Description:
The purpose of this study is to evaluate the efficacy and safety of tiragolumab plus
atezolizumab compared with placebo in participants with unresectable esophageal squamous cell
carcinoma (or those who are unable or unwilling to undergo surgery) and whose cancers have
not progressed following definitive concurrent chemoradiotherapy. 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).
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
Drug | Synonyms | Arms |
---|
Tiragolumab | MTIG7192A, RO7092284 | Arm A: Tiragolumab + Atezolizumab |
Atezolizumab | Tecentriq, RO5541267 | Arm A: Tiragolumab + Atezolizumab |
Tiragolumab Matching Placebo | | Arm B: Tiragolumab Placebo + Atezolizumab |
Atezolizumab Matching Placebo | | Arm 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
Name | Type | Description | Interventions |
---|
Arm A: Tiragolumab + Atezolizumab | Experimental | Participants will receive atezolizumab followed by tiragolumab. | |
Arm B: Tiragolumab Placebo + Atezolizumab | Experimental | Participants will receive atezolizumab followed by tiragolumab matching placebo. | - Atezolizumab
- Tiragolumab Matching Placebo
|
Arm C: Tiragolumab Placebo + Atezolizumab Placebo | Placebo Comparator | Participants 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