Combination of a PD-1 antagonist and CPG-C type oligonucleotide for treating cancer
The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1) and a Toll-like receptor 9 (TLR9) agonist that is a CpG-C type oligonucleotide, and the use of the combination therapies for the treatment of cancer.
1. A method for treating cancer in an individual comprising administering to the individual a PD-1 antagonist and a TLR9 agonist,
wherein the TLR9 agonist is a CpG-C type oligonucleotide having a sequence consisting of 5′-TCGAACGTTCGAACGTTCGAACGTTCGAAT-3′ (SEQ ID NO: 45), and wherein the PD-1 antagonist is:
(i) a monoclonal antibody, or antigen binding fragment thereof, which comprises light chain CDRs of SEQ ID NOs: 7, 8 and 9 and heavy chain CDRs of SEQ ID NOs: 10, 11 and 12, or
(ii) an anti-PD-1 monoclonal antibody which comprises a heavy chain and a light chain, and wherein the heavy chain comprises SEQ ID NO: 21 and the light chain comprises SEQ ID NO: 22.
2. The method of treating cancer of claim 1 , wherein the CpG-C type oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
3. The method of treating cancer of claim 1 , wherein the cancer is a bladder cancer, a breast cancer, a clear cell kidney cancer, a head/neck a squamous cell carcinoma, a lung squamous cell carcinoma, a malignant melanoma, a non-small-cell lung cancer (NSCLC), an ovarian cancer, a pancreatic cancer, a prostate cancer, a renal cell cancer, a small-cell lung cancer (SCLC), or a triple negative breast cancer.
4. The method of treating cancer of claim 1 , wherein the cancer is advanced or metastatic melanoma.
5. The method of treating cancer of claim 1 , wherein the cancer tests positive for human PD-L1.
6. The method of treating cancer of claim 1 , wherein the PD-1 antagonist is pembrolizumab.
7. The method of treating cancer of claim 6 , wherein the pembrolizumab is administered at a dose of 200 mg once every three weeks and the oligonucleotide of SEQ ID NO: 45 is intratumorally administered at a dose of from 1 to 16 mg once a week.
8. The method of treating cancer of claim 6 , wherein the pembrolizumab is administered at a dose of 200 mg once every three weeks and the oligonucleotide of SEQ ID NO: 45 is intratumorally administered at a dose of from 1 to 16 mg once every three weeks.
9. The method of treating cancer of claim 7 , wherein the individual is confirmed progressive while receiving prior anti-PD-1 therapy.
10. The method of treating cancer of claim 8 , wherein the individual is confirmed progressive while receiving prior anti-PD-1 therapy.
11. The method of treating cancer of claim 7 , wherein the oligonucleotide is injected intratumorally at a dose of 2.0, 4.0, or 8.0 mg.
12. The method of treating cancer of claim 8 , wherein the oligonucleotide is injected intratumorally at a dose of 2.0, 4.0, or 8.0 mg.
13. The method of treating cancer of claim 7 , wherein the individual has not been previously treated for the cancer with an anti-PD-1 therapy or an anti-PD-L1 therapy.
14. The method of treating cancer of claim 8 , wherein the individual has not been previously treated for the cancer with an anti-PD-1 therapy or an anti-PD-L1 therapy.
15. The method of treating cancer of claim 1 , wherein the cancer is an advanced or metastatic melanoma, a renal cell carcinoma, a non-small cell lung cancer, a bladder cancer, or a colorectal cancer.
16. The method of treating cancer of claim 1 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
17. The method of treating cancer of claim 2 , wherein the CpG-C type oligonucleotide is a sodium salt.
18. The method of treating cancer of claim 3 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
19. The method of treating cancer of claim 4 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
20. The method of treating cancer of claim 5 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
21. The method of treating cancer of claim 6 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
22. The method of treating cancer of claim 7 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
23. The method of treating cancer of claim 8 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
24. The method of treating cancer of claim 9 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
25. The method of treating cancer of claim 10 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
26. The method of treating cancer of claim 11 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
27. The method of treating cancer of claim 12 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.
28. The method of treating cancer of claim 13 , wherein the CpG-C type oligonucleotide is a sodium salt, and the oligonucleotide is an oligodeoxynucleotide with a phosphorothioate backbone.