Esophageal squamous cell carcinoma MedDRA version: 21.0 Level: LLT Classification code 10055476 Term: Esophageal squamous cell carcinoma System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >=18 years • Eastern Cooperative Oncology Group 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 and is not expected to undergo tumor resection during the course of the study • Definitive concurrent chemoradiation treatment (dCRT) according to regional oncology guidelines for esophageal cancer • Representative archival formalin-fixed, paraffin-embedded tumor specimens, collected prior to initiation of dCRT • Adequate hematologic and end-organ function • Women of childbearing potential must remain abstinent or use contraceptive methods with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 465
Exclusion criteria
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 Common Terminology Criteria for Adverse Events, Version 5.0 (NCI 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 • Malignancy 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 EGFR inhibitors, with therapeutic intent for esophageal cancer prior to randomization • Severe infection within 4 weeks prior to randomization, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact patient safety.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of tiragolumab+atezolizumab compared with double placebo based on investigator assessed progression free survival (PFS) and overall survival (OS) • To evaluate the efficacy of placebo+atezolizumab compared with double placebo based on investigator assessed OS.;Secondary Objective: • To evaluate the efficacy of placebo+atezolizumab compared with double placebo on the basis of investigator and IRF assessed progression-free survival • To evaluate the efficacy of tiragolumab+atezolizumab versus placebo+atezolizumab to demonstrate the contribution of tiragolumab • To evaluate the efficacy of tiragolumab+atezolizumab and placebo+atezolizumab compared with double placebo and the efficacy of tiragolumab+atezolizumab versus placebo+atezolizumab to demonstrate the contribution of tiragolumab • To evaluate safety and tolerability of tiragolumab+atezolizumab and placebo+atezolizumab compared with double placebo • To characterize pharmacokinetics of tiragolumab and atezolizumab • To evaluate immune response to tiragolumab and atezolizumab.;Primary end point(s): 1. Progression-Free Survival as determined by the investigator (for tiragolumab+atezolizumab compared with double placebo) 2. Overall survival (for tiragolumab+atezolizumab compared with double placebo) 3. Overall Survival (for placebo+atezolizumab compared with double placebo).;Timepoint(s) of evaluation of this end point: 1-3. Up to approximately 50 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1- 8. Up to approximately 50 months 9. Day 1 of Cycle 1 and Day 1 of every cycle thereafter until treatment discontinuation, and at the study treatment discontinuation visit and during survival follow-up, every 3 months for 1 year 10. Up to approximately 50 months 11-13. Day 1 of Cycle 1, Day 1 of Cycle 2-4, 8, 12, 16 and at treatment discontinuation, disease progression, or completion visit.;Secondary end point(s): 1. Progression-Free Survival as determined by the investigator (for placebo+atezolizumab compared with double placebo) 2. Progression-Free Survival as determined by the investigator (for tiragolumab+atezolizumab compared with placebo+atezolizumab) 3. Overall Survival (for tiragolumab+atezolizumab compared with placebo+atezolizumab) 4. Progression-Free Survival as determined by the independent review facility (IRF) 5. Confirmed ORR as determined by the investigator 6. Confirmed ORR as determined by an IRF 7. Duration of response as determined by the investigator 8. Duration of response as determined by the IRF 9. Proportion of patients with clinically meaningful changes in physical functioning, role functioning, global health status/quality of life, and dysphagia, as measured by the respective scales of the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire and the European Organisation for Research and Treatment of Cancer Quality of Life-Esophageal Cancer, Module 18 Questionnaire 10. Incidence and severity of adverse events 11. Serum concentration of tiragolumab and atezolizumab at specified timepoints 12. Prevalence of anti-drug antibody (ADAs) to tiragolumab at baseline and incidence of ADAs to tiragolumab during the study 13. Prevalence of ADAs to atezolizumab at baseline and incidence of ADAs to atezolizumab during the study. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Kenya, Korea, Republic of, Morocco, New Zealand, Poland, Portugal, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
Genentech Inc. c/o F. Hoffmann-La Roche Ltd
Outcome results
None listed