A method of treating cancer using a combination of a PD-1 antagonist, a CTLA4 antagonist, and lenvatinib or a pharmaceutically acceptable salt thereof.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- MERCK SHARP & DOHME LLC
- Filing Date
- 2026-03-09
- Publication Date
- 2026-06-16
Smart Images
Figure 2026097988000001 
Figure 2026097988000002 
Figure 2026097988000003
Abstract
Claims
1. A method of treating cancer, for human patients who need it. (a) PD-1 antagonist, (b) CTLA-4 antagonist, and (c) Lenvatinib represented by formula (I) 【Chemistry 1】 A method comprising administering either or a pharmaceutically acceptable salt thereof.
2. The cancer is bladder cancer, breast cancer, non-small cell lung cancer, colorectal cancer, renal cell carcinoma (RCC), hepatocellular carcinoma. The method according to claim 1, selected from the group consisting of and melanoma.
3. The method according to claim 2, wherein the cancer is RCC.
4. The method according to claim 3, wherein the RCC is a progressing RCC.
5. The method according to claim 3, wherein the RCC is a transferable RCC.
6. The method according to claim 2, wherein the cancer is melanoma.
7. The method according to claim 6, wherein the melanoma is an advanced melanoma.
8. The method according to claim 6, wherein the melanoma is metastatic melanoma.
9. (a) PD-1 antagonist, (b) CTLA-4 antagonist, and (c) Lenvatinib represented by formula (I) 【Chemistry 2】 or a pharmaceutically acceptable salt thereof A kit that includes this.
10. The PD-1 antagonist, the CTLA-4 antagonist, and the formula (I) Therefore, lemvatinib 【Transformation 3】 or instructions for administering a pharmaceutically acceptable salt thereof to a human patient, further comprising: The kit according to claim 8.
11. The use of a therapeutic combination for treating cancer in human patients, wherein the therapeutic combination is (a) PD-1 antagonist, (b) CTLA-4 antagonist, and (c) Lenvatinib represented by formula (I) 【Chemistry 4】 Uses including those of a pharmaceutically acceptable salt thereof.
12. The cancer is bladder cancer, breast cancer, non-small cell lung cancer, colorectal cancer, renal cell carcinoma (RCC), hepatocellular carcinoma. The use according to claim 11, selected from the group consisting of and melanoma.
13. The use according to claim 12, wherein the cancer is RCC.
14. The use according to claim 12, wherein the cancer is melanoma.
15. The use according to claim 14, wherein the melanoma is an intractable melanoma.
16. The use according to claim 14, wherein the melanoma is a melanoma with brain metastasis.
17. The PD-1 antagonist is an anti-human PD-1 monoclonal antibody or its antigenic antibody. A composite fragment, the method, kit, or use according to any one of claims 1 to 16.
18. The PD-1 antagonist is an anti-human PD-L1 monoclonal antibody or its antigen. This is a binding fragment, where the anti-human PD-L1 monoclonal antibody is atezolizumab. There is no method, kit or use according to any one of claims 1 to 16.
19. The method according to claim 17, wherein the anti-human PD-1 monoclonal antibody is a humanized antibody. , kit or use.
20. The method according to claim 17, wherein the anti-human PD-1 monoclonal antibody is a human antibody. Kit or use.
21. The CTLA-4 antagonist is an anti-human CTLA4 monoclonal antibody or The method, kit, or use according to any one of claims 1 to 16, wherein the antigen-binding fragment is an antigen-binding fragment.
22. The claim 21 is described in which the anti-human CTLA-4 monoclonal antibody is a humanized antibody. Method, kit, or use.
23. The method according to claim 21, wherein the anti-human CTLA-4 monoclonal antibody is a human antibody. Law, kit or use.
24. Claim 17, wherein the anti-human PD-1 monoclonal antibody is pembrolizumab. Method, kit, or use.
25. The method according to claim 17, wherein the anti-human PD-1 monoclonal antibody is nivolumab. , kit or use.
26. The method according to claim 17, wherein the anti-human PD-1 monoclonal antibody is cemiprimab. Law, kit or use.
27. The aforementioned anti-human CTLA-4 monoclonal antibodies are described in SEQ ID NOs: 4, 5, and 6, respectively. V containing the amino acid sequence shown Ｌ CDR1, V Ｌ CDR2 and V Ｌ CDR3, and V containing the amino acid sequences described in SEQ ID NOs: 1, 2, and 3, respectively. Ｈ CDR1, V Ｈ CDR2 and V Ｈ The method, kit, or use according to claim 21, comprising CDR3.
28. The aforementioned anti-human CTLA-4 monoclonal antibody has the amino acid sequence described in SEQ ID NO: 14 Includes V Ｌ Region and V containing the amino acid sequence described in Sequence ID No. 15 Ｈ Including the area, bill The method, kit, or use described in item 21.
29. The aforementioned anti-human CTLA-4 monoclonal antibody has the amino acid sequence described in SEQ ID NO: 23 A light chain containing or consisting thereof, and containing or consisting of the amino acid sequence described in SEQ ID NO: 22 The method, kit, or use according to claim 21, comprising a heavy chain consisting thereof.
30. (a) The PD-1 antagonist is pembrolizumab, (b) The CTLA-4 antagonist is described in Sequence ID No. 4, 5, and 6, respectively. V containing an amino acid sequence Ｌ CDR1, V Ｌ CDR2 and V Ｌ CDR3, respectively V containing the amino acid sequences described in SEQ ID NOs: 1, 2, and 3 Ｈ CDR1, V Ｈ CDR2 Call V Ｈ A monoclonal antibody containing CDR3 or its antigen-binding fragment, The method, kit, or use according to any one of claims 1 to 16.
31. (a) The PD-1 antagonist is nivolumab, and (b) The CTLA-4 antagonist is described in Sequence ID No. 4, 5, and 6, respectively. V containing amino acid sequence Ｌ CDR1, V Ｌ CDR2 and V Ｌ CDR3 and each V containing the amino acid sequences described in SEQ ID NOs: 1, 2, and 3 Ｈ CDR1, V Ｈ CDR2 Call V Ｈ A monoclonal antibody containing CDR3 or its antigen-binding fragment, The method, kit, or use according to any one of claims 1 to 16.
32. (a) The PD-1 antagonist is semiprimab, and, (b) The CTLA-4 antagonist is described in Sequence ID No. 4, 5, and 6, respectively. V containing amino acid sequence Ｌ CDR1, V Ｌ CDR2 and V Ｌ CDR3 and each V containing the amino acid sequences described in SEQ ID NOs: 1, 2, and 3 Ｈ CDR1, V Ｈ CDR2 Call V Ｈ A monoclonal antibody containing CDR3 or its antigen-binding fragment, The method, kit, or use according to any one of claims 1 to 16.
33. The aforementioned human patients were given 200 mg, 240 mg, 400 mg, or 2 mg / kg of Pembal. Lolizumab is administered, and then pembrolizumab is administered once every six weeks. The method described in item 30.
34. The aforementioned human patient was administered 400 mg of pembrolizumab, and here, pembrolizumab The method according to claim 30, wherein lizumab is administered once every six weeks.
35. The aforementioned human patients were given 240 mg or 3 mg / kg of nivolumab once every two weeks. The method according to claim 31, wherein 480 mg of nivolumab is administered once every four weeks.
36. The aforementioned human patient was administered 350 mg of cemiprimab, and here, cemiprimab The method according to claim 32, wherein the drug is administered once every three weeks.
37. The aforementioned human patient was administered approximately 1 mg to approximately 200 mg of the anti-human CTLA-4 antibody. Claims 33-36 further state that the anti-human CTLA4 antibody is administered once every six weeks. The method described in any one of the items.
38. The aforementioned human patients received 1, 1.25, 1.4, 2.0, 2.5, 2.9, 5, 7.9, and 10 doses. , before 12.5, 25, 50, 75, 100, 125, 150, 175 or 200 mg The anti-human CTLA-4 antibody was administered, and here, the anti-human CTLA-4 antibody was 3 The method according to claim 37, administered once a week.
39. Claim 38, wherein 25 mg of the anti-human CTLA-4 antibody is administered to the human patient. Method of description.
40. The aforementioned human patients were given 8, 10, 12, 14, 18, 20, or 24 mg of lenvatinib. Or a pharmaceutically acceptable salt thereof is administered, and here, lenvatinib or the said A pharmaceutically acceptable salt is administered once daily, according to any one of claims 33 to 39. method.
41. A method for treating melanoma, for human patients who need it. (a) 400 mg of pembrolizumab, (b) V containing the amino acid sequences described in SEQ ID NOs: 4, 5, and 6, respectively. Ｌ CDR1, V Ｌ CDR2 and V Ｌ CDR3 and the mesh described in Sequence IDs 1, 2, and 3, respectively. V containing an acid sequence Ｈ CDR1, V Ｈ CDR2 and V Ｈ Including CDR3, 25m g of anti-human CTLA-4 monoclonal antibody or its antigen-binding fragment, and (c) A method comprising administering 20 mg of lenvatinib.
42. The method according to claim 41, wherein each of (a) and (b) is administered once every six weeks.
43. The method according to claims 41 to 42, wherein (c) is administered once a day.
44. (a) and (b) are administered on the same day, and (a) and (b) are administered consecutively or simultaneously. The method according to claim 41.
45. Claims 1 to 32, wherein the pharmaceutically acceptable salt is lenvatinib mesylate. Any method, kit, or use described in one of the items.