A Study of Tiragolumab in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in participants with previously untreated locally advanced, unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), with no epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. Eligible participants will be randomized in a 1:1 ratio to receive either tiragolumab plus atezolizumab or placebo plus atezolizumab.

Official Title
-----------------
A Phase III, Randomized, Double-Blinded, Placebo-Controlled Study of Tiragolumab, an Anti-Tigit Antibody, in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer

Conditions
-----------------
Non-Small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: Atezolizumab
* Drug: Tiragolumab
* Drug: Matching Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Histologically or cytologically documented locally advanced or recurrent NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, or metastatic Stage IV non-squamous or squamous NSCLC No prior systemic treatment for metastatic NSCLC High tumor tissue PD-L1 expression Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) Adequate hematologic and end-organ function For participants enrolled in the extended China enrollment phase: current resident of mainland China or Taiwan and of Chinese ancestry. Exclusion Criteria: Known mutation in the EGFR gene or an ALK fusion oncogene Symptomatic, untreated, or actively progressing central nervous system metastases 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 Malignancies other than NSCLC within 5 years, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome Severe infection within 4 weeks prior to initiation of study treatment Positive test result for human immunodeficiency virus (HIV) Active hepatitis B or hepatitis C Treatment with investigational therapy within 28 days prior to initiation of study treatment Prior treatment with CD137 agonists or immune checkpoint blockade therapies, 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 initiation of study treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiragolumab + Atezolizumab<br>Participants will receive atezolizumab followed by tiragolumab every 3 weeks (Q3W) on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity. | Drug: Atezolizumab<br>* Atezolizumab 1200 milligrams (mg) administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Tiragolumab<br>* Tiragolumab 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: MTIG7192A;|
| Placebo Comparator: Placebo + Atezolizumab<br>Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity. | Drug: Atezolizumab<br>* Atezolizumab 1200 milligrams (mg) administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.<br>* Other names: Tecentriq;Drug: Matching Placebo<br>* Matching Placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set |  | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 59 months) | 
| Overall Survival (OS) in the Primary Analysis Set |  | From randomization to death from any cause (up to approximately 59 months) | 
| Percentage of Participants With Adverse Events (AEs) |  | Up to approximately 59 months | 
| Percentage of Participants With Cytokine-Release Syndrome (CRS) |  | Up to approximately 59 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-Assessed PFS in the Secondary Analysis Set |  | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 59 months) | 
| OS in the Secondary Analysis Set |  | From randomization to death from any cause (up to approximately 59 months) | 
| Investigator-Assessed Confirmed Objective Response Rate (ORR) |  | From randomization up to approximately 59 months | 
| Investigator-Assessed Duration of Response (DOR) |  | From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first (up to approximately 59 months) | 
| Investigator-Assessed PFS Rates at 6 Months and 12 Months |  | 6 months, 12 months | 
| OS Rates at 12 Months and 24 Months |  | 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 | 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 approximately 59 months) |