Dosage and administration of non-fucosylated anti-CD40 antibodies

1. A method of treating cancer, the method comprising administering an anti-CTLA-4 antibody and a composition comprising an anti-CD40 antibody to a patient in need thereof, wherein the anti-CTLA-4 antibody is selected from the group consisting of ipilimumab and tremelimumab,

wherein the anti-CD40 antibody comprises a heavy chain variable region comprising amino acids 1-113 of SEQ ID NO:1 and a light chain variable region comprising amino acids 1-113 of SEQ ID NO:2, and a human constant region; wherein the constant region has an N-glycoside-linked sugar chain at residue N297 according to the EU index; and wherein less than 5% of N-glycoside-linked sugar chains in the composition comprise a fucose residue; and wherein the anti-CD40 antibody is administered at a dose level between 2-50 μg/kg (μg per kilogram of patient body weight).

2. A method of treating cancer, the method comprising administering an anti-PD-L1 antibody and a composition comprising an anti-CD40 antibody to a patient in need thereof, wherein the anti-PD-L1 antibody is selected from the group consisting of durvalumab (MEDI4736) and atezolizumab (MPDL3280A),

wherein the anti-CD40 antibody comprises a heavy chain variable region comprising amino acids 1-113 of SEQ ID NO:1 and a light chain variable region comprising amino acids 1-113 of SEQ ID NO:2, and a human constant region; wherein the constant region has an N-glycoside-linked sugar chain at residue N297 according to the EU index; and wherein less than 5% of N-glycoside-linked sugar chains in the composition comprise a fucose residue; and wherein the anti-CD40 antibody is administered at a dose level between 2-50 μg/kg (μg per kilogram of patient body weight).

3. The method of claim 1 , wherein the cancer is a hematologic cancer.

4. The method of claim 1 , wherein the cancer is a solid tumor.

5. The method of claim 2 , wherein the cancer is a hematologic cancer.

6. The method of claim 2 , wherein the cancer is a solid tumor.

7. The method of claim 1 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

8. The method of claim 1 , wherein the anti-CD40 antibody is administered at a dose level of 30 μg/kg.

9. The method of claim 1 , further comprising administering one or more chemotherapeutic agents to the patient.

10. The method of claim 9 , wherein the one or more chemotherapeutic agents comprise gemcitabine, paclitaxel, or both.

11. The method of claim 2 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

12. The method of claim 2 , wherein the anti-CD40 antibody is administered at a dose level of 30 μg/kg.

13. The method of claim 1 , further comprising administering one or more chemotherapeutic agents to the patient.

14. The method of claim 13 , wherein the one or more chemotherapeutic agents comprise gemcitabine, paclitaxel, or both.

15. The method of claim 1 , wherein the cancer is selected from the group consisting of melanoma, breast cancer, metastatic breast cancer, lung cancer, non-small cell lung cancer, bladder cancer, pancreatic cancer, B-cell lymphoma, Hodgkin lymphoma, diffuse large cell B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, small cell lung cancer, ovarian cancer, kidney cancer, cervical cancer, head and neck cancer, prostate cancer, glioblastoma, non-Hodgkin lymphoma, hepatocellular carcinoma, and multiple myeloma.

16. The method of claim 15 , wherein the cancer is pancreatic cancer, melanoma, non-small cell lung cancer, or head and neck cancer.

17. The method of claim 1 , wherein the patient has a CD40 positive cancer.

18. The method of claim 1 , wherein the patient has a CD40 negative cancer.

19. The method of claim 2 , wherein the cancer is selected from the group consisting of melanoma, breast cancer, metastatic breast cancer, lung cancer, non-small cell lung cancer, bladder cancer, pancreatic cancer, B-cell lymphoma, Hodgkin lymphoma, diffuse large cell B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, small cell lung cancer, ovarian cancer, kidney cancer, cervical cancer, head and neck cancer, prostate cancer, glioblastoma, non-Hodgkin lymphoma, hepatocellular carcinoma, and multiple myeloma.

20. The method of claim 19 , wherein the cancer is pancreatic cancer, melanoma, non-small cell lung cancer, or head and neck cancer.

21. The method of claim 2 , wherein the patient has a CD40 positive cancer.

22. The method of claim 2 , wherein the patient has a CD40 negative cancer.

23. The method of claim 9 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

24. The method of claim 23 , wherein the cancer is selected from the group consisting of melanoma, breast cancer, metastatic breast cancer, lung cancer, non-small cell lung cancer, bladder cancer, pancreatic cancer, B-cell lymphoma, Hodgkin lymphoma, diffuse large cell B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, small cell lung cancer, ovarian cancer, kidney cancer, cervical cancer, head and neck cancer, prostate cancer, glioblastoma, non-Hodgkin lymphoma, hepatocellular carcinoma, and multiple myeloma.

25. The method of claim 24 , wherein the cancer is pancreatic cancer, melanoma, non-small cell lung cancer, or head and neck cancer.

26. The method of claim 25 , wherein the cancer is pancreatic cancer.

27. The method of claim 10 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

28. The method of claim 16 , wherein the cancer is pancreatic cancer.

29. The method of claim 16 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg or 30 μg/kg.

30. The method of claim 29 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

31. The method of claim 1 , wherein the anti-CD40 antibody is administered at least once every three weeks.

32. The method of claim 31 , wherein the anti-CD40 antibody is administered on day one of a three week cycle.

33. The method of claim 1 , wherein the anti-CD40 antibody is administered intravenously or subcutaneously to the patient.

34. The method of claim 13 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

35. The method of claim 34 , wherein the cancer is selected from the group consisting of melanoma, breast cancer, metastatic breast cancer, lung cancer, non-small cell lung cancer, bladder cancer, pancreatic cancer, B-cell lymphoma, Hodgkin lymphoma, diffuse large cell B-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, small cell lung cancer, ovarian cancer, kidney cancer, cervical cancer, head and neck cancer, prostate cancer, glioblastoma, non-Hodgkin lymphoma, hepatocellular carcinoma, and multiple myeloma.

36. The method of claim 35 , wherein the cancer is pancreatic cancer, melanoma, non-small cell lung cancer, or head and neck cancer.

37. The method of claim 36 , wherein the cancer is pancreatic cancer.

38. The method of claim 14 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

39. The method of claim 20 , wherein the cancer is pancreatic cancer.

40. The method of claim 20 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg or 30 μg/kg.

41. The method of claim 40 , wherein the anti-CD40 antibody is administered at a dose level of 10 μg/kg.

42. The method of claim 2 , wherein the anti-CD40 antibody is administered at least once every three weeks.

43. The method of claim 42 , wherein the anti-CD40 antibody is administered on day one of a three week cycle.

44. The method of claim 2 , wherein the anti-CD40 antibody is administered intravenously or subcutaneously to the patient.

45. The method of claim 1 , wherein the anti-CD40 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2.

46. The method of claim 2 , wherein the anti-CD40 antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2.