COMBINATON THERAPY WITH A DON PRODRUG AND AN IMMUNE CHECKPOINT INHIBITOR

1 . A method of treating a subject having cancer, the method comprising administering to the subject in need thereof a therapeutically effective amount of:

(a) isopropyl (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt or solvate thereof; or

(b) isopropyl (S)-2-((S)-6-acetamido-2-((3S,5S,7S)-adamantane-1-carboxamido) hexanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt thereof;

(c) (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoic acid, or a pharmaceutically acceptable salt thereof; or

(d) 6-diazo-5-oxo-L-norleucine; and

(e) an immune checkpoint inhibitor,

wherein the isopropyl (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt or solvate thereof, or

isopropyl (S)-2-((S)-6-acetamido-2-((3S,5S,7S)-adamantane-1-carboxamido) hexanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt thereof, or

(S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoic acid, or a pharmaceutically acceptable salt thereof, or

6-diazo-5-oxo-L-norleucine, or a pharmaceutically acceptable salt thereof, is administered to the subject according to an intermittent dosing schedule,

and wherein the immune checkpoint inhibitor is selected from the group consisting of an anti-PD-1 antibody, an anti-PD-L1 antibody, an anti-CTLA-4 antibody, an anti-LAG3 antibody, and an anti-TIM3 antibody.

2 - 4 . (canceled)

5 . The method of claim 1 , wherein the anti-PD-1 antibody is selected from the group consisting of nivolumab, pembrolizumab, pidilizumab, STI-A1110, PDR001, MEDI 0680, AGEN2034, BGB-A317, AB122, TSR-042, PF-06801591, cemiplimab, SYM021, JNJ 63723283, HLX10, LZM009, and MGA012.

6 . (canceled)

7 . (canceled)

8 . The method of claim 1 , wherein the anti-PD-L1 antibody is selected from the group consisting of avelumab, atezolizumab, durvalumab, and STI-A1014.

9 . (canceled)

10 . (canceled)

11 . The method of claim 1 , wherein the anti-CTLA-4 antibody is selected from the group consisting of ipilimumab and tremelimumab.

12 . (canceled)

13 . (canceled)

14 . The method of claim 1 , wherein the anti-LAG3 antibody is GSK2831781.

15 . (canceled)

16 . The method of claim 15 , wherein the TIM3 inhibitor is an anti-TIM3 antibody.

17 . The method of claim 1 , wherein the cancer is or has become resistant to treatment with at least one immune checkpoint inhibitor.

18 - 21 . (canceled)

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

23 . The method of claim 1 , wherein the cancer is a hematological cancer.

24 . (canceled)

25 . The method of claim 1 , wherein the cancer is selected from the group consisting of hepatocellular carcinoma, glioblastoma, lung cancer, breast cancer, head and neck cancer, prostate cancer, melanoma, and colorectal cancer.

26 . (canceled)

27 . The method of claim 1 , wherein isopropyl (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt or solvate thereof, or isopropyl (S)-2-((S)-6-acetamido-2-((3S,5S,7S)-adamantane-1-carboxamido)hexanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt thereof, or (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoic acid, or a pharmaceutically acceptable salt thereof, or 6-diazo-5-oxo-L-norleucine is administered to the subject three times a week on non-consecutive days.

28 - 32 . (canceled)

33 . A method of treating a subject having cancer, the method comprising administering to the subject in need thereof a therapeutically effective amount of isopropyl (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt or solvate thereof, or isopropyl (S)-2-((S)-6-acetamido-2-((3S,5S,7S)-adamantane-1-carboxamido)hexanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt thereof, or (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoic acid, or a pharmaceutically acceptable salt thereof, according to an intermittent dosing schedule.

34 . The method of claim 33 , wherein the cancer is a solid tumor.

35 . The method of claim 33 , wherein the cancer is a hematological cancer.

36 . (canceled)

37 . The method of claim 33 , wherein the cancer is selected from the group consisting of hepatocellular carcinoma, glioblastoma, lung cancer, breast cancer, head and neck cancer, prostate cancer, melanoma, and colorectal cancer.

38 . (canceled)

39 . The method of claim 33 , wherein isopropyl (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt or solvate thereof, or isopropyl (S)-2-((S)-6-acetamido-2-((3S,5S,7S)-adamantane-1-carboxamido)hexanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt thereof, or (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoic acid, or a pharmaceutically acceptable salt thereof, is administered to the subject three times a week on non-consecutive days.

40 - 43 . (canceled)

44 . The method of claim 1 , wherein isopropyl (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoate, or a pharmaceutically acceptable salt or solvate thereof, is administered to the subject.

45 . (canceled)

46 . The method of claim 1 , wherein (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoic acid, or a pharmaceutically acceptable salt thereof, is administered to the subject.

47 . A method of treating a subject having cancer, the method comprising administering to the subject in need thereof a therapeutically effective amount of 6-diazo-5-oxo-L-norleucine for 5 consecutive days in a row followed by 2 consecutive days in a row wherein 6 diazo-5-oxo-L-norleucine is not administered.

48 - 55 . (canceled)

56 . (S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)propanamido)-6-diazo-5-oxohexanoic acid, or a pharmaceutically acceptable salt thereof.

57 . A pharmaceutical composition comprising the compound of claim 56 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.