A Phase III, Open-Label, Randomized Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Patients With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer Who Have Not Progressed After Concurrent Platinum-Based Chemoradiation

Hoffmann-La Roche177 sites in 7 countries829 target enrollmentAugust 24, 2020

ConditionsNon-small Cell Lung Cancer (NSCLC)

InterventionsAtezolizumab Tiragolumab Durvalumab

DrugsAtezolizumab Tiragolumab Durvalumab

Overview

Phase: Phase 3
Intervention: Atezolizumab
Conditions: Non-small Cell Lung Cancer (NSCLC)
Sponsor: Hoffmann-La Roche
Enrollment: 829
Locations: 177
Primary Endpoint: Independent Review Facility (IRF)-assessed Progression Free Survival (PFS) in the PD-L1-positive Analysis Set (PPAS)
Status: Completed
Last Updated: 7 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of atezolizumab in combination with tiragolumab compared with durvalumab in participants with locally advanced, unresectable Stage III non-small cell lung cancer (NSCLC) who have received at least two cycles of concurrent platinum-based chemoradiotherapy (CRT) and have not had radiographic disease progression.

Registry

clinicaltrials.gov

Start Date

August 24, 2020

End Date

July 31, 2025

Last Updated

7 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
•Histologically or cytologically documented NSCLC with locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology
•Whole-body Positron Emission Tomography-Computed Tomography (PET-CT) scan, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (cCRT)
•At least two prior cycles of platinum-based chemotherapy administered concurrently with radiotherapy (RT), which must be completed within 1 to 42 days prior to randomization in the study (one cycle of cCRT is defined as 21 or 28 days)
•The radiotherapy (RT) component in the cCRT must have been at a total dose of radiation of 60 (±10 percent \[%\]) gray (Gy) (54 Gy to 66 Gy) administered by intensity modulated RT (preferred) or 3D-conforming technique
•No progression during or following concurrent platinum-based CRT
•A known PD-L1 result
•Life expectancy \>/= 12 weeks
•Adequate hematologic and end-organ function
•Female participants must be willing to avoid pregnancy for 90 days after the final dose of tiragolumab and 5 months after the final dose of atezolizumab, or for 3 months after the final dose of durvalumab

Exclusion Criteria

•Any history of prior NSCLC and/or any history of prior treatment for NSCLC (participants must be newly diagnosed with unresectable Stage III disease)
•NSCLC known to have a mutation in the epidermal growth factor receptor (EGFR) gene or an anaplastic lymphoma kinase (ALK) fusion oncogene
•Any evidence of Stage IV disease
•Treatment with sequential CRT for locally advanced NSCLC
•Participants with locally advanced NSCLC who have progressed during or after the definitive cCRT prior to randomization
•Any Grade \>2 unresolved toxicity from previous CRT
•Grade \>= 2 pneumonitis from prior CRT
•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
•History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with a negligible risk of metastasis or death

Arms & Interventions

Atezolizumab + Tiragolumab

Participants will receive atezolizumab administered intravenously (IV) on Day 1 of each 28-day cycle followed by tiragolumab administered IV on Day 1 of each 28-day cycle for a maximum of 13 cycles.

Intervention: Atezolizumab

Atezolizumab + Tiragolumab

Participants will receive atezolizumab administered intravenously (IV) on Day 1 of each 28-day cycle followed by tiragolumab administered IV on Day 1 of each 28-day cycle for a maximum of 13 cycles.

Intervention: Tiragolumab

Durvalumab

Participants will receive durvalumab administered IV during each 28-day cycle for a maximum of 13 cycles.

Intervention: Durvalumab

Outcomes

Primary Outcomes

Independent Review Facility (IRF)-assessed Progression Free Survival (PFS) in the PD-L1-positive Analysis Set (PPAS)

Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months)

IRF-assessed PFS in the Full Analysis Set (FAS)

Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months)

Secondary Outcomes

Investigator-assessed PFS in the PPAS(Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months))
IRF-assessed Confirmed Objective Response Rate (ORR) in the PPAS(From randomization up to approximately 114 months)
IRF-assessed Duration of Response (DOR) in the PPAS(From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months))
Overall Survival (OS) in the PPAS(From randomization to death from any cause (up to approximately 114 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 PPAS(Up to approximately 114 months)
TTCD Assessed Using EORTC QLQ-C30 Score in the FAS(Up to approximately 114 months)
OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the FAS(12, 24, 36 and 48 months)
Investigator-assessed Confirmed ORR in the PPAS(From randomization up to approximately 114 months)
OS in the FAS(From randomization to death from any cause (up to approximately 114 months))
Investigator-assessed DOR in the PPAS(From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months))
Investigator-assessed PFS in the FAS(Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months))
IRF-assessed DOR in the FAS(From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months))
IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS(12, 18 and 24 months)
IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS(12, 18 and 24 months)
OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the PPAS(12, 24, 36 and 48 months)
Investigator-assessed Time to Death or Distant Metastasis (TTDM) in the PPAS(From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months))
Percentage of Participants With Adverse Events(Up to approximately 114 months)
IRF-assessed Confirmed ORR in the FAS(From randomization up to approximately 114 months)
Investigator-assessed Confirmed ORR in the FAS(From randomization up to approximately 114 months)
Investigator-assessed DOR in the FAS(From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months))
Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS(12, 18 and 24 months)
Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS(12, 18 and 24 months)
Investigator-assessed TTDM in the FAS(From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months))