Clinical trial NCT03668496: A Study of SHR-1210 in Combination With Carboplatin + Paclitaxel in Subjects With Squamous NSCLC
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lung Cancer Squamous Cell
Lung Cancer Stage IV
PD-1 Antibody
Chemotherapy Effect
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-09-12
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: up to 24 month
Secondary outcomes:
measure: Progression-free survival
timeFrame: up to 24 month
measure: Overall Survival (OS)
timeFrame: up to 24 month
measure: Objective Response Rate (ORR)
timeFrame: up to 24 month
measure: disease control rate (DCR)
timeFrame: up to 24 month
measure: Duration of response （DoR）
timeFrame: up to 24 month
measure: Adverse events (AEs)
timeFrame: up to 24 month
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital Of Anhui Medical University
state: Anhui
city: Hefei
country: China
facility: Anhui Chest Hospital
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: The Fifth Medical Center of PLA Ceneral Hospital
state: Beijing
city: Beijing
country: China
facility: The Seventh Medical Center of PLA Ceneral Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: 900TH Hospital of Joint Logistics Support Force
state: Fujian
city: Guangzhou
country: China
facility: Affiliated Cancer Hospital and Institute of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Jieyang
country: China
facility: Jieyang People's Hospital
state: Guangdong
city: Zunyi
country: China
facility: Affiliated Hospital of Zunyi Medical University
state: Guizhou
city: Chengde
country: China
facility: Affiliated Hospital of Chengde Medical College
state: Hebei
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University (Hebei Cancer Hospital)
state: Hebei
city: Tangshan
country: China
facility: Tangshan People's Hospital
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of Hust
state: Hubei
city: Xiangyang
country: China
facility: Xiang yang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: The Second Xiangya Hospital Of Central South University
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital Of Central South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Yangzhou
country: China
facility: Northern Jiangsu People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: China-Japan Union Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Linyi
country: China
facility: LinYi Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Changhai Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital, Tongji University
state: Shanghai
city: Baoji
country: China
facility: Baoji Central Hospital
state: Shanxi
city: Changzhi
country: China
facility: Heping Hospital Affiliated to Changzhi Medical College
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Xian
country: China
facility: Shaanxi Provincial Cancer Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial Cancer Hospital
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital & The Third Affiliated Hospital of Kunming Medical University & Yunnan Cancer Center
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital，ZheJiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital ZheJiang University School Of Medicine
state: Zhejiang
city: HangZhou
country: China
facility: ZheJiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University of Medicine
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
Study officials:
affiliation: Jiangsu HengRui Medicine Co., Ltd.
name: Jianjun Zou, MD, PhD
role: STUDY_DIRECTOR
affiliation: Tongji University, Shanghai Pulmonary Hospital
name: Caicun Zhou, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.