Combination of a PD-1 antagonist and a VEGF-R/FGFR/RET tyrosine kinase inhibitor for treating cancer
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a multi-RTK inhibitor, and the use of the combination therapies for the treatment of cancer. The multi-RTK inhibitor may be represented by Formula (I): wherein R 1 is C 1-6 alkyl or C 3-8 cycloalkyl, R 2 is a hydrogen atom or C 1-6 alkoxy, and R 3 is a hydrogen atom or a halogen atom. A tumor therapeutic agent is disclosed that combines a compound or pharmaceutically acceptable salt thereof represented by Formula I and an anti-PD-1 antibody.
1. A method for treating a cancer in an individual comprising administering to the individual a combination therapy which comprises an antagonist of a Programmed Death 1 protein (PD-1) and a multiple receptor tyrosine kinase (multi-RTK) inhibitor, wherein the antagonist is pembrolizumab, and wherein the multi-RTK inhibitor is lenvatinib or a pharmaceutically acceptable salt thereof, wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 5 to 200 mg, wherein the pembrolizumab is administered at a dose of 200 mg once every three weeks, and wherein the combination therapy is administered after an administration of lenvatinib or a pharmaceutically acceptable salt thereof, or is administered after an administration of pembrolizumab.
2. The method of claim 1 , wherein the individual is a human.
3. The method of claim 1 , wherein the cancer is a solid tumor.
4. The method of claim 1 , wherein the cancer is thyroid cancer, hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), endometrial cancer, urothelial cancer, squamous cell carcinoma of head and neck, glioblastoma, or melanoma.
5. The method of claim 1 , wherein the combination therapy which comprises pembrolizumab and lenvatinib or a pharmaceutically acceptable salt thereof is administered after an administration of lenvatinib or a pharmaceutically acceptable salt thereof for at least 7 days.
6. The method of claim 1 , comprising administering to the individual the combination therapy for at least 24 weeks, wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 24 mg, 20 mg or 14 mg, each as lenvatinib, and pembrolizumab is administered at a dose of 200 mg once every three weeks.
7. The method of claim 6 , wherein the cancer is thyroid cancer, HCC, NSCLC, RCC, endometrial cancer, urothelial cancer, squamous cell carcinoma of head and neck, glioblastoma, or melanoma.
8. The method of claim 4 , wherein the cancer is HCC.
9. The method of claim 7 , wherein the cancer is HCC.
10. The method of claim 4 , wherein the cancer is NSCLC.
11. The method of claim 7 , wherein the cancer is NSCLC.
12. The method of claim 11 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 20 mg, each as lenvatinib.
13. The method of claim 4 , wherein the cancer is RCC.
14. The method of claim 7 , wherein the cancer is RCC.
15. The method of claim 14 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 20 mg, each as lenvatinib.
16. The method of claim 4 , wherein the cancer is endometrial cancer.
17. The method of claim 7 , wherein the cancer is endometrial cancer.
18. The method of claim 17 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 20 mg, each as lenvatinib.
19. The method of claim 4 , wherein the cancer is squamous cell carcinoma of head and neck.
20. The method of claim 7 , wherein the cancer is squamous cell carcinoma of head and neck.
21. The method of claim 20 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 20 mg, each as lenvatinib.
22. The method of claim 4 , wherein the cancer is melanoma.
23. The method of claim 7 , wherein the cancer is melanoma.
24. The method of claim 23 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 20 mg, each as lenvatinib.
25. The method of claim 12 , wherein the pharmaceutically acceptable salt of lenvatinib is lenvatinib mesilate.
26. The method of claim 15 , wherein the pharmaceutically acceptable salt of lenvatinib is lenvatinib mesilate.
27. The method of claim 18 , wherein the pharmaceutically acceptable salt of lenvatinib is lenvatinib mesilate.
28. The method of claim 21 , wherein the pharmaceutically acceptable salt of lenvatinib is lenvatinib mesilate.
29. The method of claim 24 , wherein the pharmaceutically acceptable salt of lenvatinib is lenvatinib mesilate.
30. The method of claim 1 , wherein the dose of lenvatinib or a pharmaceutically acceptable salt thereof is selected based on the body weight of the patient.
31. The method of claim 1 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is formulated as a 4 mg or 10 mg lenvatinib capsule.
32. The method of claim 1 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 24 mg, 20 mg or 14 mg, each as lenvatinib.
33. The method of claim 1 , wherein the lenvatinib or a pharmaceutically acceptable salt thereof is administered at a daily dose of 5 to 24 mg.