Claims for Patent: 12,678,498

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Summary for Patent: 12,678,498

Title:	FGFR/PD-1 combination therapy for the treatment of cancer
Abstract:	Provided herein are combination therapies for the treatment of cancer. In particular, the disclosed methods are directed to treatment of cancer in a patient comprising administering an antibody that blocks the interaction between PD-1 and PD-L1 and an FGFR inhibitor, wherein the antibody that blocks the interaction between PD-1 and PD-L1 and the FGFR inhibitor are administered if one or more FGFR variants are present in a biological sample from the patient.
Inventor(s):	Jayaprakash Karkera, Suso Jesus PLATERO, Raluca Verona, Matthew V. Lorenzi
Assignee:	Janssen Pharmaceutica NV , Astex Therapeutics Ltd
Application Number:	US17/655,519
Patent Claims:	1. A method of treating cancer in a patient comprising: administering to the patient a pharmaceutically effective amount of an antibody that blocks the interaction between PD-1 and PD-L1; monitoring the efficacy of the antibody; and if the antibody is not efficacious, evaluating a biological sample from the patient for a presence of one or more FGFR variants, wherein the one or more FGFR variants comprise an FGFR mutation, and wherein the FGFR mutation is FGFR3 G370C; and administering to the patient a pharmaceutically effective amount of an FGFR inhibitor if the one or more FGFR variants are present in the sample, wherein the FGFR inhibitor is the compound of formula (I): or a pharmaceutically acceptable salt thereof. 2. The method of claim 1, wherein the evaluating step further comprises measuring an expression level of PD-L1 in a biological sample and wherein the second administering step comprises administering the FGFR inhibitor if: the biological sample has a PD-L1 expression corresponding to an H-score of about 0 to about 99; or the biological sample has a PD-L1 expression level that is lower than a reference PD-L1 expression level. 3. The method of claim 1, wherein the biological sample is blood, lymph fluid, bone marrow, a solid tumor sample, or any combination thereof. 4. The method of claim 1, wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof. 5. The method of claim 4, wherein the cancer is bladder cancer. 6. The method of claim 1, wherein the one or more FGFR variants further comprise an FGFR fusion gene. 7. The method of claim 1, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 R248C. 8. The method of claim 1, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 S249C. 9. The method of claim 1, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 Y373C. 10. The method of claim 1, wherein the antibody that blocks an interaction between PD-1 and PD-L1 is an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof. 11. The method of claim 2, wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof. 12. The method of claim 11, wherein the cancer is bladder cancer. 13. The method of claim 2, wherein the one or more FGFR variants further comprise an FGFR fusion gene. 14. The method of claim 2, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 R248C. 15. The method of claim 2, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 S249C. 16. The method of claim 2, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 Y373C. 17. The method of claim 2, wherein the antibody that blocks an interaction between PD-1 and PD-L1 is an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof. 18. The method of claim 3, wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof. 19. The method of claim 18, wherein the cancer is bladder cancer. 20. The method of claim 3, wherein the one or more FGFR variants further comprise an FGFR fusion gene. 21. The method of claim 3, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 R248C. 22. The method of claim 3, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 S249C. 23. The method of claim 3, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 Y373C. 24. The method of claim 3, wherein the antibody that blocks an interaction between PD-1 and PD-L1 is an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof. 25. The method of claim 1, wherein the biological sample: has a PD-L1 expression corresponding to an H-score of less than 20; or has a PD-L1 expression level that is lower than a reference PD-L1 expression level. 26. The method of claim 25, where the biological sample has a PD-L1 expression corresponding to an H-score of less than 20. 27. The method of claim 1, wherein the FGFR inhibitor is the compound of formula (I): 28. The method of claim 27, wherein the cancer is lung cancer, bladder cancer, gastric cancer, breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, glioblastoma, or any combination thereof. 29. The method of claim 28, wherein the cancer is bladder cancer. 30. The method of claim 29, wherein the one or more FGFR variants further comprise an FGFR fusion gene. 31. The method of claim 29, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 R248C. 32. The method of claim 29, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 S249C. 33. The method of claim 29, wherein the one or more FGFR variants comprise at least one additional FGFR mutation, which is FGFR3 Y373C. 34. The method of claim 29, wherein the antibody that blocks an interaction between PD-1 and PD-L1 is an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination thereof. 35. The method of claim 29, wherein the biological sample is a solid tumor sample. 36. The method of claim 3, wherein the biological sample is a solid tumor sample.