A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab (Anti-Tigit Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 490
- 试验地点
- 193
- 主要终点
- Investigator-assessed Progression-free Survival (PFS) in the Primary Analysis Set (PAS)
研究概览
简要总结
This study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), LDH (</= upper limit of normal [ULN] vs. > ULN), and presence or history of brain metastasis (yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment regimens during induction phase:
- Arm A: Tiragolumab plus atezolizumab plus CE
- Arm B: Placebo plus atezolizumab plus CE
Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC)
- •No prior systemic treatment for ES-SCLC
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- •Adequate hematologic and end-organ function
- •Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC
排除标准
- •Symptomatic or actively progressing central nervous system (CNS) metastases
- •Malignancies other than small cell lung cancer (SCLC) within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- •Positive test result for human immunodeficiency virus (HIV)
- •Active hepatitis B or hepatitis C
- •Severe infection at the time of randomization
- •Treatment with any other investigational agent within 28 days prior to initiation of study treatment
- •Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4), anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- •Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to randomization
研究组 & 干预措施
Placebo + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Placebo (Drug)
Placebo + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Atezolizumab (Drug)
Placebo + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Etoposide (Drug)
Placebo + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Carboplatin (Drug)
Tiragolumab + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Tiragolumab (Drug)
Tiragolumab + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Atezolizumab (Drug)
Tiragolumab + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Carboplatin (Drug)
Tiragolumab + Atezolizumab + CE
Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
干预措施: Etoposide (Drug)
结局指标
主要结局
Investigator-assessed Progression-free Survival (PFS) in the Primary Analysis Set (PAS)
时间窗: From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months)
PFS was defined as the time from randomization to the first documented PD as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm).
Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS)
时间窗: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months)
PFS was defined as the time from randomization to the first documented disease progression (PD) as determined by the investigator with the use of Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first. PD: at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD on study (including baseline). In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
Overall Survival (OS) in the PAS
时间窗: From randomization to death from any cause (up to approximately 24 months)
OS was defined as the time from randomization to death from any cause.
次要结局
- Investigator-assessed Duration of Response (DOR) in the PAS(From the first occurrence of a documented confirmed objective response (OR) to PD or death from any cause, whichever occurred first (up to approximately 24 months))
- PFS in the FAS(From randomization to the first occurrence of PD or death from any cause, whichever occurred first (up to approximately 24 months))
- Investigator-assessed Confirmed Objective Response Rate (ORR) in the PAS(From randomization up to approximately 24 months)
- Investigator-assessed Confirmed ORR in the FAS(From randomization up to approximately 24 months)
- Investigator-assessed DOR in the FAS(From the first occurrence of a documented confirmed OR to PD or death from any cause, whichever occurred first (up to approximately 24 months))
- Investigator-assessed PFS Rates at 6 Months and 12 Months in the PAS(Month 6, Month 12)
- Investigator-assessed PFS Rates at 6 Months and 12 Months in the FAS(Month 6, Month 12)
- OS Rates at 12 Months and 24 Months in the PAS(Month 12, Month 24)
- OS Rates at 12 Months and 24 Months in the FAS(Month 12, Month 24)
- Time to Confirmed Deterioration (TTCD) of European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (PF) in the PAS(From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months))
- TTCD of EORTC QLQ-C30 Physical Functioning in the FAS(From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months))
- TTCD of EORTC QLQ-C30 Global Health Status (GHS)/Quality-of-life (QoL) in the PAS(From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months))
- TTCD of EORTC QLQ-C30 GHS/QoL in the FAS(From randomization until the first confirmed clinically meaningful deterioration (up to approximately 24 months))
- Number of Participants With Adverse Events (AEs)(Up to 58 months)
- Number of Participants With Severity of Cytokine-release Syndrome (CRS), as Determined by the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Scale(Up to 58 months)
- Minimum Serum Concentration (Cmin) of Tiragolumab(At the end of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days))
- Cmin of Atezolizumab(At the end of each Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months) (1 Cycle=21 days))
- Maximum Serum Concentration (Cmax) of Tiragolumab(Pre-dose and 30 minutes post end of infusion (EOI) on Day 1 of Cycle 1 (1 Cycle=21 days))
- Cmax of Atezolizumab(Pre-dose and 30 minutes post EOI on Day 1 of Cycle 1 (1 Cycle=21 days))
- Number of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab(Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8,12, 16 and at treatment discontinuation (TD) visit (up to 24 months) (1 Cycle=21 days))
- Number of Participants With ADAs to Atezolizumab(Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8,12, 16 and at TD visit (up to 24 months) (1 Cycle=21 days))
- PFS in the FAS(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 24 months))
- OS in the FAS(From randomization to death from any cause (up to approximately 24 months))
- Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS(From randomization up to approximately 24 months)
- Investigator-Assessed Confirmed ORR in the FAS(From randomization up to approximately 24 months)
- Investigator-Assessed Duration of Response (DOR) in the PAS(From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to approximately 24 months))
- Investigator-Assessed DOR in the FAS(From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to approximately 24 months))
- Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS(Month 6, Month 12)
- Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS(Month 6, Month 12)
- Overall Survival Rates at 12 Months and 24 Months in the PAS(Month 12, Month 24)
- Overall Survival Rates at 12 Months and 24 Months in the FAS(Month 12, Month 24)
- Time to Confirmed Deterioration (TTCD) of European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Physical Functioning in the PAS(From randomization until the first confirmed clinically meaningful deterioration up to approximately 24 months)
- TTCD of EORTC QLQ-C30 Physical Functioning in the FAS(From randomization until the first confirmed clinically meaningful deterioration up to approximately 24 months)
- TTCD of EORTC QLQ-C30 Global Health Status (GHS)/Quality of Life (QoL) in the PAS(From randomization until the first confirmed clinically meaningful deterioration up to approximately 24 months)
- TTCD of EORTC QLQ-C30 GHS/QoL in the FAS(From randomization until the first confirmed clinically meaningful deterioration up to 24 months)
- Percentage of Participants With Adverse Events(Up to 65 months)
- Minimum Serum Concentration (Cmin) of Tiragolumab(At the end of each cycle (each cycle is 21 days) of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months))
- Cmin of Atezolizumab(At the end of each cycle (each cycle is 21 days) of Cycles 1, 2, 3, 7, 11 and 15 (approximately 11 months))
- Maximum Serum Concentration (Cmax) of Tiragolumab(Predose and 30 minutes post end of infusion (EOI) on Day 1 of Cycle 1 (each cycle is 21 days))
- Cmax of Atezolizumab(Predose and 30 minutes post EOI on Day 1 of Cycle 1 (each cycle is 21 days))
- Number of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab(Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 24 months))
- Number of Participants With ADAs to Atezolizumab(Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 24 months))
- Change From Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Index-based and Visual Analog Scale Scores(From baseline up to 65 months)