Clinical trial NCT04005716: Study of Platinum Plus Etoposide With or Without Tislelizumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Etoposide With or Without Tislelizumab (BGB-A317) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Small Cell Lung Cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2019-07-02
Enrollment: 457
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This Phase 3 study was a randomized, double-blind, placebo-controlled, multicenter trial designed to evaluate the efficacy of tislelizumab in combination with either cisplatin or carboplatin and etoposide (Arm A), compared to placebo combined with either cisplatin or carboplatin and etoposide (Arm B), as a first-line treatment for participants with previously untreated extensive-stage small cell lung cancer (ES-SCLC).


Eligibility criteria: Key Inclusion Criteria:

1. Age≥18 years old, male or female, signed Informed Consent Form (ICF).
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
3. Histologically or cytologically confirmed ES-SCLC
4. No prior systemic treatment for ES-SCLC
5. Adequate hematologic and end organ function

Key Exclusion Criteria:

1. Active leptomeningeal disease or uncontrolled, untreated brain metastasis;
2. Prior therapy with an antibody or drug against immune checkpoint pathways, including but not limited to, anti program death receptor-1 (anti-PD-1), anti-PD-L1, or anti cytotoxic T lymphocyte associated antigen 4 (anti CTLA-4) antibody;
3. Was administered a live vaccine ≤ 4 weeks before randomization;
4. Active autoimmune diseases or history of autoimmune diseases that may relapse
5. Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication ≤ 14 days before randomization;
6. With a history of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases;
7. Severe chronic or active infections requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks prior to randomization, including but not limited to tuberculosis infection;
8. Participant with untreated hepatitis B virus (HBV)/hepatitis C virus (HCV), or a known history of HIV infection;
9. Participants with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or stabilized at the time of randomization;
10. Clinically significant pericardial effusion, or Clinically uncontrolled pleural effusion

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization to the primary completion cut-off on April 19, 2023, the median follow-up was 15.44 months (range: 0.2-44.9) for Arm A and 13.22 months (range: 0.1-40.8) for Arm B.
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomization to the primary completion cut-off on April 19, 2023, the median follow-up was 15.44 months (range: 0.2-44.9) for Arm A and 13.22 months (range: 0.1-40.8) for Arm B.
measure: Overall Response Rate (ORR)
timeFrame: From randomization to the primary completion cut-off on April 19, 2023, the median follow-up was 15.44 months (range: 0.2-44.9) for Arm A and 13.22 months (range: 0.1-40.8) for Arm B.
measure: Disease Control Rate (DCR)
timeFrame: From randomization to the primary completion cut-off on April 19, 2023, the median follow-up was 15.44 months (range: 0.2-44.9) for Arm A and 13.22 months (range: 0.1-40.8) for Arm B.
measure: Clinical Benefit Rate (CBR)
timeFrame: From randomization to the primary completion cut-off on April 19, 2023, the median follow-up was 15.44 months (range: 0.2-44.9) for Arm A and 13.22 months (range: 0.1-40.8) for Arm B.
measure: Duration of Response (DOR)
timeFrame: From randomization to the primary completion cut-off on April 19, 2023, the median follow-up was 15.44 months (range: 0.2-44.9) for Arm A and 13.22 months (range: 0.1-40.8) for Arm B.
measure: Number of Participants With Adverse Events
timeFrame: From the first dose to 30 days after the last dose or final cutoff on December 29, 2023, maximum treatment exposure was 232 weeks for Arm A and 157 weeks for Arm B.
measure: Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status and Physical Function Score.
timeFrame: Baseline to Cycles 4 and 6 ( Each cycle was 21 days)
measure: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) Symptom Scores
timeFrame: Baseline to Cycles 4 and 6 ( Each cycle was 21 days)
measure: Time to Deterioration (TTD)
timeFrame: From randomization to the primary completion data cut-off on April 19, 2023, the median follow-up was 15.44 months (range: 0.2-44.9) for Arm A and 13.22 months (range: 0.1-40.8) for Arm B.
Other outcomes:
Locations:
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Beijing
country: China
facility: China Japan Friendship Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese Pla General Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University International Hospital
state: Beijing
city: Chongqing
country: China
facility: Daping Hospital, Third Military Medical University
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Nanning
country: China
facility: The Peoples Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Nanning
country: China
facility: The Tumor Hospital Affiliated to Guangxi Medical University
state: Guangxi
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: Wuhan
country: China
facility: Wuhan Central Hospital
state: Hubei
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Changsha Central Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: General Hospital of Eastern Theater Command
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Chest Hospital
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Xian
country: China
facility: Shaanxi Provincial Cancer Hospital
state: Shaanxi
city: Xian
country: China
facility: The First Affiliated Hospital of Xian Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University Branch South
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai Chest Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Chengdu
country: China
facility: Sichuan Cancer Hospital and Institute
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
city: Urumqi
country: China
facility: Affiliated Cancer Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Study Director
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Cheng Y, Fan Y, Zhao Y, Huang D, Li X, Zhang P, Kang M, Yang N, Zhong D, Wang Z, Yu Y, Zhang Y, Zhao J, Qin T, Chen C, Leaw S, Zheng W, Song Y; RATIONALE-312 Study Group. Tislelizumab Plus Platinum and Etoposide Versus Placebo Plus Platinum and Etoposide as First-Line Treatment for Extensive-Stage SCLC (RATIONALE-312): A Multicenter, Double-Blind, Placebo-Controlled, Randomized, Phase 3 Clinical Trial. J Thorac Oncol. 2024 Jul;19(7):1073-1085. doi: 10.1016/j.jtho.2024.03.008. Epub 2024 Mar 7.
citation: Wu J, Zhang A, Li L, Liu S, Yang F, Yang R. Meta-analysis of the Efficacy and Tolerability of Immune Checkpoint Inhibitors Combined With Chemotherapy in First-line Treatment of Small Cell Lung Cancer. Clin Ther. 2021 Mar;43(3):582-593.e2. doi: 10.1016/j.clinthera.2020.12.017. Epub 2021 Jan 25.