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

Study Overview
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Brief Summary
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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

Official Title
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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

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

Intervention / Treatment
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* Drug: SHR-1210
* Drug: Apatinib
* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with histopathological diagnosis of adenocarcinoma non-small cell lung cancer (NSCLC) and clinical stage IV has not received prior systemic treatment for metastatic NSCLC. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status confirmes by the central laboratory as KRAS gene mutation Has archived Tumor tissue samples Subject must have a measurable target lesion based on RECIST v1.1 . 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. Subjects should be voluntarily participate in clinical studies and informed consent should be signed. Exclusion Criteria: active brain metastases and meningeal metastasis uncontrollable tumor-related pain massive pleural effusion, peritoneal effusion or pericardial effusion which cannot be controlled by repeated drainage; radiotherapy to lung that is >30 Gy within 24 weeks before the first dose, imaging (CT or MRI) showed that the tumor invading the large vessels Known EGFR/ALK mutation. subjects with any known or suspected autoimmune diseases subjects with known or suspected interstitial pneumonia; Subjects with severe cardiovascular and cerebrovascular diseases arteriovenous thrombosis events, such as deep vein thrombosis and pulmonary embolism, occurred within 3 months; female subjects who are pregnant or lactation or who plan to be pregnant during the study period; positive HIV test; active hepatitis B evidence of active TB infection within 1 year before first dose; severe infection occurred within 4 weeks before the first dose patients with clinically significant bleeding symptoms or with obvious bleeding tendency in the first month subjects who is on systemic immunogenic agents; a history of severe allergic reactions to other monoclonal antibodies/fusion proteins; History of severe allergic reactions to carboplatin or pemetrexed or their preventive drugs;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1210 +apatinib<br>subject will receive SHR-1210 200mg every 2 weeks, apatinib 250mg every day | Drug: SHR-1210<br>* Subjects receive SHR-1210 intravenous every 2 weeks<br>Drug: Apatinib<br>* Subjects receive Apatinib orally every day<br>|
| Active Comparator: chemotherapy<br>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 | Drug: Pemetrexed<br>* Subjects receive Pemetrexed intravenous every 3 weeks<br>Drug: Carboplatin<br>* subjects receive carboplatin intravenous every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Progression-Free Survival (PFS) as Assessed by the Independent Review Committee Using RECIST v1.1 | PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee Using RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment. | up to approximately 40 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 | Time Frame: Baseline until PD or death, whichever occurs first | up to approximately 40 months | 
| Duration of Overall Survival (OS) | Baseline until death from any cause | up to approximately 40 months | 
| Objective Response Rate (ORR) | The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1. | up to approximately 40 months | 
| disease control rate (DCR) | The proportion of patients who have achieved complete response， partial response and Stable disease assessed by investigators according to Recist v 1.1. | up to approximately 40 months | 
| Duration of response （DoR） | Duration of response （DoR） | up to approximately 40 months | 
| Adverse events (AEs) | All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 5.0 | up to approximately 40 months |