Clinical Trials /

A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

NCT04543617

Description:

The purpose of this study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo in participants with unresectable locally advanced esophageal squamous cell carcinoma and who have completed definitive concurrent chemoradiation therapy. Participants will be randomized in a 1:1:1 ratio to receive either tiragolumab plus atezolizumab (Arm A), tiragolumab matching placebo plus atezolizumab (Arm B), or double placebo (Arm C).

Related Conditions:
  • Esophageal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab With or Without Tiragolumab in Participants With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma
  • Official Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab With or Without Tiragolumab (Anti-TIGIT Antibody), in Patients With Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: YO42137
  • SECONDARY ID: 2020-001178-31
  • NCT ID: NCT04543617

Conditions

  • Esophageal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
TiragolumabMTIG7192A, RO7092284Arm A: Tiragolumab + Atezolizumab
AtezolizumabTecentriq, RO5541267Arm A: Tiragolumab + Atezolizumab
Tiragolumab Matching PlaceboArm B: Tiragolumab Placebo + Atezolizumab
Atezolizumab Matching PlaceboArm C: Tiragolumab Placebo + Atezolizumab Placebo

Purpose

The purpose of this study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo in participants with unresectable locally advanced esophageal squamous cell carcinoma and who have completed definitive concurrent chemoradiation therapy. Participants will be randomized in a 1:1:1 ratio to receive either tiragolumab plus atezolizumab (Arm A), tiragolumab matching placebo plus atezolizumab (Arm B), or double placebo (Arm C).

Trial Arms

NameTypeDescriptionInterventions
Arm A: Tiragolumab + AtezolizumabExperimentalParticipants will receive atezolizumab followed by tiragolumab.
  • Tiragolumab
  • Atezolizumab
Arm B: Tiragolumab Placebo + AtezolizumabExperimentalParticipants will receive atezolizumab followed by tiragolumab matching placebo.
  • Atezolizumab
  • Tiragolumab Matching Placebo
Arm C: Tiragolumab Placebo + Atezolizumab PlaceboPlacebo ComparatorParticipants will receive matching placebos to tiragolumab and atezolizumab.
  • Tiragolumab Matching Placebo
  • Atezolizumab Matching Placebo

Eligibility Criteria

        Key Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of the
             esophagus

          -  Unresectable locally advanced disease

          -  Definitive concurrent chemoradiation treatment according to regional oncology
             guidelines for esophageal cancer

          -  Representative archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens,
             collected prior to initiation of definitive chemoradiotherapy

          -  Adequate hematologic and end-organ function

          -  Female participants must be willing to avoid pregnancy and refrain from donating eggs
             during the treatment period and for 90 days after the final dose

          -  Male participants with partners of childbearing potential must commit to the use of
             two methods of contraception and must not donate sperm for the study duration and 90
             days after the final dose

        Key Exclusion Criteria:

          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-TIGIT therapeutic antibodies

          -  Any unresolved toxicity of National Cancer Institute's (NCI) Common Terminology
             Criteria for Adverse Events (CTCAE) Grade ≥ 2 from the prior chemoradiation therapy
             with the exception of irreversible and manageable hearing loss

          -  Prior allogeneic stem cell or solid organ transplantation

          -  Active or history of autoimmune disease or immune deficiency

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
             active pneumonitis

          -  Malignancies other than esophageal cancer within 2 years prior to screening, with the
             exception of malignancies with a negligible risk of metastasis or death

          -  Treatment with any other investigational agent, including epidermal growth factor
             receptor (EGFR) inhibitors, with therapeutic intent for esophageal cancer prior to
             randomization
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Arm A vs Arm C: Investigator-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 50 months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Arm B vs Arm C: Investigator-Assessed PFS
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months)
Safety Issue:
Description:
Measure:Arm A vs Arm B: Investigator-Assessed PFS
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months)
Safety Issue:
Description:
Measure:Arm A vs Arm B: OS
Time Frame:From randomization to death from any cause (up to approximately 50 months)
Safety Issue:
Description:
Measure:Independent Review Facility (IRF)-Assessed PFS
Time Frame:From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months)
Safety Issue:
Description:
Measure:Investigator-Assessed Confirmed Objective Response Rate (ORR)
Time Frame:From randomization up to approximately 50 months
Safety Issue:
Description:
Measure:IRF-Assessed Confirmed ORR
Time Frame:From randomization up to approximately 50 months
Safety Issue:
Description:
Measure:Investigator-Assessed Duration of Objective Response (DOR)
Time Frame:From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months)
Safety Issue:
Description:
Measure:IRF-Assessed DOR
Time Frame:From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 50 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Clinically Meaningful Changes in Physical Functioning, Role Functioning, Quality of Life (QoL) as Measured by EORTC QLQ-C30
Time Frame:Up to approximately 50 months
Safety Issue:
Description:Clinically meaningful changes in physical functioning, role functioning, global health status (GHS)/QoL as measured by the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30). EORTC QLQ-C30 is 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) within the previous week. Functioning and symptoms items are scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. GHS and QoL items are scored on a 7-point scale: 1=Very poor, 2, 3, 4, 5, 6, 7=Excellent. Scores will be linearly transformed to a range of 0 to 100, with higher scores (i.e. closer to 100) reflecting better functioning, better GHS/QoL, and worse symptoms.
Measure:Percentage of Participants With Clinically Meaningful Changes in Dysphagia as Measured by EORTC QLQ-OES18
Time Frame:Up to approximately 50 months
Safety Issue:
Description:Clinically meaningful changes in dysphagia as measured by the EORTC Quality of Life-Esophageal Cancer, Module 18 Questionnaire (EORTC QLQ-OES18). EORTC QLQ-OES18 is a modular supplement to the EORTC QLQ-C30 questionnaire for use in participants with esophageal cancer. EORTC QLQ-OES18 consists of 4 multiple-item scale (dysphagia, eating, reflux, and pain) and 6 single items (trouble swallowing saliva, choked when swallowing, dry mouth, trouble with taste, trouble with coughing, and trouble talking) with a recall period of the previous week. Each symptom item is scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores will be linearly transformed to a range of 0 to 100, with higher transformed scores (i.e. closer to 100) reflecting worse symptoms.
Measure:Percentage of Participants With Adverse Events (AEs)
Time Frame:Up to approximately 50 months
Safety Issue:
Description:
Measure:Serum Concentration of Tiragolumab
Time Frame:Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at treatment discontinuation (TD) visit (up to approximately 50 months)
Safety Issue:
Description:
Measure:Serum Concentration of Atezolizumab
Time Frame:Predose and postdose on Day 1 of Cycle 1 (each cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 50 months)
Safety Issue:
Description:
Measure:Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab
Time Frame:Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 50 months)
Safety Issue:
Description:
Measure:Percentage of Participants With ADAs to Atezolizumab
Time Frame:Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 50 months)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

September 3, 2020