A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tiragolumab
* Drug: Atezolizumab
* Drug: Carboplatin
* Drug: Etoposide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo + Atezolizumab + CE<br>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. | Drug: Atezolizumab<br>* Atezolizumab 1200 mg administered by IV infusion on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Carboplatin<br>* Carboplatin was administered by IV infusion on Day 1 of each 21-day cycle for 4 cycles.<br>Drug: Etoposide<br>* Etoposide 100 mg/m^2 administered by IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles.<br>Drug: Placebo<br>* Placebo administered by IV infusion on Day 1 of each 21-day cycle.<br>|
| Experimental: Tiragolumab + Atezolizumab + CE<br>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. | Drug: Tiragolumab<br>* Tiragolumab 600 milligrams (mg) administered by IV infusion on Day 1 of each 21-day cycle.<br>* Other names: MTIG7192A;Drug: Atezolizumab<br>* Atezolizumab 1200 mg administered by IV infusion on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Carboplatin<br>* Carboplatin was administered by IV infusion on Day 1 of each 21-day cycle for 4 cycles.<br>Drug: Etoposide<br>* Etoposide 100 mg/m^2 administered by IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| Overall Survival (OS) in the PAS |  | From randomization to death from any cause (up to 50 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | From randomization until the first confirmed clinically meaningful deterioration up to 50 months | 
| TTCD Assessed Using EORTC QLQ-C30 Score in the FAS | 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. | From randomization until the first confirmed clinically meaningful deterioration up to 50 months | 
| Percentage of Participants With Adverse Events |  | Up to 50 months | 
| 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 | 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. | From baseline up to 50 months |