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

Hoffmann-La Roche620 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

620

Conditions

Non-Small Cell Lung Cancer

Interventions

Atezolizumab

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (134)

Rocky Mountain Cancer Center - Denver

Denver, Colorado, United States

Yale Cancer Center

New Haven, Connecticut, United States

SCRI Florida Cancer Specialists North

St. Petersburg, Florida, United States

SCRI Florida Cancer Specialists PAN

Tallahassee, Florida, United States

US oncology research at Minnesota Oncology

Saint Paul, Minnesota, United States

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

Investigator-Assessed PFS in the Secondary 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)

OS in the Secondary Analysis Set

Time frame: From randomization to death from any cause (up to approximately 59 months)

Investigator-Assessed Confirmed Objective Response Rate (ORR)

Time frame: From randomization up to approximately 59 months

Investigator-Assessed Duration of Response (DOR)

Time frame: 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

Time frame: 6 months, 12 months

OS Rates at 12 Months and 24 Months

Time frame: 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.

Time frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 59 months)