Esophageal Squamous Cell Carcinoma
Conditions
Brief summary
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 (dCRT). 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).
Interventions
DRUGTiragolumab
Tiragolumab at a fixed dose of 600 milligrams (mg) administered by intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
DRUGAtezolizumab
Atezolizumab at a fixed dose of 1200 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Tiragolumab matching placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Atezolizumab matching placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 disease ineligible for curative surgery based on the documented opinion of the qualified medical, surgical or radiation oncologist prior to dCRT and is not expected to undergo tumor resection during the course of the study * dCRT treatment according to regional oncology guidelines for esophageal cancer * Representative archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens collected prior to initiation of dCRT * Adequate hematologic and end-organ function prior to randomization * Women of childbearing potential must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period, for 5 months after the final dose of atezolizumab/placebo, and for 90 days after the final dose of tiragolumab/placebo, whichever is later * Men must agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for 90 days after the final dose of tiragolumab/placebo. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Arm A vs Arm C: Investigator-Assessed Progression-Free Survival (PFS) | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) |
| Arm A vs Arm C: Overall Survival (OS) | From randomization to death from any cause (up to approximately 6 years) |
| Arm B vs Arm C: OS | From randomization to death from any cause (up to approximately 6 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arm B vs Arm C: Investigator-Assessed PFS | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) | — |
| Arm A vs Arm B: Investigator-Assessed PFS | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) | — |
| Arm A vs Arm B: OS | From randomization to death from any cause (up to approximately 6 years) | — |
| Independent Review Facility (IRF)-Assessed PFS | From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 6 years) | — |
| Investigator-Assessed Confirmed Objective Response Rate (ORR) | From randomization up to approximately 6 years | — |
| IRF-Assessed Confirmed ORR | From randomization up to approximately 6 years | — |
| Investigator-Assessed Duration of Objective Response (DOR) | 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 6 years) | — |
| IRF-Assessed DOR | 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 6 years) | — |
| Percentage of Participants With Clinically Meaningful Changes in Physical Functioning, Role Functioning, Quality of Life (QoL) as Measured by EORTC QLQ-C30 | Up to approximately 6 years | 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. |
| Percentage of Participants With Clinically Meaningful Changes in Dysphagia as Measured by EORTC QLQ-OES18 | Up to approximately 6 years | 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. |
| Percentage of Participants With Adverse Events (AEs) | Up to approximately 6 years | — |
| Serum Concentration of Tiragolumab | 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 6 years) | — |
| Serum Concentration of Atezolizumab | 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 6 years) | — |
| Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab | 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 6 years) | — |
| Percentage of Participants With ADAs to Atezolizumab | 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 6 years) | — |
Countries
Argentina, Australia, Austria, Belgium, China, France, Germany, Greece, Hungary, Israel, Italy, Japan, Kenya, Morocco, New Zealand, Poland, Portugal, Russia, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trial
Hoffmann-La Roche
Outcome results
None listed