A Study of SHR-1210 in Combination With Carboplatin + Paclitaxel in Subjects With Squamous NSCLC

Study Overview
=================
Brief Summary
-----------------
This study is a randomized, placebo-controlled, double-blind, multicenter phase III clinical study. Target population is patients with stage IV squamous non-small cell lung cancer who had not received systemic chemotherapy. Study objective is to compare the efficacy and safety of SHR-1210 + carboplatin + paclitaxel with placebo + carboplatin + paclitaxel in study population in China. SHR-1210 is a humanized anti-PD1 IgG4 monoclonal antibody.

Detailed Description
-----------------
In this study, eligible subject will be randomized into study arm or control arm to accept study treatment. Subjects who randomized into control will have the opportunity to receive cross over treatment of SHR-1210 monotherapy after confirmed disease progression. Treatment cycles of chemotherapy will be 4-6 which will be decided by investigators.

Official Title
-----------------
A Phase III, Randomized,Double-Blind, Multi-center Study to Investigate the Efficacy and Safety of SHR-1210 in Combination With Carboplatin and Paclitaxel Versus Placebo in Combination With Carboplatin and Paclitaxel in First-Line Stage IV Squamous Non-Small Cell Lung Cancer

Conditions
-----------------
Lung Cancer Squamous Cell, Lung Cancer Stage IV, PD-1 Antibody, Chemotherapy Effect

Intervention / Treatment
-----------------
* Drug: SHR-1210
* Drug: The placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with histopathological diagnosis of squamous non-small cell lung cancer (SqNSCLC) 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 Has archived Tumor tissue samples Subject must have a measurable target lesion based on RECIST v1.1 . Has adequate organ function. Women of childbearing age must undergo a serological pregnancy test within 7 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 paclitaxel or their preventive drugs;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1210 +chemotherapy<br>subject will receive SHR-1210 200mg every 3 weeks, carboplatin AUC 5 on Day 1 of each 21 day, 4-6 cycles Paclitaxel 175mg/m2, Day 1 of each 21 day, 4-6 cycles | Drug: SHR-1210<br>* Drug delivery cycle is 3 weeks, and in the experimental group,200 mg shr-1210 was given with Carboplatin and Paclitaxel in the first day of each cycle, with intravenous drip.<br>|
| Active Comparator: chemotherapy<br>carboplatin AUC 5 on Day 1 of each 21 day, 4-6 cycles Paclitaxel 175mg/m2, Day 1 of each 21 day, 4-6 cycles | Drug: The placebo<br>* in the control group,placebo was given with Carboplatin and Paclitaxel in the first day of each cycle, with intravenous drip.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee according to RECIST v1.1 or death from any cause, whichever occurs first. | up to 24 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival (PFS) assessed by investigators according to RECIST V 1.1 | up to 24 month | 
| Overall Survival (OS) | defined as time from the randomized to the time of the patient's death from any reason assessed by researchers. | up to 24 month | 
| Objective Response Rate (ORR) | The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1. | up to 24 month | 
| 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 24 month | 
| Duration of response （DoR） | According to Recist v 1.1 accessed by investigators | up to 24 month | 
| Adverse events (AEs) | All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 4.03 | up to 24 month |