Study of Platinum Plus Etoposide With or Without BGB-A317 in Participants With Untreated Extensive-Stage Small Cell Lung Cancer

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

This is a randomized, double-blind, placebo-controlled, multicenter, Phase 3 study to compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide (Arm A) and placebo + cisplatin or carboplatin + etoposide (Arm B) as first-line treatment in approximately 455 participants who have previously untreated extensive-stage small cell lung cancer (ES-SCLC)

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Tislelizumab, Carboplatin /Cisplatin, Etoposide; Drug: Carboplatin / Cisplatin, Etoposide

• Study Type: Interventional
• Enrollment (Actual): 457
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100029
      • China-Japan Friendship Hospital
    • Beijing, Beijing, China, 100039
      • Chinese PLA General Hospital
    • Beijing, Beijing, China, 100005
      • Beijing Hospital
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100191
      • The Third Hospital of Peking University
    • Beijing, Beijing, China, 102206
      • Name:Peking University International Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Army Special Medical Center (Daping Hospital)
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Fuzhou, Fujian, China, 361003
      • Fujian Medical University Union Hospital
    • Xiamen, Fujian, China, 361003
      • First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
    • Guangzhou, Guangdong, China, 510059
      • Cancer Center of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510059
      • The First Affiliated Hospital of Guangzhou Medical University
  • Guangxi
    • Guilin, Guangxi, China, 541001
      • Affiliated Hospital of Guilin Medical University
    • Nanning, Guangxi, China, 530021
      • Affiliated Tumor Hospital of Guangxi Medical University
    • Nanning, Guangxi, China, 168600
      • Guangxi Zhuang Autonomous Region People's Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Affiliated Tumor Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China, 450052
      • First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Tongji Hospital Tongji Medical College Huazhong University of Sciences and Technology
    • Wuhan, Hubei, China, 430000
      • Union Hospital Tongji Medical College Huazhong University of Sciences and Technology
    • Wuhan, Hubei, China, 430014
      • The Central Hospital Wuhan
  • Hunan
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University
    • Changsha, Hunan, China, 410018
      • Changsha Central Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • General Hospital of Nanjing Military Command
    • Nanjing, Jiangsu, China, 210029
      • Nanjing Chest Hospital
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital
    • Shenyang, Liaoning, China, 110001
      • The first affiliated hospital of China medical university
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Qingdao, Shandong, China, 266003
      • Affiliated Hospital of Qingdao University
    • Yantai, Shandong, China, 264000
      • Yantai Yuhuangding Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Shanghai Pulmonary Hospital
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital
  • Shannxi
    • Xi'an, Shannxi, China, 710061
      • Shannxi Provincial Cancer Hospital
    • Xi'an, Shannxi, China, 710061
      • The First Affiliated Hospital of Xi 'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610042
      • Sichuan Cancer Hospital
    • Chengdu, Sichuan, China, 610041
      • West China Hospital · Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Cancer Hospital
    • Tianjin, Tianjin, China, 300070
      • General Hospital of Tianjin Medical University
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830000
      • Affiliated Tumor Hospital of Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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: tislelizumab plus etoposide and platinum	Drug: Tislelizumab, Carboplatin /Cisplatin, Etoposide; Tislelizumab (200 mg IV Q3W) in combination with chemotherapy consisting of etoposide (100 mg/m² IV Days 1-3 of each 21-day cycle) and platinum (cisplatin 75 mg/m² IV Q3W or carboplatin area under the plasma or serum concentration-time curve (AUC) 5 IV Q3W) for 4 cycles. Then maintenance consists of Tislelizumab Q3W and will continue until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of informed consent.
Active Comparator: Placebo plus etoposide and platinum	Drug: Carboplatin / Cisplatin, Etoposide; Placebo Q3W in combination with chemotherapy consisting of etoposide (100 mg/m² IV Days 1-3 of each 21-day cycle) and platinum (cisplatin 75 mg/m² IV Q3W or carboplatin AUC 5 IV Q3W) for 4 cycles. Then maintenance consists of Placebo Q3W and will continue until disease progression, loss of clinical benefit, unacceptable toxicity, or withdrawal of informed consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the intent to treat Analysis Set as measured by overall survival (OS)	Baseline until death from any cause (up to approximately 51 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the ITT Analysis Set as measured by investigator assessed overall response rate (ORR), according to RECIST v1.1	Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 29 months)
Duration Of Response (DOR)	To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the ITT Analysis Set as measured by investigator assessed duration of response (DOR) according to RECIST v1.1	Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 29 months)
Disease Control Rate (DCR)	To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the ITT Analysis Set as measured by investigator assessed disease control rate (DCR) according to RECIST v1.1	up to approximately 29 months
Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events		up to approximately 51 months
Percentage of patients with clinically meaningful changes post baseline		up to approximately 29
Time to deterioration (TTD), defined as the time from randomization to the first occurrence of worsening scores confirmed at the following visit or death from any cause		up to approximately 29 months
Progression Free Survival (PFS)	To evaluate and compare the efficacy of tislelizumab + cisplatin or carboplatin + etoposide compared with placebo + cisplatin or carboplatin + etoposide in the intent to treat (ITT) Analysis Set as measured by investigator assessed progression free survival (PFS) according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Baseline until PD or death, whichever occurs first (up to approximately 29 months)

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Ying Cheng, Professor, Jilin Provincial Tumor Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2019
• Primary Completion (Actual): April 19, 2023
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: July 1, 2019
• First Submitted That Met QC Criteria: July 1, 2019
• First Posted (Actual): July 2, 2019

Study Record Updates

• Last Update Posted (Actual): May 26, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

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; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Etoposide phosphate; Cisplatin; Tislelizumab
• Other Study ID Numbers: BGB-A317-312; CTR20190511 (Registry Identifier: Center for drug evaluation, NMPA)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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