Combination of a PD-1 antagonist and a VEGFR inhibitor for treating cancer
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a VEGFR inhibitor, and the use of the combination therapies for the treatment of cancer, and in particular for treating cancers that express PD-L1.
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 vascular endothelial growth factor receptor (VEGFR) inhibitor, wherein the PD-1 antagonist is an anti-PD-1 monoclonal antibody which comprises a heavy chain and a light chain, wherein the heavy and light chains comprise SEQ ID NO:21 and SEQ ID NO:22, respectively, and further wherein the VEGFR inhibitor is N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide or a pharmaceutically acceptable salt thereof.
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 renal cell carcinoma.
5. The method of claim 1 , wherein the PD-1 antagonist is Pembrolizumab and the VEGFR inhibitor is axitinib.
6. A kit which comprises a first container, a second container and a package insert, wherein the first container comprises at least one dose of a medicament comprising an antagonist of a Programmed Death 1 protein (PD-1), the second container comprises at least one dose of a medicament comprising a vascular endothelial growth factor receptor (VEGFR) inhibitor, and the package insert comprises instructions for treating an individual for cancer using the medicaments, wherein the PD-1 antagonist is an anti-PD-1 monoclonal antibody which comprises a heavy chain and a light chain, wherein the heavy and light chains comprise SEQ ID NO:21 and SEQ ID NO:22, respectively, and further wherein the VEGFR inhibitor is N-methyl-2-[3-((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]-benzamide or a pharmaceutically acceptable salt thereof.
7. The kit of claim 6 , wherein the instructions state that the medicaments are intended for use in treating an individual having a cancer that tests positive for Program Death-Ligand 1 (PD-L1) expression by an immunohistochemical (IHC) assay.
8. The kit of claim 6 , wherein the individual is a human.
9. The kit of claim 6 , wherein the PD-1 antagonist is Pembrolizumab formulated as a liquid medicament and the VEGFR inhibitor is axitinib formulated as a 1 mg tablet or a 5 mg tablet.
10. The method of claim 1 , wherein the cancer is bladder cancer, breast cancer, clear cell kidney cancer, head/neck squamous cell carcinoma, lung squamous cell carcinoma, malignant melanoma, non-small-cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, prostate cancer, renal cell cancer, small-cell lung cancer (SCLC), triple negative breast cancer, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, Hodgkin's lymphoma (HL), mantle cell lymphoma (MCL), multiple myeloma (MM), myelodysplastic syndrome (MDS), non-Hodgkin's lymphoma (NHL), or small lymphocytic lymphoma (SLL).
11. The method of claim 10 , wherein the cancer is advanced renal cell carcinoma.
12. A method for treating a human individual diagnosed with a cancer, comprising administering to the individual a combination therapy which comprises Pembrolizumab and axitinib, wherein (a) axitinib is administered at a dose of 5 mg twice daily (BID) and Pembrolizumab is administered at a dose selected from the group consisting of 1 mg/kg every three weeks (Q3W), 2 mg/kg Q3W and 200 mg Q3W or (b) axitinib is administered at a dose of 3 mg BID and Pembrolizumab is administered at a dose selected from the group consisting of 1 mg/kg Q3W, 2 mg/kg Q3W and 200 mg Q3W.
13. The kit of claim 6 , wherein the cancer is bladder cancer, breast cancer, clear cell kidney cancer, head/neck squamous cell carcinoma, lung squamous cell carcinoma, malignant melanoma, non-small-cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, prostate cancer, renal cell cancer, small-cell lung cancer (SCLC), triple negative breast cancer, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, Hodgkin's lymphoma (HL), mantle cell lymphoma (MCL), multiple myeloma (MM), myelodysplastic syndrome (MDS), non-Hodgkin's lymphoma (NHL), or small lymphocytic lymphoma (SLL).
14. The method of claim 12 , wherein said cancer is renal cell carcinoma.
15. The method of claim 12 , wherein said Pembrolizumab is provided at a dose of 200 mg Q3W.
16. The method for treating a human individual diagnosed with a cancer of claim 12 , comprising administering to the individual a combination therapy which comprises Pembrolizumab and axitinib, wherein axitinib is administered at a dose of 5 mg twice daily (BID) and Pembrolizumab is administered at a dose of 1 mg/kg every three weeks (Q3W).
17. The method for treating a human individual diagnosed with a cancer of claim 12 , comprising administering to the individual a combination therapy which comprises Pembrolizumab and axitinib, wherein axitinib is administered at a dose of 5 mg twice daily (BID) and Pembrolizumab is administered at a dose of 2 mg/kg Q3W.
18. The method for treating a human individual diagnosed with a cancer of claim 12 , comprising administering to the individual a combination therapy which comprises Pembrolizumab and axitinib, wherein axitinib is administered at a dose of 5 mg twice daily (BID) and Pembrolizumab is administered at a dose of 200 mg Q3W.
19. The method for treating a human individual diagnosed with a cancer of claim 12 , comprising administering to the individual a combination therapy which comprises Pembrolizumab and axitinib, wherein axitinib is administered at a dose of 3 mg twice daily (BID) and Pembrolizumab is administered at a dose of 1 mg/kg every three weeks (Q3W).
20. The method for treating a human individual diagnosed with a cancer of claim 12 , comprising administering to the individual a combination therapy which comprises Pembrolizumab and axitinib, wherein axitinib is administered at a dose of 3 mg twice daily (BID) and Pembrolizumab is administered at a dose of 2 mg/kg Q3W.
21. The method for treating a human individual diagnosed with a cancer of claim 12 , comprising administering to the individual a combination therapy which comprises Pembrolizumab and axitinib, wherein axitinib is administered at a dose of 3 mg twice daily (BID) and Pembrolizumab is administered at a dose of 200 mg Q3W.
22. The kit of claim 9 , wherein the PD-1 antagonist is Pembrolizumab formulated as a liquid medicament and the VEGFR inhibitor is axitinib formulated as a 1 mg tablet.
23. The kit of claim 9 , wherein the PD-1 antagonist is Pembrolizumab formulated as a liquid medicament and the VEGFR inhibitor is axitinib formulated as a 5 mg tablet.
24. A method for treating renal cell carcinoma 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 vascular endothelial growth factor receptor (VEGFR) inhibitor, wherein the PD-1 antagonist is Pembrolizumab, and further wherein the VEGFR inhibitor is axitinib.
25. A method for treating advanced renal cell carcinoma 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 vascular endothelial growth factor receptor (VEGFR) inhibitor, wherein the PD-1 antagonist is Pembrolizumab, and further wherein the VEGFR inhibitor is axitinib.
26. The method of claim 1 , wherein the PD-1 antagonist is Pembrolizumab.