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
Overview
- Phase
- Phase 3
- Intervention
- Atezolizumab
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 620
- Locations
- 264
- Primary Endpoint
- Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set
- Status
- Completed
- Last Updated
- 3 months ago
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.
Investigators
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
Arms & Interventions
Tiragolumab + Atezolizumab
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.
Intervention: Atezolizumab
Tiragolumab + Atezolizumab
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.
Intervention: Tiragolumab
Placebo + Atezolizumab
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.
Intervention: Atezolizumab
Placebo + Atezolizumab
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.
Intervention: Matching Placebo
Outcomes
Primary Outcomes
Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set
Time Frame: 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
Time Frame: From randomization to death from any cause (up to approximately 59 months)
Percentage of Participants With Adverse Events (AEs)
Time Frame: Up to approximately 59 months
Percentage of Participants With Cytokine-Release Syndrome (CRS)
Time Frame: Up to approximately 59 months
Secondary Outcomes
- 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)
- 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))
- Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score(From randomization until the first confirmed clinically meaningful deterioration (up to approximately 59 months))