Phase II Study of SHR-1210(Anti-PD-1 Antibody) Combination With Apatinib Versus Pemetrexed and Carboplatin in Subjects With KRAS Mutant Stage IV Non-squamous Non-small Cell Lung Cancer

Hengrui Medicine

Status and phase: Unknown; Phase 2

Conditions: Chemotherapy Effect; NSCLC Stage IV; PD-1 Antibody; KRAS Gene Mutation

Treatments: Drug: Pemetrexed; Drug: SHR-1210; Drug: Carboplatin; Drug: Apatinib

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03777124

SHR-1210-II-214

Details and patient eligibility

About

This is a randomized, open-label, multi-center, phase II trial to evaluate the efficacy and safety of SHR-1210 plus apatinib mesylate versus Pemetrexed and Carboplatin in Subjects with KRAS mutant stage IV non-squamous Non-small Cell Lung Cancer

Enrollment: 230 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subjects with histopathological diagnosis of adenocarcinoma non-small cell lung cancer (NSCLC) and clinical stage IV
2. has not received prior systemic treatment for metastatic NSCLC.
3. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
4. confirmes by the central laboratory as KRAS gene mutation
5. Has archived Tumor tissue samples
6. Subject must have a measurable target lesion based on RECIST v1.1 .
7. Women of childbearing age must undergo a serological pregnancy test within 3 days before the first dose with negative results. Female subjects of reproductive age and male subjects whose spouse is a woman of reproductive age must agree to effective contraception within 180 days after the study period and the last dose of the study drug.
8. Subjects should be voluntarily participate in clinical studies and informed consent should be signed.

Exclusion criteria

1. active brain metastases and meningeal metastasis
2. uncontrollable tumor-related pain
3. massive pleural effusion, peritoneal effusion or pericardial effusion which cannot be controlled by repeated drainage;
4. radiotherapy to lung that is >30 Gy within 24 weeks before the first dose,
5. imaging (CT or MRI) showed that the tumor invading the large vessels
6. Known EGFR/ALK mutation.
7. subjects with any known or suspected autoimmune diseases
8. subjects with known or suspected interstitial pneumonia;
9. Subjects with severe cardiovascular and cerebrovascular diseases
10. arteriovenous thrombosis events, such as deep vein thrombosis and pulmonary embolism, occurred within 3 months;
11. female subjects who are pregnant or lactation or who plan to be pregnant during the study period;
12. positive HIV test;
13. active hepatitis B
14. evidence of active TB infection within 1 year before first dose;
15. severe infection occurred within 4 weeks before the first dose
16. patients with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month
17. subjects who is on systemic immunogenic agents;
18. a history of severe allergic reactions to other monoclonal antibodies/fusion proteins;
19. History of severe allergic reactions to carboplatin or pemetrexed or their preventive drugs;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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230 participants in 2 patient groups

SHR-1210 +apatinib

Experimental group

Description:

subject will receive SHR-1210 200mg every 2 weeks, apatinib 250mg every day

Treatment:

Drug: SHR-1210

Drug: Apatinib

chemotherapy

Active Comparator group

Description:

Pemetrexed 500mg/m2, Day 1 of each 21 day, 4 cycles carboplatin AUC 5 on Day 1 of each 21 day, 4 cycles followed by pemetrexed 500mg/m2 until progression Q3W

Treatment:

Drug: Carboplatin

Drug: Pemetrexed