072037, IL-10 rs1800896, DNMT3A rs1550117, SMAD4 rs12456284, EGF Rs4444903, CDH1 rs16260, ERCC1 rs11615 and FCGR3A rs396991 in a sample obtained from the patient.

39. The method according to claim 38, characterized in that the presence of the heterozygous genotype FCGR2A rs1801274 [CT] indicates a reduced risk of an unfavorable clinical outcome.

40. The method according to claim 38, characterized in that the presence of the homozygous genotype FCGR2A rs1801274 [TT] and / or the homozygous genotype FCGR2A rs1801274 [CC] indicates an increased risk of an unfavorable clinical outcome.

41. The method according to claim 38, characterized in that the presence of the homozygous genotype MUC1 rs4072037 [AA] indicates a reduced risk of an unfavorable clinical outcome.

42. The method according to claim 38, characterized in that the presence of the homozygous genotype MUC1 rs4072037 [GG] indicates an increased risk of an unfavorable clinical outcome.

43. The method according to claim 38, characterized in that the presence of the homozygous genotype IL-10 rs1800896 [GG] indicates a reduced risk of an unfavorable clinical outcome.

44. The method according to claim 38, characterized in that the presence of the heterozygous genotype DNMT3A rs1550117 [GA] indicates a reduced risk of an unfavorable clinical outcome.

45. The method according to claim 38, characterized in that the presence of the heterozygous genotype SMAD4 rs12456284 [GA] indicates a reduced risk of an unfavorable clinical outcome.

46. ​​The method according to claim 38, characterized in that the presence of the homozygous genotype EGF rs4444903 [AA] indicates a reduced risk of an unfavorable clinical outcome.

47. The method according to claim 38, characterized in that the presence of the homozygous genotype CDH1 rs16260 [AA] indicates a reduced risk of an unfavorable clinical outcome.

48. The method according to claim 38, characterized in that the presence of the homozygous genotype ERCC1 rs11615 [TT] indicates a reduced risk of an unfavorable clinical outcome.

49. The method according to claim 38, characterized in that the presence of the heterozygous genotype FCGR3A rs396991 [TG] and / or the homozygous genotype FCGR3A rs396991 [TT] indicates a reduced risk of an unfavorable clinical outcome.

50. The method according to any one of paragraphs 38-49, characterized in that the assessment of the clinical outcome for a patient with an oncological disease includes predicting the probability of one or more of survival, progression-free survival, relapse-free survival, delayed relapse-free survival, and stable disease.

51. The method according to any one of paragraphs 39-49, characterized in that the unfavorable clinical outcome includes a relative decrease in one or more of survival, progression-free survival, relapse-free survival, delayed relapse-free survival, and stable disease.

52. The method according to any one of paragraphs 38-51, characterized in that the patient has an antigen-positive tumor and receives treatment with an antibody against the tumor antigen.

53. The method according to any one of paragraphs 1-52, characterized in that the sample is a sample containing DNA.

54. The method according to claim 53, characterized in that the DNA is extracted from a sample of the patient’s body.

55. The method according to claim 53 or 54, characterized in that the DNA was extracted from blood.

56. The method according to any one of paragraphs 1-55, characterized in that the tumor is a solid tumor.

57. The method according to any one of paragraphs 1-56, characterized in that the tumor is a gastroesophageal tumor.

58. The method according to any one of paragraphs 1-57, characterized in that the tumor is a progressive adenocarcinoma of the stomach or lower esophagus.

59. The method according to any one of paragraphs 1-58, characterized in that the malignant neoplasm is gastroesophageal cancer.

60. The method according to any one of paragraphs 1-59, characterized in that the malignant neoplasm is a progressive adenocarcinoma of the stomach or lower esophagus.