IP Library › Patent Application 17921521

Patent Application

App. No. 17/921,521

Anti-CD40 Antibody Combination Treatment for Cancer

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Patent No.: US None
App. No.: 17/921,521

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Abstract

This disclosure relates to methods of treating cancer using a combination of an anti-CD40 antibody such as SEA-CD40, and an anti-PD-1 antibody such as pembrolizumab. The treatment can further include a chemotherapy.

Claims (231)

1 . A method of treating a pancreatic cancer comprising administering to a patient having the pancreatic cancer:

(i) a chemotherapy on day 1, day 8, and day 15 of each 28-day cycle,

(ii) a composition comprising an anti-CD40 antibody on day 3 of each 28-day cycle, and

(iii) an anti-PD-1 antibody on day 8 of each 42-day cycle;

wherein the anti-CD40 antibody: 1) comprises a heavy chain variable region comprising amino acid 1-113 of SEQ ID NO: 1 and a light chain variable region comprising amino acid 1-113 of SEQ ID NO: 2, and a human constant region; wherein the human constant region has an N-glycoside-linked sugar chain at residue N297 according to the EU index; and wherein less than 20% of N-glycoside-linked sugar chains in the composition comprise a fucose residue; and/or 2) is a SEA-CD40 variant; and

wherein the anti-PD-1 antibody comprises a light chain comprising CDRs of SEQ ID NOs: 3-5, and a heavy chain comprising CDRs of SEQ ID NOs 8-10.

2 . The method of claim 1 wherein less than 10% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

3 . The method of claim 1 or 2 wherein less than 5% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

4 . The method of any one of claims 1-3 wherein less than 3% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

5 . The method of any one of claims 1-4 wherein less than 2% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

6 . The method of any one of claims 1-5 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.

7 . The method of any one of claims 1-6 , where in the anti-CD40 antibody is SEA-CD40.

8 . The method of any one of claims 1-5 wherein the anti-CD40 antibody is a SEA-CD40 variant.

9 . The method of any one of claims 1-8 wherein the light chain of the anti-PD-1 antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6, and wherein the heavy chain of the anti-PD-1 antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

10 . The method of any one of claims 1-9 wherein the light chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 7, and wherein the heavy chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 12.

11 . The method of any one of claims 1-10 wherein the anti-PD-1 antibody is pembrolizumab.

12 . The method of any one of claims 1-9 wherein the anti-PD-1 antibody is a pembrolizumab variant.

13 . The method of any one of claims 1-12 wherein the chemotherapy comprises gemcitabine and/or paclitaxel.

14 . The method of claim 13 wherein paclitaxel is nab-paclitaxel.

15 . The method of any one of claims 1-14 wherein the anti-CD40 antibody is administered at 10 µg/kg.

16 . The method of any one of claims 1-14 wherein the anti-CD40 antibody is administered at 30 µg/kg.

17 . The method of any one of claims 1-16 wherein the anti-PD-1 antibody is administered at 400 mg.

18 . The method of any one of claims 1-17 wherein the anti-PD-1 antibody is administered intravenously.

19 . The method of any one of claims 1-18 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC).

20 . The method of any one of claims 1-19 , wherein the anti-CD40 antibody is administered intravenously.

21 . The method of any one of claims 1-19 , wherein the anti-CD40 antibody is administered subcutaneously.

22 . A method of treating a cancer comprising:

(i) administering a chemotherapy to a patient having the cancer in a cycle of every 4 weeks,

(ii) administering a composition comprising an anti-CD40 antibody to the patient in a cycle of every 4 weeks, and

(iii) administering an anti-PD-1 antibody to the patient in a cycle of every 3 weeks or 6 weeks,

wherein the chemotherapy is administered on day 1, day 8, day 15 of each 4-week cycle, the anti-CD40 antibody is administered on day 3 of each 4-week cycle, and the anti-PD-1 antibody is administered on day 8 of each of the 3-week cycle or 6-week cycle;

wherein the anti-PD-1 antibody comprises a light chain comprising CDRs of SEQ ID NOs: 3-5, and a heavy chain comprising CDRs of SEQ ID NOs 8-10.

23 . The method of claim 22 wherein less than 10% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

24 . The method of claim 22 or 23 wherein less than 5% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

25 . The method of any one of claims 22-24 wherein less than 3% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

26 . The method of any one of claims 22-25 wherein less than 2% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

27 . The method of any one of claims 22-26 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.

28 . The method of any one of claims 22-27 , where in the anti-CD40 antibody is SEA-CD40.

29 . The method of any one of claims 22-26 wherein the anti-CD40 antibody is a SEA-CD40 variant.

30 . The method of any one of claims 22-29 wherein the light chain of the anti-PD-1 antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6, and wherein the heavy chain of the anti-PD-1 antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

31 . The method of any one of claims 22-30 wherein the light chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 7, and wherein the heavy chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 12.

32 . The method of any one of claims 22-31 wherein the anti-PD-1 antibody is pembrolizumab.

33 . The method of any one of claims 22-30 wherein the anti-PD-1 antibody is a pembrolizumab variant.

34 . The method of any one of claims 22-33 , wherein the anti-PD-1 antibody is administered in a cycle of every 3 weeks, and the anti-PD-1 antibody is administered on day 8 of each 3-week cycle at a dose of 200 mg.

35 . The method of any one of claims 22-33 , wherein the anti-PD-1 antibody is administered in a cycle of every 6 weeks, and the anti-PD-1 antibody is administered on day 8 of each 6-week cycle at a dose of 400 mg.

36 . The method of any one of claims 22-35 wherein the anti-PD-1 antibody is administered intravenously.

37 . A method of treating a cancer comprising:

(i) administering an anti-CD40 antibody to a patient having the cancer in a cycle of every week, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, or every 8 weeks, wherein the cycle comprises a first cycle of administration of the anti-CD40 antibody,

(ii) administering an anti-PD-1 antibody to the patient in a cycle of every 3 weeks or every 6 weeks, wherein the cycle comprises a first cycle of administration of the anti-PD-1 antibody,

wherein a first administration of the anti-CD40 antibody in the first cycle of administration of the anti-CD40 antibody is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days prior to a first administration of the anti-PD-1 antibody in the first cycle of administration of the anti-PD-1 antibody;

wherein the anti-PD-1 antibody comprises a light chain comprising CDRs of SEQ ID NOs: 3-5, and a heavy chain comprising CDRs of SEQ ID NOs 8-10.

38 . The method of claim 37 wherein less than 10% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

39 . The method of claim 37 or 38 wherein less than 5% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

40 . The method of any one of claims 37-39 wherein less than 3% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

41 . The method of any one of claims 37-40 wherein less than 2% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

42 . The method of any one of claims 37-41 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.

43 . The method of any one of claims 37-42 , where in the anti-CD40 antibody is SEA-CD40.

44 . The method of any one of claims 37-41 wherein the anti-CD40 antibody is a SEA-CD40 variant.

45 . The method of any one of claims 37-44 wherein the light chain of the anti-PD-1 antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6, and wherein the heavy chain of the anti-PD-1 antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

46 . The method of any one of claims 37-45 wherein the light chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 7, and wherein the heavy chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 12.

47 . The method of any one of claims 37-46 wherein the anti-PD-1 antibody is pembrolizumab.

48 . The method of any one of claims 37-45 wherein the anti-PD-1 antibody is a pembrolizumab variant.

49 . The method of any one of claims 37-48 , wherein the anti-CD40 antibody is administered in a cycle of every 2 weeks, every 4 weeks, every 6 weeks, or every 8 weeks.

50 . The method of any one of claims 37-49 , wherein the anti-CD40 antibody is administered in a cycle of every 4 weeks or every 8 weeks.

51 . The method of any one of claims 37-50 , wherein the anti-CD40 antibody is administered in a cycle of every 4 weeks.

52 . The method of any one of claims 37-51 , wherein the anti-PD-1 antibody is administered in a cycle of every 3 weeks at a dose of 200 mg.

53 . The method of any one of claims 37-51 , wherein the anti-PD-1 antibody is administered in a cycle of every 6 weeks at a dose of 400 mg.

54 . The method of any one of claims 37-53 wherein the anti-PD-1 antibody is administered intravenously.

55 . The method of any one of claims 37-54 , wherein the first administration of the anti-CD40 antibody in the first cycle is 2 days, 3 days, 4 days, 5 days, or 6 days prior to the first administration of the anti-PD-1 antibody in the first cycle.

56 . The method of any one of claims 37-55 , wherein the first administration of the anti-CD40 antibody in the first cycle is 3 days, 4 days, or 5 days prior to the first administration of the anti-PD-1 antibody in the first cycle.

57 . The method of any one of claims 37-56 , wherein the first administration of the anti-CD40 antibody in the first cycle is 5 days prior to the first administration of the anti-PD-1 antibody in the first cycle.

58 . The method of any one of claims 37-48 , wherein the anti-CD40 antibody and the anti-PD-1 antibody are administered in their first cycles according to a treatment regimen selected from the group consisting of:

the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 2;

the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 3;

the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 4;

the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 5;

the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 6;

the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 7;

the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 8;

the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 3;

the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 4;

the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 5;

the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 6;

the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 7;

the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 8;

the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 4;

the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 5;

the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 6;

the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 7;

the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 8;

the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 5;

the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 6;

the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 7;

the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 8;

the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 6;

the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 7;

the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 8;

the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 7;

the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 8; and

the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 8.

59 . The method of claim 58 , wherein the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 3.

60 . The method of claim 58 , wherein the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 5.

61 . The method of claim 58 , wherein the anti-CD40 antibody is first administered on day 1, and the anti-PD-1 antibody is first administered on day 8.

62 . The method of claim 58 , wherein the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 5.

63 . The method of claim 58 , wherein the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 8.

64 . The method of claim 58 , wherein the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 8.

65 . A method of treating a cancer comprising:

(i) administering a chemotherapy to a patient having the cancer in a cycle of every 3 weeks, every 4 weeks, every 5 weeks, or every 6 weeks,

(ii) administering an anti-CD40 antibody to a patient having the cancer in a cycle of every week, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, or every 8 weeks, and

(iii) administering an anti-PD-1 antibody to the patient in a cycle of every 3 weeks or every 6 weeks,

wherein a first administration of the chemotherapy in the first cycle of administration of the chemotherapy is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days prior to a first administration of the anti-CD40 antibody in the first cycle of administration of the anti-CD40 antibody,

wherein a first administration of the anti-CD40 antibody in the first cycle of administration of the anti-CD40 antibody is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days prior to the first administration of the anti-PD-1 antibody in the first cycle of administration of the anti-PD-1 antibody;

wherein the anti-PD-1 antibody comprises a light chain comprising CDRs of SEQ ID NOs: 3-5, and a heavy chain comprising CDRs of SEQ ID NOs 8-10.

66 . The method of claim 65 wherein less than 10% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

67 . The method of claim 65 or 66 wherein less than 5% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

68 . The method of any one of claims 65-67 wherein less than 3% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

69 . The method of any one of claims 65-68 wherein less than 2% of N-glycoside-linked sugar chains in the composition comprise a fucose residue.

70 . The method of any one of claims 65-69 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.

71 . The method of any one of claims 65-70 , where in the anti-CD40 antibody is SEA-CD40.

72 . The method of any one of claims 65-69 wherein the anti-CD40 antibody is a SEA-CD40 variant.

73 . The method of any one of claims 65-72 wherein the light chain of the anti-PD-1 antibody has a light chain variable region comprising the amino acid sequence of SEQ ID NO: 6, and wherein the heavy chain of the anti-PD-1 antibody has a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 11.

74 . The method of any one of claims 65-73 wherein the light chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 7, and wherein the heavy chain of the anti-PD-1 antibody comprises the amino acid sequence of SEQ ID NO: 12.

75 . The method of any one of claims 65-74 wherein the anti-PD-1 antibody is pembrolizumab.

76 . The method of any one of claims 65-73 wherein the anti-PD-1 antibody is a pembrolizumab variant.

77 . The method of any one of claims 65-76 , wherein the chemotherapy comprises one or both of gemcitabine and paclitaxel.

78 . The method of any one of claims 65-77 , wherein the chemotherapy comprises both gemcitabine and paclitaxel.

79 . The method of any one of claims 65-78 , wherein the chemotherapy consists of gemcitabine and paclitaxel.

80 . The method of any one of claims 77-79 , wherein paclitaxel is nab-paclitaxel.

81 . The method of any one of claims 77-79 , wherein paclitaxel is albumin-bound paclitaxel.

82 . The method of any one of claims 65-81 , wherein the anti-CD40 antibody is administered in a cycle of every 2 weeks, every 4 weeks, every 6 weeks, or every 8 weeks.

83 . The method of any one of claims 65-82 , wherein the anti-CD40 antibody is administered in a cycle of every 4 weeks or every 8 weeks.

84 . The method of any one of claims 65-83 , wherein the anti-CD40 antibody is administered in a cycle of every 4 weeks.

85 . The method of any one of claims 65-84 , wherein the anti-PD-1 antibody is administered in a cycle of every 3 weeks at a dose of 200 mg.

86 . The method of any one of claims 65-85 , wherein the anti-PD-1 antibody is administered in a cycle of every 6 weeks at a dose of 400 mg.

87 . The method of any one of claims 65-86 wherein the anti-PD-1 antibody is administered intravenously.

88 . The method of any one of claims 65-87 , wherein the first administration of the chemotherapy in the first cycle is 2 days, 3 days, 4 days, 5 days, or 6 days prior to the first administration of the anti-CD40 antibody in the first cycle, and

wherein the first administration of the anti-CD40 antibody in the first cycle is 2 days, 3 days, 4 days, 5 days, or 6 days prior to the first administration of the anti-PD-1 antibody in the first cycle.

89 . The method of any one of claims 65-88 , wherein the first administration of the chemotherapy in the first cycle is 2 days, 3 days, or 4 days prior to the first administration of the anti-CD40 antibody in the first cycle, and

wherein the first administration of the anti-CD40 antibody in the first cycle is 3 days, 4 days, or 5 days prior to the first administration of the anti-PD-1 antibody in the first cycle.

90 . The method of any one of claims 33-45 , where the first administration of the chemotherapy in the first cycle is 2 days prior to the first administration of the anti-CD40 antibody in the first cycle, and

wherein the first administration of the anti-CD40 antibody in the first cycle is 5 days prior to the first administration of the anti-PD-1 antibody in the first cycle.

91 . The method of any one of claims 65-87 , wherein the chemotherapy, the anti-CD40 antibody and the anti-PD-1 antibody are administered in their first cycles according to a treatment regimen selected from the group consisting of:

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 3;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 4;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 5;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 6;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 7;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 8;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 9;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 10;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 11;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 12;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 13;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 14;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 2, and the anti-PD-1 antibody is first administered on day 15;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 4;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 5;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 6;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 7;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 8;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 9;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 10;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 11;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 12;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 13;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 14;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 15;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 5;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 6;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 7;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 8;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 9;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 10;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 11;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 12;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 13;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 14;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 4, and the anti-PD-1 antibody is first administered on day 15;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 6;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 7;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 8;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 9;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 10;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 11;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 12;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 13;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 14;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 15;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 7;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 8;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 9;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 10;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 11;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 13;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 14;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 6, and the anti-PD-1 antibody is first administered on day 15;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 8;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 9;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 10;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 11;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 12;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 13;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 14;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 15;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 9;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 10;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 11;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 12;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 13;

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 14; and

the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 15.

92 . The method of claim 91 wherein the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 3, and the anti-PD-1 antibody is first administered on day 8.

93 . The method of claim 91 wherein the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 5, and the anti-PD-1 antibody is first administered on day 8.

94 . The method of claim 91 wherein the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 8.

95 . The method of claim 91 wherein the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 7, and the anti-PD-1 antibody is first administered on day 15.

96 . The method of claim 91 wherein the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 10, day 11, day 12, or day 15.

97 . The method of claim 91 wherein the chemotherapy is first administered on day 1, the anti-CD40 antibody is first administered on day 8, and the anti-PD-1 antibody is first administered on day 15.

98 . The method of any one of claims 65-97 , wherein the chemotherapy is administered in a cycle of every 4 weeks.

99 . The method of any one of claims 65-97 , wherein the chemotherapy is administered on day 1, day 5, and day 8 of each cycle.

100 . The method of any one of claims 65-99 , wherein the anti-CD40 antibody is administered in a cycle of every 4 weeks.

101 . The method of any one of claims 22-100 , wherein the anti-CD40 antibody is administered at a dose of about 3 µg/kg, about 10 µg/kg, about 30 µg/kg, about 45 µg/kg, or about 60 µg/kg patient body weight.

102 . The method of claim 101 , wherein the anti-CD40 antibody is administered at a dose of about 10 µg/kg patient body weight.

103 . The method of claim 101 , wherein the anti-CD40 antibody is administered at a dose of about 30 µg/kg patient body weight.

104 . The method of any one of claims 22-103 , wherein the cancer is melanoma; breast cancer, metastatic breast cancer; lung cancer, non-small cell lung cancer (NSCLC), or pancreatic cancer.

105 . The method of any one of claims 22-104 , wherein the cancer is pancreatic cancer.

106 . The method of any one of claims 22-105 , wherein the cancer is pancreatic ductal adenocarcinoma (PDAC).

107 . The method of any one of claims 22-106 , wherein the cancer is metastatic pancreatic ductal adenocarcinoma.