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Method for treating lung cancer by combining anti-PD-L1 antibody with radioactive rays

A technology of PD-L1 and radiation therapy, applied in the field of biomedicine, can solve problems such as low survival rate, poor treatment effect of patients, and poor effect of immunotherapy

Pending Publication Date: 2021-08-31
CHIA TAI TIANQING PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Immune checkpoint inhibitors targeting the PD-1 / PD-L1 pathway have significantly improved the prognosis of patients with non-small cell lung cancer, but most patients have poor treatment effects due to primary drug resistance
In a study using the PD-1 / PD-L1 pathway inhibitor Nivolumab (Gettinger S et al. (2018) ClinOncol.36(17):1675-1684), low expression of PD-L1 and no Patients with PD-L1 expression accounted for 80.1% (55 / 68), and the survival rate of these patients was also significantly lower than that of patients with high PD-L1 expression. According to the analysis, there may be primary drug resistance in patients, resulting in poor immunotherapy effect

Method used

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  • Method for treating lung cancer by combining anti-PD-L1 antibody with radioactive rays
  • Method for treating lung cancer by combining anti-PD-L1 antibody with radioactive rays

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0083] Embodiment 1 preclinical pharmacodynamics test

[0084] This example discloses the experimental results of pharmacodynamic studies of anti-PD-L1 antibodies in vitro and in mice.

[0085] hu5G11-hIgG1 binds to human PD-L1 protein, and its EC50 is 21.3 ng / mL; hu5G11-hIgG1 and human PD-L1 significantly induce the secretion of IFN-γ in the MLR of CD4+:DC cells, and the effect is dose-dependent. The EC50 was 35.0±11.3ng / mL, indicating that hu5G11-hIgG1 combined with PD-L1 expressed by DCs inhibited the PD-L1 / PD-1 signaling pathway, thereby stimulating the secretion of IFN-γ in CD4+ T cells.

[0086] The tumor inhibition rate of hu5G11-hIgG1 (15mg / kg, IP, Q2D×11) on MC-38 / H-11 mice subcutaneously transplanted tumor was 91.7% (calculated according to the median tumor volume), and significantly prolonged the intraperitoneal inoculation. The survival time of mice with mouse MC-38 / H-11 cells, the median survival time was >98 days, and the survival rate at the end of the experime...

Embodiment 2

[0088] Embodiment 2. preclinical toxicology test

[0089] This example discloses the results of acute toxicity tests and long-term toxicity tests of anti-PD-L1 antibodies in animals.

[0090] Six cynomolgus monkeys were used and divided into 2 groups with 3 monkeys in each group, both male and female. The pharmaceutical composition of the present invention containing hu5G11-hIgG1 was administered at a concentration of 10 mg / mL according to the doses of hu5G11-hIgG1 200 and 400 mg / kg, respectively. The day of administration was regarded as the first day of the experiment. Observe the general condition of cynomolgus monkeys in each group for 14 consecutive days after administration; measure body weight before administration and on the 4th, 9th, and 14th day of the test; Measure body temperature, II-lead electrocardiogram, and blood pressure before administration, about 0 to 1 hour after administration, and on the 14th day of the test; hematology and blood biochemical tests wer...

Embodiment 3

[0092] Example 3. Phase I clinical trial protocol and safety and tolerability results

[0093] This example discloses the preliminary efficacy results of pharmacokinetics and tolerability of a single-center, open-type, dose-escalation clinical phase I trial.

[0094] The phase I clinical tolerance and pharmacokinetic study included patients with advanced malignant tumors who had a definite diagnosis and failed standard treatment or lacked standard treatment, observed the safety and tolerability of the pharmaceutical composition containing hu5G11-hIgG1, and determined the maximum tolerance Dose-limited toxicity (MTD) and dose-limiting toxicity (DLT).

[0095] Primary endpoints: DLT; MTD.

[0096] Secondary endpoints: Pharmacokinetic evaluation; Preliminary study on the effect of anti-tumor therapy.

[0097] The safety and tolerability results showed that 1, 3, 10, 20, and 30 mg / kg of the pharmaceutical composition containing hu5G11-hIgG1 were administered to the enrolled pati...

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Abstract

The invention provides a method for treating lung cancer by combining an anti-PD-L1 antibody with radioactive rays. The method comprises the step of applying the anti-PD-L1 monoclonal antibody to a lung cancer patient who has previously been subjected to radiotherapy. According to the method, radiotherapy can reduce the primary or secondary resistance to the anti-PD-L1 antibody and further enhance the curative effect of the anti-PD-L1 antibody.

Description

technical field [0001] The invention belongs to the field of biomedicine, and provides an anti-PD-L1 antibody used in the preparation of a drug for treating, alleviating or improving lung cancer in a subject, wherein the subject has previously received radiation therapy. Background technique [0002] Radiation therapy for tumors is a local treatment method that uses radiation to treat tumors. Radiation includes α, β, γ rays produced by radioactive isotopes and x-rays, electron beams, proton beams and other particle beams produced by various x-ray therapy machines or accelerators. The role and status of radiotherapy in tumor treatment has become increasingly prominent, and it has become one of the main means of treating malignant tumors. Stereotactic Body Radiation Therapy (SBRT) is a hypofractionated, less-fractionated, and short-course radiation therapy mode. Generally, 3-5 high-dose radiation treatments are given to tumor lesions. [0003] Stereotactic radiotherapy has b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K41/00A61P11/00A61P35/00
CPCA61K39/3955A61K41/0038A61K2039/505A61P11/00A61P35/00C07K16/2827A61K2300/00
Inventor 梁洪铭张喜全王训强于鼎王栋葛琪
Owner CHIA TAI TIANQING PHARMA GRP CO LTD