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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chemotherapy Effect; Lung Cancer Stage IV; PD-1 Antibody; Lung Cancer Squamous Cell
• Intervention / Treatment: Drug: SHR-1210; Drug: The placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230036
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230036
      • The Second Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China, MD
      • Anhui Chest Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100000
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100000
      • The Fifth Medical Center of PLA Ceneral Hospital
    • Beijing, Beijing, China, 100000
      • The Seventh Medical Center of PLA Ceneral Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing University Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • 900TH Hospital of Joint Logistics Support Force
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
    • Guangzhou, Guangdong, China, 510095
      • Affiliated Cancer Hospital and Institute of Guangzhou Medical University
    • Jieyang, Guangdong, China, 522000
      • Jieyang People's Hospital
  • Guizhou
    • Zunyi, Guizhou, China, 563003
      • Affiliated Hospital of Zunyi Medical University
  • Hebei
    • Chengde, Hebei, China, 067000
      • Affiliated Hospital of Chengde Medical College
    • Shijiazhuang, Hebei, China, 50000
      • The Fourth Hospital of Hebei Medical University (Hebei Cancer Hospital)
    • Tangshan, Hebei, China, 63001
      • Tangshan People's Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Provincial People's Hospital
    • Zhengzhou, Henan, China, 450000
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430000
      • Tongji Hospital, Tongji Medical College of HUST
    • Xiangyang, Hubei, China, 441000
      • Xiang yang Central Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410008
      • The Second Xiangya Hospital Of Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Drum Tower hospital
    • Nanjing, Jiangsu, China, 210000
      • Jiangsu Province Hospital
    • Wuxi, Jiangsu, China, 214122
      • Affiliated Hospital of Jiangnan University
    • Yangzhou, Jiangsu, China, 225001
      • Northern Jiangsu People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital Of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Cancer Hospital
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital
    • Changchun, Jilin, China, 130012
      • China-Japan Union Hospital of Jilin University
    • Changchun, Jilin, China, 130012
      • The First Bethune Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Linyi, Shandong, China, 276001
      • LinYi Cancer Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Changhai Hospital
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital, Tongji University
  • Shanxi
    • Baoji, Shanxi, China, 721000
      • Baoji Central Hospital
    • Changzhi, Shanxi, China, 046000
      • Heping Hospital Affiliated to Changzhi Medical College
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Provincial People's Hospital
    • Xian, Shanxi, China, 710061
      • Shaanxi Provincial Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Sichuan Provincial Cancer Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
  • Zhejiang
    • HangZhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The first affiliated hospital,zhejiang university
    • Hangzhou, Zhejiang, China, 310018
      • Sir Run Run Shaw Hospital Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310052
      • The Second Affiliated Hospital of Zhejiang University of Medicine
    • Taizhou, Zhejiang, China, 317000
      • Taizhou Hospital of Zhejiang Province

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects with histopathological diagnosis of squamous non-small cell lung cancer (SqNSCLC) 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. Has archived Tumor tissue samples
5. Subject must have a measurable target lesion based on RECIST v1.1 .
6. Has adequate organ function.
7. 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.
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 paclitaxel or their preventive drugs;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-1210 +chemotherapy; 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; 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.
Active Comparator: chemotherapy; 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; in the control group,placebo was given with Carboplatin and Paclitaxel in the first day of each cycle, with intravenous drip.

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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Study Director: Jianjun Zou, MD, PhD, Jiangsu HengRui Medicine Co., Ltd.; Principal Investigator: Caicun Zhou, MD, PhD, Tongji University, Shanghai Pulmonary Hospital

Publications and helpful links

General Publications

• Jiang T, Chen J, Xu X, Cheng Y, Chen G, Pan Y, Fang Y, Wang Q, Huang Y, Yao W, Wang R, Li X, Zhang W, Zhang Y, Hu S, Guo R, Shi J, Wang Z, Cao P, Wang D, Fang J, Luo H, Geng Y, Xing C, Lv D, Zhang Y, Yu J, Cang S, Zhang Y, Zhang J, Yang Z, Shi W, Zou J, Zhou C, Ren S. On-treatment blood TMB as predictors for camrelizumab plus chemotherapy in advanced lung squamous cell carcinoma: biomarker analysis of a phase III trial. Mol Cancer. 2022 Jan 3;21(1):4. doi: 10.1186/s12943-021-01479-4.
• Ren S, Chen J, Xu X, Jiang T, Cheng Y, Chen G, Pan Y, Fang Y, Wang Q, Huang Y, Yao W, Wang R, Li X, Zhang W, Zhang Y, Hu S, Guo R, Shi J, Wang Z, Cao P, Wang D, Fang J, Luo H, Geng Y, Xing C, Lv D, Zhang Y, Yu J, Cang S, Yang Z, Shi W, Zou J, Zhou C; CameL-sq Study Group. Camrelizumab Plus Carboplatin and Paclitaxel as First-Line Treatment for Advanced Squamous NSCLC (CameL-Sq): A Phase 3 Trial. J Thorac Oncol. 2022 Apr;17(4):544-557. doi: 10.1016/j.jtho.2021.11.018. Epub 2021 Dec 16.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2018
• Primary Completion (Actual): November 6, 2020
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: September 11, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 15, 2021
• Last Update Submitted That Met QC Criteria: March 12, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: SHR-1210-III-307

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No