Use of an anti-PD-1 antibody combined with a vegfr inhibitor in the preparation of a drug for treating cancer

A PD-1, inhibitor technology, applied in the direction of antibody medical components, antibodies, drug combinations, etc., can solve problems such as poor inhibitory effect, burden on mental health and quality of life, and no inhibitory effect

Active Publication Date: 2019-11-12
SUZHOU SUNCADIA BIOPHARM CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these VEGFR inhibitors, including sorafenib, sunitinib, axitinib, and pazopanib, have different mechanisms of action from apatinib, which has the strongest effect on VEGFR-2. Inhibitory effect, but for other kinases, the inhibitory effect is poor or has no inhibitory effect at all, that is, apatinib is highly selective for VEGFR-2, so the disease it treats is also different from the aforementioned drugs, which is different from PD Whether the -1 combination can produce a synergistic effect, thereby improving the curative effect is worthy of further study; in addition, according to the current clinical research on PD-1 administered alone (PhaseI study of the anti-PD-1 antibody SHR-1210 in patients with advanced solidtumors.( 2017): e15572-e15572), when PD-1 antibody was used alone, the incidence of capillary hemangioma was as high as 79.3%, the incidence of hypothyroidism was 29.3%, the incidence of pruritus was 19.0%, and the incidence of diarrhea was 10.3%. Such a high incidence of adverse reactions will undoubtedly burden the mental health and quality of life of cancer patients; therefore, it is very important to reduce the adverse reactions of their medication

Method used

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  • Use of an anti-PD-1 antibody combined with a vegfr inhibitor in the preparation of a drug for treating cancer
  • Use of an anti-PD-1 antibody combined with a vegfr inhibitor in the preparation of a drug for treating cancer
  • Use of an anti-PD-1 antibody combined with a vegfr inhibitor in the preparation of a drug for treating cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: PD-1 antibody, apatinib mesylate alone or in combination with PD-L1 gene transferred mouse colon cancer cell MC-38 (PD-L1) transplanted tumor C57 human PD- 1 Efficacy of transgenic mice

[0044] 1. Research purpose

[0045] Human PD-1 transgenic mice were used as experimental animals to evaluate the effect of PD-1 antibody combined with apatinib on the transplanted tumor C57 of mouse colon cancer cell MC-38 (PD-L1) with PD-L1 gene Efficacy of Human PD-1 Transgenic Mice.

[0046] 2. Antibodies and compounds to be tested

[0047] The PD-1 antibody is prepared according to the method disclosed in WO2015085847, corresponding to its code name H005-1, and the sequences of its heavy and light chains are as SEQ ID NO: 7 and SEQ ID NO: 8 in the present invention. Batch number: P1512, 200mg / bottle, prepared as 20mg / ml for later use.

[0048] Apatinib mesylate, prepared according to the method disclosed in CN101676267A, batch number: 668160401; molecular weight: 493...

Embodiment 2

[0071] Example 2: Clinical study of anti-PD-1 antibody combined with apatinib mesylate in the treatment of advanced malignant tumors

[0072] Inclusion criteria: (1) Advanced malignant tumors; (2) Failure of first-line or second-line chemotherapy; (3) Measurable lesions; (4) ECOG score 0-1.

[0073] Test drug: commercially available apatinib mesylate tablets; PD-1 antibody in Example 1.

[0074] Administration method: As of September 20, 2017, a total of 31 subjects have been screened, and 30 subjects have been enrolled (14 subjects have withdrawn from treatment, and 16 subjects are still regrouped for administration) middle).

[0075]The administration method of 001-005 cases was intravenous infusion of PD-1 antibody, 3 mg / kg, every 2 weeks; oral administration of apatinib, 500 mg, once a day; the administration method of 006-010 cases was intravenous infusion of PD-1 antibody Infusion, 200mg, 2 weeks / time; Oral apatinib, 125mg, once a day; 011-031 cases, PD-1 antibody intr...

Embodiment 3

[0077] Example 3: Phase II clinical study of anti-PD-1 antibody combined with apatinib mesylate in the treatment of advanced non-small cell lung cancer

[0078] Inclusion criteria: (1) Advanced non-small cell lung cancer; (2) Failure of first-line or second-line chemotherapy; (3) Measurable lesions; (4) ECOG score 0-1.

[0079] Test drug: commercially available apatinib mesylate tablets; PD-1 antibody in Example 1.

[0080] Administration method: PD-1 antibody, once every 2 weeks, intravenous infusion, 200 mg each time; apatinib mesylate was taken orally once a day, 250 mg or 375 mg or 500 mg each time.

[0081] Clinical results: As of July 28, a total of 15 subjects have been screened, of which 12 have been enrolled. A total of 12 subjects completed at least one cycle of medication observation, 10 patients (10 / 12) had stable disease, and 1 patient had partial remission. See Table 5 for details. In addition, in the process of combining apatinib mesylate and PD-1 antibody, w...

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Abstract

The invention discloses the use of an anti-PD‑1 antibody combined with a VEGFR inhibitor in the preparation of a drug for treating cancer.

Description

technical field [0001] The invention relates to the use of an anti-PD-1 antibody combined with a VEGFR inhibitor in the preparation of a drug for treating cancer. Background technique [0002] The PD-1 antibody specifically recognizes and binds to PD-1 on the surface of lymphocytes, blocks the PD-1 / PD-L1 signaling pathway, and then activates the immune killing effect of T cells on tumors, and mobilizes the body's immune system to eliminate tumor cells in the body. WO201508584 discloses a new anti-PD-1 antibody, which is currently in clinical trials and has shown certain anti-tumor effects. [0003] Apatinib is the world's first oral anti-angiogenic drug for advanced gastric cancer. It is highly selective to VEGFR-2 and has a strong anti-angiogenic effect. In a multicenter randomized double-blind placebo-controlled phase III trial of apatinib in the second-line treatment of patients with metastatic gastric / gastroesophageal junction cancer, the results showed that compared wi...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K39/395C07K16/28A61P35/00
CPCA61P35/00C07K16/2818A61K2039/505A61K39/39558A61K31/444A61K2039/545A61K2039/86A61K2300/00A61K39/3955A61K45/06C07K16/28A61K39/395A61K9/0053A61K2039/54C07K2317/24C07K2317/565
Inventor 孙星曹国庆杨昌永张连山郭勇
Owner SUZHOU SUNCADIA BIOPHARM CO LTD
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