METHODS FOR TREATING CANCER WITH ANTI PD-1 ANTIBODIES AND ANTI CTLA4 ANTIBODIES

1 - 31 . (canceled)

32 . A method of treating cancer in a human patient comprising administering about 400 mg of an anti-PD-1 antibody or antigen binding fragment thereof to the patient approximately every six weeks and about 25 mg, about 50 mg, about 75 mg, or about 100 mg of an anti-CTLA4 antibody or antigen binding fragment thereof to the patient approximately every six weeks, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises:

(a) light chain complementarity determining regions (CDRs) comprising a sequence of amino acids as set forth in SEQ ID NOs: 1, 2 and 3 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 6, 7 and 8; or

(b) light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 11, 12 and 13 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 14, 15 and 16;

and wherein the anti-CTLA4 antibody or antigen binding fragment thereof comprises:

(a) light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 39, 40 and 41 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 36, 37, and 38;

(b) light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 39, 40 and 42 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 36, 37, and 38; or

(c) light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 39, 40 and 43 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 36, 37, and 38.

33 . The method of claim 32 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises:

(a) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:9, or a variant of SEQ ID NO:9, and

(b) a light chain variable region comprising:

(i) a sequence of amino acids as set forth in SEQ ID NO:4, or a variant of SEQ ID NO:4,

(ii) a sequence of amino acids as set forth in SEQ ID NO:22, or a variant of SEQ ID NO:22, or

(iii) a sequence of amino acids as set forth in SEQ ID NO:23, or a variant of SEQ ID NO:23.

34 . The method of claim 33 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:9 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:4.

35 . The method of claim 32 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is a monoclonal antibody comprising:

(a) a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:10, or a variant of SEQ ID NO:10, and

(b) a light chain comprising a sequence of amino acids as set forth in SEQ ID NO:5, a variant of SEQ ID NO:5, SEQ ID NO:24, a variant of SEQ ID NO:24, SEQ ID NO:25, or a variant of SEQ ID NO:25.

36 . The method of claim 35 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is a monoclonal antibody comprising a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:10 and a light chain comprising a sequence of amino acids as set forth in SEQ ID NO:5.

37 . The method of claim 32 , wherein the anti-CTLA4 antibody or antigen binding fragment thereof is comprising

(a) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:44 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:45;

(b) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:46 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:47;

(c) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:48 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:49;

(d) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:50 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:49;

(e) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:51 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:52;

(f) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:53 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:54; or

(g) a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:55 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:56.

38 . The method of claim 37 , wherein the anti-CTLA4 antibody or antigen binding fragment thereof comprises a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:50 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:49.

39 . The method of claim 37 , wherein the anti-CTLA4 antibody or antigen binding fragment thereof comprises a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:57 and a light chain comprising a sequence of amino acids as set forth in SEQ ID NO:58.

40 . A method of treating cancer in a human patient comprising administering about 400 mg of an anti-PD-1 antibody and about 25 mg, about 50 mg, about 75 mg, or about 100 mg of an anti-CTLA4 antibody, each to the patient approximately every six weeks, wherein the anti-PD-1 antibody comprises (i) a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:10 and (ii) a light chain comprising a sequence of amino acids as set forth in SEQ ID NO:5, and wherein the anti-CTLA4 antibody comprises (iii) a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:57 and (iv) a light chain comprising a sequence of amino acids as set forth in SEQ ID NO:58.

41 . The method of claim 32 , wherein the cancer is PD-1/PD-L1 refractory melanoma.

42 . The method claim 32 , wherein the cancer is selected from the group consisting of: melanoma, non-small cell lung cancer, head and neck cancer, urothelial cancer, breast cancer, gastrointestinal cancer, multiple myeloma, hepatocellular cancer, non-Hodgkin lymphoma, renal cancer, Hodgkin lymphoma, mesothelioma, ovarian cancer, small cell lung cancer, esophageal cancer, anal cancer, biliary tract cancer, colorectal cancer, cervical cancer, thyroid cancer, salivary cancer, pancreatic cancer, a tumor of the brain, glioblastoma, sarcoma, a tumor of the bone, or Merkel cell carcinoma.

43 . The method of claim 32 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is administered to the patient by intravenous or subcutaneous administration.

44 . The method of claim 32 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof is pembrolizumab.

45 . The method of claim 32 , wherein the anti-PD-1 antibody and the anti-CTLA4 antibody are co-administered.

46 . The method of claim 32 , wherein the anti-PD-1 antibody and the anti-CTLA4 antibody are co-formulated.

47 . The method of claim 32 , comprising administering 25 mg of the anti-CTLA4 antibody or antigen binding fragment thereof.

48 . A kit for treating a patient with cancer, the kit comprising:

(a) about 400 mg of an anti-PD-1 antibody or antigen binding fragment thereof,

(b) about 25 mg, 50 mg, 75 mg, or 100 mg of an anti-CTLA4 antibody or antigen binding fragment thereof; and

(c) instructions for using the anti-PD-1 antibody or antigen binding fragment thereof and the anti-CTLA4 antibody or antigen binding fragment thereof, wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises:

i. light chain complementarity determining regions (CDRs) comprising a sequence of amino acids as set forth in SEQ ID NOs: 1, 2 and 3 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 6, 7 and 8; or

ii. light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 11, 12 and 13 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 14, 15 and 16;

and wherein the anti-CTLA4 antibody or antigen binding fragment thereof comprises:

i. light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 39, 40 and 41 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 36, 37, and 38;

ii. light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 39, 40 and 42 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 36, 37, and 38; or

iii. light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 39, 40 and 43 and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 36, 37, and 38.

49 . The kit of claim 48 , wherein the anti-PD-1 antibody is pembrolizumab.

50 . The kit of claim 48 , wherein the anti-CTLA4 antibody is a monoclonal antibody comprising light chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 39, 40, and 41, and heavy chain CDRs comprising a sequence of amino acids as set forth in SEQ ID NOs: 36, 37, and 38.

51 . The kit of claim 48 , wherein the anti-CTLA4 antibody is a monoclonal antibody comprising a heavy chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:50 and a light chain variable region comprising a sequence of amino acids as set forth in SEQ ID NO:49.

52 . The kit of claim 48 , wherein the anti-CTLA4 antibody is a monoclonal antibody comprising a heavy chain comprising a sequence of amino acids as set forth in SEQ ID NO:57 and a light chain comprising a sequence of amino acids as set forth in SEQ ID NO:58.

53 . The kit of claim 48 , comprising about 25 mg of the anti-CTLA4 antibody or antigen binding fragment thereof.