Study of Platinum Plus Etoposide With or Without Tislelizumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer
- Conditions
- Small Cell Lung Cancer
- Interventions
- Drug: Tislelizumab, Carboplatin /Cisplatin, EtoposideDrug: Placebo
- Registration Number
- NCT04005716
- Lead Sponsor
- BeiGene
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 457
- Age≥18 years old, male or female, signed Informed Consent Form (ICF).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically or cytologically confirmed ES-SCLC
- No prior systemic treatment for ES-SCLC
- Adequate hematologic and end organ function
Key
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis;
- 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;
- Was administered a live vaccine ≤ 4 weeks before randomization;
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Any condition that required systemic treatment with either corticosteroids or other immunosuppressive medication ≤ 14 days before randomization;
- With a history of interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases;
- 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;
- Participant with untreated hepatitis B virus (HBV)/hepatitis C virus (HCV), or a known history of HIV infection;
- Participants with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or stabilized at the time of randomization;
- Clinically significant pericardial effusion, or Clinically uncontrolled pleural effusion
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Tislelizumab + Chemotherapy Tislelizumab Participants received tislelizumab in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, administered every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with tislelizumab only, administered once every 3 weeks. Arm A: Tislelizumab + Chemotherapy Cisplatin Participants received tislelizumab in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, administered every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with tislelizumab only, administered once every 3 weeks. Arm A: Tislelizumab + Chemotherapy Carboplatin Participants received tislelizumab in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, administered every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with tislelizumab only, administered once every 3 weeks. Arm A: Tislelizumab + Chemotherapy Etoposide Participants received tislelizumab in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, administered every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with tislelizumab only, administered once every 3 weeks. Arm B: Placebo + Chemotherapy Cisplatin Participants received a placebo in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, given every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with placebo only, administered once every 3 weeks. Arm B: Placebo + Chemotherapy Carboplatin Participants received a placebo in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, given every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with placebo only, administered once every 3 weeks. Arm B: Placebo + Chemotherapy Etoposide Participants received a placebo in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, given every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with placebo only, administered once every 3 weeks. Arm B: Placebo + Chemotherapy Placebo Participants received a placebo in combination with either cisplatin or carboplatin (at the investigator's discretion) and etoposide during the induction phase, given every 3 weeks for 4 cycles. Upon completion of the induction phase, participants transitioned to maintenance therapy with placebo only, administered once every 3 weeks. tislelizumab plus etoposide and platinum Tislelizumab, Carboplatin /Cisplatin, Etoposide - Placebo plus etoposide and platinum Carboplatin / Cisplatin, Etoposide -
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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. Defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using Kaplan-Meier methodology.
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) 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. Defined as the time from randomization to the first objectively documented disease progression, or death from any cause, whichever occurred first, as assessed by the investigator per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Kaplan-Meier methodology was used to estimate the median PFS.
Progressive Disease (PD): At least a 20% increase in the size of target lesions, with an absolute increase of at least 5 mm, or unequivocal progression of existing non-target lesions, or any new lesions.Overall Response Rate (ORR) 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. Orr is defined as the percentage of participants who had partial response or complete response as determined by the investigator per RECIST v1.1 in all randomized patients with measurable disease at baseline.
Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions with no progression of non-target lesions and no new lesions, or disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits and no new lesions.Disease Control Rate (DCR) 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. Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or stable disease per RECIST v1.1.
Stable Disease: Neither sufficient shrinkage of target lesions to qualify for PR nor sufficient increase to qualify for progressive disease, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions.Clinical Benefit Rate (CBR) 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. Defined as the percentage of participants whose best overall response (BOR) is complete response, partial response, or durable stable disease (stable disease for at least 24 weeks) per RECIST v1.1.
Duration of Response (DOR) 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. Defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by the investigator per RECIST v1.1, or death from any cause, whichever comes first. Median DOR was estimated using Kaplan-Meier methodology.
Number of Participants With Adverse Events 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. Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
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. Baseline to Cycles 4 and 6 ( Each cycle was 21 days) The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life.
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) Symptom Scores Baseline to Cycles 4 and 6 ( Each cycle was 21 days) Change from baseline in EORTC QLQ-CL13 scores for coughing, dysphagia, and chest pain. The EORTC QLQ-LC13 is a questionnaire that measures lung cancer-specific disease and treatment symptoms. It includes questions about specific symptoms in which participants respond based on a 4-point scale, where 1 is "not at all" and 4 is "very much". Raw scores are transformed into a 0 to 100 scale via linear transformation. A lower score indicates an improvement in symptoms.
Time to Deterioration (TTD) 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. Time to deterioration is defined as the time from randomization to the first confirmed worsening score or death. Clinically meaningful deterioration is defined as a ≥10-point decrease from baseline in QLQ-C30 physical functioning and a ≥10-point increase in QLQ-LC13 coughing and chest pain scores. If a participant did not have an event (death or deterioration), they were censored at their last clinic visit at which corresponding score was measured. Median TTD was estimated using Kaplan-Meier methodology.
Trial Locations
- Locations (50)
The Tumor Hospital Affiliated to Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Wuhan Central Hospital
🇨🇳Wuhan, Hubei, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
General Hospital of Eastern Theater Command
🇨🇳Nanjing, Jiangsu, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Liaoning, China
Shaanxi Provincial Cancer Hospital
🇨🇳Xian, Shaanxi, China
The First Affiliated Hospital of Xian Jiaotong University
🇨🇳Xian, Shaanxi, China
The Affiliated Hospital of Qingdao University Branch South
🇨🇳Qingdao, Shandong, China
Sichuan Cancer Hospital and Institute
🇨🇳Chengdu, Sichuan, China
West China Hospital, Sichuan University
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Affiliated Cancer Hospital of Xinjiang Medical University
🇨🇳Urumqi, Xinjiang, China
The Peoples Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, Guangxi, China
Peking University Third Hospital
🇨🇳Beijing, Beijing, China
China Japan Friendship Hospital
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Chinese Pla General Hospital
🇨🇳Beijing, Beijing, China
Peking University International Hospital
🇨🇳Beijing, Beijing, China
Daping Hospital, Third Military Medical University
🇨🇳Chongqing, Chongqing, China
The First Affiliated Hospital of Xiamen University
🇨🇳Xiamen, Fujian, China
The First Hospital of Lanzhou University
🇨🇳Lanzhou, Gansu, China
Guangdong Provincial Peoples Hospital
🇨🇳Guangzhou, Guangdong, China
Tianjin Medical University Cancer Institute and Hospital
🇨🇳Tianjin, Tianjin, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Beijing Hospital
🇨🇳Beijing, Beijing, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, Fujian, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Affiliated Hospital of Guilin Medical University
🇨🇳Guilin, Guangxi, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Changsha Central Hospital
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Nanjing Chest Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Jilin Cancer Hospital
🇨🇳Changchun, Jilin, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
Shandong Cancer Hospital
🇨🇳Jinan, Shandong, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, Shandong, China
Shanghai Chest Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
Yunnan Cancer Hospital
🇨🇳Kunming, Yunnan, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China