Methods of treating cancer using an Anti-ctla4 antibody and an enpp1 inhibitor
Patent Information
- Application Number
- HK62026127513
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-11-02
- Filing Date
- 2026-08-14
- Publication Date
- 2026-09-18
- Estimated Expiration
- 2044-04-11
Smart Images
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Abstract
Description
Methods for treating cancer using antibodies that specifically bind to human cytotoxic T-lymphocyte antigen 4 (CTLA-4) and an inhibitor of exonucleotide pyrophosphatase / phosphodiesterase family member 1 (ENPP1) are provided. Abstract
Claims
CLAIMS1. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of:(a) an antibody that specifically binds to human Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4); and(b) an ectonucleotide pyrophosphatase / phosphodiesterase family member 1 (ENPP1) inhibitor.
2. A method of enhancing the activation of T cells in a subject who has cancer, the method comprising administering to the subject a therapeutically effective amount of:(a) an antibody that specifically binds to human Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4); and(b) an ectonucleotide pyrophosphatase / phosphodiesterase family member 1 (ENPP1) inhibitor.
3. The method of claim 1 or 2, wherein the antibody comprises a human IgGi heavy chain constant region that is a variant of a wild-type human IgG heavy chain constant region, wherein the variant binds to FcyRIIIA with a higher affinity than the wild-type human IgGi heavy chain constant region binds to FcyRIIIA.
4. The method of any one of claims 1-3, wherein the antibody comprises: a heavy chain variable region (VH) comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 7; and a light chain variable region (VL) comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 8.
5. The method of any one of the preceding claims, wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences set forth in SEQ ID NOs: 1, 2, 3, 4, 5, and 6, respectively.
6. The method of any one of the preceding claims, wherein the antibody comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 7 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 8.
7. The method of any one of the preceding claims, wherein the antibody comprises a human IgGl heavy chain constant region comprising S239D / A330L / I332E mutations, numbered according to the EU numbering system.
8. The method of any one of the preceding claims, wherein the antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 9 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 10.
9. The method of any one of the preceding claims, wherein the antibody that specifically binds to human CTLA-4 is botensilimab.
10. The method of any one of the preceding claims, wherein the ENPP 1 inhibitor ispharmaceutically acceptable salt thereof.
11. The method of any one of the preceding claims, wherein the antibody is administered to the subject at a dose of 25 mg to 250 mg.
12. The method of any one of the preceding claims, wherein the antibody is administered to the subject at a dose of 25 mg, 50 mg, 75 mg, 100 mg, or 150 mg.
13. The method of any one of the preceding claims, wherein the antibody is administered to the subject intravenously, subcutaneously, or intratumorally.
14. The method of any one of claims 1-13, wherein the antibody is administered to the subject once weekly.
15. The method of any one of claims 1-13, wherein the antibody is administered to the subject once every 2 weeks.
16. The method of any one of claims 1-13, wherein the antibody is administered once every 3 weeks.
17. The method of any one of claims 1-13, wherein the antibody is administered to the subject once every 4 weeks.
18. The method of any one of claims 1-13, wherein the antibody is administered to the subject once every 5 weeks.
19. The method of any one of claims 1-13, wherein the antibody is administered to the subject once every 6 weeks.
20. The method of any one of claims 1-19, wherein the ENPP1 inhibitor is administered to the subject at a dose of 5 mg / day to 1000 mg / day.
21. The method of any one of claims 1-19, wherein the ENPP1 inhibitor is administered to the subject at a dose of 10 mg / day to 50 mg / day.
22. The method of any one of claims 1-19, wherein the ENPP1 inhibitor is administered to the subject at a dose of 10 mg / day, 20 mg / day, 30 mg / day, 40 mg / day, or 50 mg / day.
23. The method of any one of the preceding claims, wherein the cancer is bladder cancer, breast cancer, cervical cancer, colorectal cancer, colon adenocarcinoma, head and neck cancer, leukemia, lymphoma, tenosynovial giant cell tumor, gastric cancer, gastroesophageal cancer, glioblastoma, sarcoma, pancreatic cancer, melanoma, mesothelioma, renal cell adenocarcinoma, hepatocellular carcinoma, stomach adenocarcinoma, kidney renal clear cell carcinoma, esophageal carcinoma, ovarian cancer, small cell lung cancer, non-small cell lung cancer, or lung adenocarcinoma.
24. The method of any one of the preceding claims, wherein the cancer is relapsed and / or refractory.
25. The method of any one of the preceding claims, wherein the cancer is metastatic.
26. The method of any one of the preceding claims, wherein the cancer is microsatellite stable colorectal cancer.
27. The method of any one of claims 1-25, wherein the cancer is renal cell carcinoma.
28. The method of any one of claims 1-25, wherein the cancer is hepatocellular carcinoma.
29. The method of any one of claims 1-25, wherein the cancer is pancreatic cancer.
30. The method of any one of the preceding claims, wherein the subject has received at least one prior immunotherapy or chemotherapy.
31. The method of any one of claims 1-29, wherein the subject has not received any prior chemotherapy, radiotherapy, or immunotherapy.
32. The method of any one of claims 1-30, wherein the cancer is refractory to a standard of care treatment.
33. The method of claim 32, wherein the standard of care treatment is chemotherapy, immunotherapy, or radiation.
34. The method of any one of the preceding claims, wherein the method further comprises administering an additional therapeutic agent to the subject.
35. The method of claim 34, wherein the additional therapeutic agent is an antibody that specifically binds to human PD- 1.
36. The method of claim 35, wherein additional therapeutic agent is nivolumab, pembrolizumab, dostarlimab, or balstilimab.
37. The method of any one of the preceding claims, wherein the method reduces tumor size in the subject.
38. The method of any one of the preceding claims, wherein the method increases T-cell activation in the subject.
39. An antibody that specifically binds to human CTLA-4 and an ENPP 1 inhibitor for use in the treatment of cancer, wherein the treatment is performed according to the method of any one of the previous claims.
40. An antibody that specifically binds to human CTLA-4 and an ENPP 1 inhibitor for use in the manufacture of a medicament for the treatment of cancer, wherein the treatment is performed according to the method of any one of the previous claims.
41. Use of an antibody that specifically binds to human CTLA-4 and an ENPP 1 inhibitor for the treatment of cancer, wherein the treatment is performed according to the method of any one of the previous claims.
42. A therapeutic combination comprising:(a) an antibody that specifically binds to human Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4); and(b) an ectonucleotide pyrophosphatase / phosphodiesterase family member 1 (ENPP1) inhibitor.
43. The therapeutic combination of claim 42, wherein the antibody comprises a human IgGi heavy chain constant region that is a variant of a wild-type human IgG heavy chain constant region, wherein the variant binds to FcyRIIIA with a higher affinity than the wildtype human IgGi heavy chain constant region binds to FcyRIIIA.
44. The therapeutic combination of claim 42 or 43, wherein the antibody comprises: a heavy chain variable region (VH) comprising the CDRH1, CDRH2, and CDRH3 amino acid sequences of the VH amino acid sequence set forth in SEQ ID NO: 7; and a light chain variable region (VL) comprising the CDRL1, CDRL2, and CDRL3 amino acid sequences of the VL amino acid sequence set forth in SEQ ID NO: 8.
45. The therapeutic combination of any one of claims 42-44, wherein the antibody comprises the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences set forth in SEQ ID NOs: 1, 2, 3, 4, 5, and 6, respectively.
46. The therapeutic combination of any one of claims 42-45, wherein the antibody comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 7 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 8.
47. The therapeutic combination of any one of claims 42-46, wherein the antibody comprises a human IgGl heavy chain constant region comprising S239D / A330L / I332E mutations, numbered according to the EU numbering system.
48. The therapeutic combination of any one of claims 42-47, wherein the antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO: 9 and a light chain comprising the amino acid sequence set forth in SEQ ID NO: 10.
49. The therapeutic combination of any one of claims 42-48, wherein the antibody is botensilimab.
50. The therapeutic combination of any one of claims 42-49, wherein the ENPP1 inhibitor ispharmaceutically acceptable salt thereof.