A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT04256421
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 490
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Atezolizumab + CE Placebo 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. Tiragolumab + Atezolizumab + CE Atezolizumab 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. Placebo + Atezolizumab + CE Atezolizumab 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. Placebo + Atezolizumab + CE Etoposide 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. Placebo + Atezolizumab + CE Carboplatin 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. Tiragolumab + Atezolizumab + CE Tiragolumab 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. Tiragolumab + Atezolizumab + CE Carboplatin 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. Tiragolumab + Atezolizumab + CE Etoposide 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in the PAS From randomization to death from any cause (up to 50 months) Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months)
- Secondary Outcome Measures
Name Time Method PFS in the Full Analysis Set (FAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) OS in the FAS From randomization to death from any cause (up to 50 months) Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS From randomization up to 50 months Investigator-Assessed Confirmed ORR in the FAS From randomization up to 50 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 50 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 50 months) Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS 6 months, 12 months Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS 6 months, 12 months Overall Survival Rates at 12 Months and 24 Months in the PAS 12 months, 24 months Overall Survival Rates at 12 Months and 24 Months in the FAS 12 months, 24 months Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score in the PAS From randomization until the first confirmed clinically meaningful deterioration up to 50 months TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
TTCD Assessed Using EORTC QLQ-C30 Score in the FAS From randomization until the first confirmed clinically meaningful deterioration up to 50 months TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
Minimum Serum Concentration (Cmin) of Tiragolumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 50 months) Cmin of Atezolizumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Maximum Serum Concentration (Cmax) of Tiragolumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Cmax of Atezolizumab Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) Percentage 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 TD visit (up to 50 months) Percentage 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 50 months) Change from Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Index-based and Visual Analog Scale Scores From baseline up to 50 months The EQ-5D-5L is a validated self-report health status questionnaire that is used to calculate a health status utility score for use in health economic analyses. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analog scale (VAS) that measures health state. A single composite score is calculated based on the responses as an indicator of the participant's health status.
Percentage of Participants With Adverse Events Up to 50 months
Trial Locations
- Locations (118)
Rocky Mountain Cancer Centers - Lone Tree
🇺🇸Lone Tree, Colorado, United States
MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
🇺🇸Washington, District of Columbia, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
SCRI Florida Cancer Specialists North
🇺🇸Sarasota, Florida, United States
Northwest Georgia Oncology Centers PC - Marietta
🇺🇸Marietta, Georgia, United States
Illinois Cancer Care
🇺🇸Peoria, Illinois, United States
New England Cancer Specialists
🇺🇸Scarborough, Maine, United States
Weinberg Cancer Institution at Franklin Square
🇺🇸Baltimore, Maryland, United States
Minnesota Oncology Hematology
🇺🇸Minneapolis, Minnesota, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
Scroll for more (108 remaining)Rocky Mountain Cancer Centers - Lone Tree🇺🇸Lone Tree, Colorado, United States