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-11208484-B2
Application number	US-201716339819-A
Country	US
Kind code	B2
Filing date	Oct 9, 2017
Priority date	Oct 10, 2016
Publication date	Dec 28, 2021
Grant date	Dec 28, 2021

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 reducing an adverse effect of an anti-PD-1 antibody in a subject in need of a treatment of a cancer, the method comprising administering to the subject, an anti-PD-1 antibody and apatinib or the pharmaceutically acceptable salt thereof, wherein the adverse effect comprises at least hemangiomas, and 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.

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 and an antibody heavy chain variable region having the amino acid sequence of SEQ ID NO:7.

5. The method of claim 3 , wherein the humanized antibody comprises an antibody light chain variable region comprising a mutant sequence of the amino acid sequence of SEQ ID NO:8 having the amino acid substitution A43S, and an antibody heavy chain variable region comprising a mutant sequence of the amino acid sequence of SEQ ID NO: 7 having the amino acid substitution G44R.

6. 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.

7. The method of claim 6 , 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.

8. 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, and the apatinib or the pharmaceutically acceptable salt thereof is administered orally at a dose from 100 mg to 500 mg.

9. 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, and apatinib or the pharmaceutically acceptable salt thereof is administered orally at a dose of 125 mg, 250 mg, 375 mg, or any dosage in between, once daily.

Assignees

• Suzhou Suncadia Biopharmaceuticals Co Ltd
• Jiangsu Hengrui Medicine Co

Inventors

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

Classifications

• A61K31/444

  containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone · CPC title

• C07K16/2818 Primary

  against CD28 or CD152 · CPC title

• A61K2039/86

  Lung · CPC title

• A61K2039/545

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

• A61K2039/505

  comprising antibodies · CPC title