Method of treating cancer with a combination of an anti-CCR4 antibody and a 4-1BB agonist
The present disclosure describes combination therapies comprising an antibody which specifically binds to human CCR4 and a selective 4-1BB agonist, 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 an anti-CC chemokine receptor 4 (CCR4) antibody and a 4-1BB agonist, wherein the anti-CCR4 antibody comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6; and a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, a light chain CDR3 comprising SEQ ID NO: 3.
2. The method of claim 1 , wherein the anti-CCR4 antibody comprises a heavy chain and a light chain, wherein the heavy and light chains comprise SEQ ID NO: 15 and SEQ ID NO: 16, respectively; and wherein the 4-1BB agonist is a 4-1BB agonist 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.
3. The method of claim 1 , wherein the anti-CCR4 antibody comprises a heavy chain variable region comprising SEQ ID NO: 17; and a light chain variable region comprising SEQ ID NO: 18.
4. The method of claim 1 , wherein the anti-CCR4 antibody and the 4-1BB agonist are administered simultaneously and sequentially.
5. The method claim 1 , wherein the anti-CCR4 antibody is administered at a separate time from the 4-1 BB agonist.
6. The method of claim 1 , wherein the cancer is a solid tumor.
7. The method of claim 1 , wherein the cancer is head/neck squamous cell cancer, rectal cancer, colon cancer, squamous cell lung cancer, thyroid cancer, bladder cancer, melanoma, cervical cancer, prostate cancer, breast cancer, uterine/endometrial cancer, pancreatic cancer, lung adenocarcinoma, ovarian cancer, or papillary kidney cancer.
8. The method of claim 1 , wherein the anti-CCR4 antibody is administered at a dose of at least about 0.5 mg/kg, about 1 mg/kg, about 2 mg/kg, about 3 mg/kg, about 5 mg/kg, or about 10 mg/kg.
9. A method for treating cancer in an individual comprising administering to the individual an anti-CC chemokine receptor 4 (CCR4) antibody and a 4-1BB agonist, wherein the 4-1BB agonist comprises a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 28, a heavy chain CDR3 comprising SEQ ID NO: 29; and a light chain CDR1 comprising SEQ ID NO: 30, a light chain CDR2 comprising SEQ ID NO: 31, a light chain CDR3 comprising SEQ ID NO: 32.
10. The method of claim 9 , wherein the 4-1BB agonist comprises a heavy chain variable region comprising SEQ ID NO: 19; and a light chain variable region comprising SEQ ID NO: 20.
11. The method of claim 9 , wherein the anti-CCR4 antibody comprises a heavy chain and a light chain, wherein the heavy and light chains comprise SEQ ID NO: 15 and SEQ ID NO: 16, respectively; and wherein the 4-1BB agonist is a 4-1BB agonist 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.
12. The method of claim 9 , wherein the anti-CCR4 antibody and the 4-1BB agonist are administered simultaneously and sequentially.
13. The method of claim 9 , wherein the anti-CCR4 antibody is administered at a separate time from the 4-1BB agonist.
14. The method of claim 9 , wherein the cancer is a solid tumor.
15. The method of claim 9 , wherein the cancer is head/neck squamous cell cancer, rectal cancer, colon cancer, squamous cell lung cancer, thyroid cancer, bladder cancer, melanoma, cervical cancer, prostate cancer, breast cancer, uterine/endometrial cancer, pancreatic cancer, lung adenocarcinoma, ovarian cancer, or papillary kidney cancer.
16. A medicament comprising a combination of an anti-CC chemokine receptor 4 (CCR4) antibody and a 4-1BB agonist,
wherein the anti-CCR4 antibody comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6; and a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, a light chain CDR3 comprising SEQ ID NO: 3, or
wherein the 4-1BB agonist comprises a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 28, a heavy chain CDR3 comprising SEQ ID NO: 29; and a light chain CDR1 comprising SEQ ID NO: 30, a light chain CDR2 comprising SEQ ID NO: 31, a light chain CDR3 comprising SEQ ID NO: 32.
17. The medicament of claim 16 , wherein both or either of the anti-CCR4 antibody and the 4-1BB agonist are in the form of a pharmaceutical formulation to be administered simultaneously, sequentially, or concurrently.
18. The medicament of claim 16 , wherein the anti-CCR4 antibody comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6; and a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, a light chain CDR3 comprising SEQ ID NO: 3, and wherein the 4-1BB agonist comprises a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 28, a heavy chain CDR3 comprising SEQ ID NO: 29; and a light chain CDR1 comprising SEQ ID NO: 30, a light chain CDR2 comprising SEQ ID NO: 31, a light chain CDR3 comprising SEQ ID NO: 32.
19. A kit comprising a first container, a second container and a package insert, wherein the first container comprises at least one dose of a medicament comprising an anti-CC chemokine receptor 4 (CCR4) antibody, the second container comprises at least one dose of a medicament comprising a 4-1BB agonist, and the package insert comprises instructions for treating an individual for cancer using the medicaments; and
wherein the anti-CCR4 antibody comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6; and a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, a light chain CDR3 comprising SEQ ID NO: 3, or
wherein the 4-1BB agonist comprises a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 28, a heavy chain CDR3 comprising SEQ ID NO: 29; and a light chain CDR1 comprising SEQ ID NO: 30, a light chain CDR2 comprising SEQ ID NO: 31, a light chain CDR3 comprising SEQ ID NO: 32.
20. The kit of claim 19 , wherein the anti-CCR4 antibody comprises a heavy chain CDR1 comprising SEQ ID NO: 4, a heavy chain CDR2 comprising SEQ ID NO: 5, a heavy chain CDR3 comprising SEQ ID NO: 6; and a light chain CDR1 comprising SEQ ID NO: 1, a light chain CDR2 comprising SEQ ID NO: 2, a light chain CDR3 comprising SEQ ID NO: 3, and wherein the 4-1BB agonist comprises a heavy chain CDR1 comprising SEQ ID NO: 27, a heavy chain CDR2 comprising SEQ ID NO: 28, a heavy chain CDR3 comprising SEQ ID NO: 29; and a light chain CDR1 comprising SEQ ID NO: 30, a light chain CDR2 comprising SEQ ID NO: 31, a light chain CDR3 comprising SEQ ID NO: 32.
21. The kit of claim 19 , wherein the instructions state that the medicaments are intended for use in treating an individual having a cancer that tests positive for CCR4 expression.
22. The kit of claim 19 , wherein the cancer is head/neck squamous cell cancer, rectal cancer, colon cancer, squamous cell lung cancer, thyroid cancer, bladder cancer, melanoma, cervical cancer, prostate cancer, breast cancer, uterine/endometrial cancer, pancreatic cancer, lung adenocarcinoma, ovarian cancer, or papillary kidney cancer.
23. The kit of claim 19 , wherein the cancer is a solid tumor that tests positive for CCR4 expression and is selected from the group consisting of: head/neck squamous cell cancer, rectal cancer, colon cancer, squamous cell lung cancer, thyroid cancer, bladder cancer, melanoma, cervical cancer, prostate cancer, breast cancer, uterine/endometrial cancer, pancreatic cancer, lung adenocarcinoma, ovarian cancer, and papillary kidney cancer.
24. The kit of claim 19 , wherein the cancer is an advanced or metastatic solid tumor.