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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

Phase 3
Active, not recruiting
Conditions
Non-Small Cell Lung Cancer
Interventions
Registration Number
NCT04294810
Lead Sponsor
Hoffmann-La Roche
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
620
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Tiragolumab + AtezolizumabAtezolizumabParticipants 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.
Placebo + AtezolizumabAtezolizumabParticipants 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.
Tiragolumab + AtezolizumabTiragolumabParticipants 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.
Placebo + AtezolizumabMatching PlaceboParticipants 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.
Primary Outcome Measures
NameTimeMethod
Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis SetFrom 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 SetFrom 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
NameTimeMethod
OS in the Secondary Analysis SetFrom 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 Months6 months, 12 months
OS Rates at 12 Months and 24 Months12 months, 24 months
Investigator-Assessed PFS in the Secondary Analysis SetFrom 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) ScoreFrom randomization until the first confirmed clinically meaningful deterioration (up to approximately 59 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.

Trial Locations

Locations (140)

Rocky Mountain Cancer Center - Denver

🇺🇸

Denver, Colorado, United States

Yale Cancer Center

🇺🇸

New Haven, Connecticut, United States

SCRI Florida Cancer Specialists North

🇺🇸

Saint Petersburg, Florida, United States

SCRI Florida Cancer Specialists PAN

🇺🇸

Tallahassee, Florida, United States

US oncology research at Minnesota Oncology

🇺🇸

Saint Paul, Minnesota, United States

SCRI Oncology Partners

🇺🇸

Nashville, Tennessee, United States

Virginia Cancer Specialists (Fairfax) - USOR

🇺🇸

Fairfax, Virginia, United States

Onc & Hem Assoc SW Virginia

🇺🇸

Salem, Virginia, United States

Northwest Cancer Specialists - Vancouver

🇺🇸

Vancouver, Washington, United States

Princess Alexandra Hospital

🇦🇺

Woolloongabba, Queensland, Australia

Scroll for more (130 remaining)
Rocky Mountain Cancer Center - Denver
🇺🇸Denver, Colorado, United States

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