A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Patients With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma
Overview
- Phase
- Phase 3
- Intervention
- Atezolizumab
- Conditions
- Esophageal Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 461
- Locations
- 64
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 6 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of atezolizumab plus tiragolumab in combination with paclitaxel and cisplatin (PC) compared with atezolizumab matching placebo plus tiragolumab matching placebo plus PC as first-line treatment in participants with unresectable locally advanced, unresectable recurrent, or metastatic esophageal carcinoma (EC). Participants will be randomized in a 1:1 ratio to receive one of the following treatment regimens during induction phase:
Arm A: Atezolizumab plus Tiragolumab and PC Arm B: Atezolizumab placebo plus Tiragolumab placebo and PC Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab matching placebo plus tiragolumab matching placebo (Arm B).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed EC
- •Unresectable locally advanced, unresectable recurrent, or metastatic disease
- •Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •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
Exclusion Criteria
- •Palliative radiation treatment for EC within 4 weeks prior to initiation of study treatment
- •Evidence of complete esophageal obstruction not amenable to treatment
- •Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- •Uncontrolled tumor-related pain, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- •Active or history of autoimmune disease or immune deficiency or leptomeningeal disease
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis
- •Malignancies other than EC within 2 years prior to screening with a negligible risk of metastasis or death adequately treated with expected curative outcome
- •Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
- •Positive test result for human immunodeficiency virus (HIV)
- •Active hepatitis B or hepatitis C
Arms & Interventions
Atezolizumab + Tiragolumab + PC
Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Atezolizumab
Atezolizumab + Tiragolumab + PC
Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Tiragolumab
Atezolizumab + Tiragolumab + PC
Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Paclitaxel
Atezolizumab + Tiragolumab + PC
Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Cisplatin
Placebo + PC
Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Paclitaxel
Placebo + PC
Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Cisplatin
Placebo + PC
Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Atezolizumab Matching Placebo
Placebo + PC
Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase.
Intervention: Tiragolumab Matching Placebo
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: From randomization to death from any cause (up to approximately 35 months)
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 35 months)
Secondary Outcomes
- Investigator-Assessed Confirmed ORR(From randomization up to approximately 35 months)
- Investigator-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 35 months))
- IRF-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 35 months))
- Investigator-Assessed PFS(From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 35 months))
- IRF-Assessed Confirmed Objective Response Rate (ORR)(From randomization up to approximately 35 months)
- Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning, Role Functioning and Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30(From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months))
- TTCD in Participant-Reported Dysphagia as Measured by EORTC QLQ-OES18(From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months))
- Percentage of Participants With Adverse Events (AEs)(Up to approximately 35 months)
- Minimum Serum Concentration (Cmin) of Tiragolumab(Cycle 1 (cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 35 months))
- Maximum Serum Concentration (Cmax) of Tiragolumab(Cycle 1 (cycle=21 days), Day 1: predose, 0.5h postdose; Cycles 2, 3, 4, 8, 12, 16: Day 1: predose and at TD visit (up to approximately 35 months))
- Cmin of Atezolizumab(Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months))
- Cmax of Atezolizumab(Cycle 1 (cycle=21 days): Day 1 (predose, 0.5 h postdose); Cycles 2, 3, 4, 8, 12, 16: Day 1 (predose) and at TD visit (up to approximately 35 months))
- Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab(Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months))
- Percentage of Participants With ADAs to Atezolizumab(Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8, 12 and 16 and at TD visit (up to approximately 35 months))