Use of combination of anti-PD-1 antibody and VEGFR inhibitor in preparation of drug for treating cancers

Patent metadata

Field	Value
Publication number	US-12435144-B2
Application number	US-202318517345-A
Country	US
Kind code	B2
Filing date	Nov 22, 2023
Priority date	Oct 10, 2016
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

Disclosed is the use of a combination of an anti-PD-1 antibody and a VEGFR inhibitor in the preparation of a drug for treating cancers.

First claim

We claim:

1. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject, an anti-PD-1 antibody and apatinib having the structure of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein the anti-PD-1 antibody comprises:
an antibody light chain variable region comprising LCDR1, LCDR2 and LCDR3 having the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively; and
an antibody heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively,
wherein the anti-PD-1 antibody blocks the PD-1/PD-L1 signaling pathway;
and the apatinib inhibits the activity of VEGFR-2.

2. The method of claim 1 , comprising administering to the subject a pharmaceutically acceptable salt of apatinib selected from the group consisting of mesylate salt of apatinib and hydrochloride salt of apatinib.

3. The method of claim 1 , wherein the anti-PD-1 antibody is a humanized antibody.

4. The method of claim 3 , wherein the humanized antibody comprises an antibody light chain variable region having the amino acid sequence of SEQ ID NO: 8 or a mutant sequence thereof, and an antibody heavy chain variable region having the amino acid sequence of SEQ ID NO: 7 or a mutant sequence thereof, wherein the mutant sequence has 1 to 10 amino acid substitution(s) in SEQ ID NO: 8 or SEQ ID NO: 7, respectively.

5. The method of claim 4 , wherein the antibody light chain variable region comprises the amino acid sequence of SEQ ID NO: 8 and the antibody heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 7.

6. The method of claim 4 , wherein the antibody light chain variable region comprises a mutant sequence of the amino acid sequence of SEQ ID NO: 8 having the amino acid substitution A43S, and the antibody heavy chain variable region comprises a mutant sequence of the amino acid sequence of SEQ ID NO: 7 having the amino acid substitution G44R.

7. The method of claim 1 , wherein the cancer is selected from the group consisting of breast cancer, lung cancer, liver cancer, gastric cancer, intestinal cancer, renal cancer, melanoma and non-small cell lung cancer.

8. The method of claim 7 , wherein the subject has failed at least one chemotherapy prior to the administration of the anti-PD-1 antibody and apatinib or the pharmaceutically acceptable salt thereof.

9. The method of claim 1 , wherein the anti-PD-1 antibody is administered at a dose of 2 mg/kg to 6 mg/kg or from 100 mg to 1000 mg per administration.

10. The method of claim 1 , wherein the anti-PD-1 antibody is administered at a dose of 3 mg/kg body weight of the subject or 200 mg once every two weeks.

11. The method of claim 1 , wherein the apatinib or the pharmaceutically acceptable salt thereof is administered orally at a dose from 100 mg to 500 mg.

12. The method of claim 1 , wherein the apatinib or the pharmaceutically acceptable salt thereof is administered orally at a dose of 125 mg, 250 mg, 375 mg, 500 mg, or any dosage in between, once daily.

13. A pharmaceutical kit comprising apatinib or a pharmaceutically acceptable salt thereof and an anti-PD-1 antibody, wherein the anti-PD-1 antibody comprises:
an antibody light chain variable region comprising LCDR1, LCDR2 and LCDR3 having the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively; and
an antibody heavy chain variable region comprising HCDR1, HCDR2 and HCDR3 having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively.

14. The kit of claim 13 , comprising mesylate salt of apatinib and the anti-PD-1 antibody, wherein the anti-PD-1 antibody comprises an antibody light chain variable region comprising the amino acid sequence of SEQ ID NO: 8 and an antibody heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7.

15. The method of claim 1 , wherein the administration of the anti-PD-1 antibody, and apatinib or a pharmaceutically acceptable salt thereof reduces an adverse effect of an anti-PD-1 antibody, or apatinib or a pharmaceutically acceptable salt thereof, wherein the adverse effect is selected from hemangiomas, hypothyroidism, pruritus and diarrhea.

16. The method of claim 1 , wherein the administration of the anti-PD-1 antibody, and apatinib or a pharmaceutically acceptable salt thereof has a better anti-tumor effect than the administration of the anti-PD-1 antibody, or the administration of the apatinib or a pharmaceutically acceptable salt thereof alone.

17. The method of claim 1 , wherein the administration of the anti-PD-1 antibody, and apatinib or a pharmaceutically acceptable salt thereof has a synergistic anti-tumor effect compared to the administration of the anti-PD-1 antibody, and the administration of the apatinib or a pharmaceutically acceptable salt thereof.

18. The method of claim 1 , wherein the cancer is a cancer expressing PD-L1.

19. The method of claim 1 , wherein the subject is a human subject.

Assignees

• Suzhou Suncadia Biopharmaceuticals Co Ltd
• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Sun Xing
• Cao Guoqing
• Yang Changyong
• Zhang Lianshan
• Guo Yong

Classifications

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K2039/505

  comprising antibodies · CPC title