Clinical Trials /

A Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)

NCT04513925

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: GO41854
  • SECONDARY ID: 2019-004773-29
  • NCT ID: NCT04513925

Conditions

  • Non-small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
AtezolizumabTecentriq; RO5541267Atezolizumab + Tiragolumab
TiragolumabMTIG7192A; RO7092284Atezolizumab + Tiragolumab
DurvalumabDurvalumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab + TiragolumabExperimentalParticipants 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.
  • Atezolizumab
  • Tiragolumab
DurvalumabActive ComparatorParticipants will receive durvalumab administered IV on Days 1 and 15 of each 28-day cycle for a maximum of 13 cycles.
  • Durvalumab

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 (CRT)

          -  At least two prior cycles of platinum-based chemotherapy concurrent with radiotherapy
             (cCRT), which must be completed within 1 to 42 days prior to randomization in the
             study

          -  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

          -  Tumor PD-L1 expression

          -  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

          -  Male participants must remain abstinent or use a condom during the treatment period
             and for 90 days after the final dose of tiragolumab

          -  Male participants must not donate sperm during the treatment period and for 90 days
             after the final dose of tiragolumab

        Exclusion Criteria:

          -  Any history of prior NSCLC

          -  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 concurrent CRT 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

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV
             infection at screening

          -  Treatment with investigational therapy within 28 days prior to initiation of study
             treatment

          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-cytotoxic T lymphocyte-associated protein 4, anti-T-cell immunoreceptor with Ig
             and ITIM domains (anti-TIGIT), anti-PD-1 and anti-PD-L1

          -  Any prior Grade >/= 3 immune-mediated adverse event or any unresolved Grade > 1
             immune-mediated adverse event while receiving any previous immunotherapy agent other
             than immune checkpoint blockade agents

          -  Treatment with systemic immunosuppressive medication

          -  Women who are pregnant, or breastfeeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Independent Review Facility (IRF) Assessed Progression Free Survival (PFS)
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 90 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:From randomization to death from any cause (up to approximately 90 months)
Safety Issue:
Description:
Measure:Investigator-assessed PFS
Time Frame:Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 90 months)
Safety Issue:
Description:
Measure:Confirmed Overall Response Rate (ORR)
Time Frame:From randomization up to approximately 90 months
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 90 months)
Safety Issue:
Description:
Measure:PFS Rates at 12 Months, 18 Months and 24 Months
Time Frame:12, 18 and 24 months
Safety Issue:
Description:
Measure:OS Rates at 12 Months, 24 Months, 36 Months and 48 Months
Time Frame:12, 24, 36 and 48 months
Safety Issue:
Description:
Measure:Time to Death or Distant Metastasis (TTDM)
Time Frame:From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 90 months)
Safety Issue:
Description:
Measure:Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score
Time Frame:Up to approximatley 90 months
Safety Issue:
Description:TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS) and physical functioning from baseline that must be held for all subsequent assessment timepoints or followed by death attributable to cancer progression. 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 quality of life (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.
Measure:Percentage of Participants With Adverse Events
Time Frame:Up to 90 approximately months
Safety Issue:
Description:
Measure:Serum Concentration of Tiragolumab
Time Frame:Pre-dose and post-dose on Day 1 of Cycles 1 and 3 (cycle=28 days) and predose on Day 1 of Cycles 2, 4, 8, 10 and 12 and at treatment discontinuation (TD) visit (up to approximately 90 months)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab
Time Frame:Pre-dose and post-dose on Day 1 of Cycle 1 (cycle=28 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 10 and 12 and at TD visit (up to approximately 90 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
Time Frame:Predose on Day 1 of Cycles 2, 3, 4, 8, 10 and 12 (cycle=28 days) and at TD visit (up to approximately 90 months)
Safety Issue:
Description:
Measure:Percentage of Participants With ADAs to Atezolizumab
Time Frame:Predose on Day 1 of Cycles 2, 3, 4, 8, 10 and 12 (cycle=28 days) and at TD visit (up to approximately 90 months)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

August 13, 2020