A Study of Atezolizumab Plus Tiragolumab in Combination With Paclitaxel and Cisplatin Compared With Paclitaxel and Cisplatin as First-Line Treatment in Participants With Unresectable Locally Advanced, Unresectable Recurrent, or Metastatic Esophageal Carcinoma

Hoffmann-La Roche461 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

461

Conditions

Esophageal Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key 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 Key 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 * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-CTLA-4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies * Treatment with any investigational therapy prior to initiation of study treatment * Poor peripheral venous access * Prior allogeneic stem cell or solid organ transplantation * Concurrent participation in another therapeutic clinical trial

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 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)

IRF-Assessed Confirmed Objective Response Rate (ORR)

Time frame: From randomization up to approximately 35 months

Investigator-Assessed Confirmed ORR

Time frame: From randomization up to approximately 35 months

IRF-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 35 months)

Investigator-Assessed DOR

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

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.

Time frame: 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

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.

Time frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months)

Percentage of Participants With Adverse Events (AEs)

Time frame: Up to approximately 35 months

Minimum Serum Concentration (Cmin) of Tiragolumab

Time frame: 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

Time frame: 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

Time frame: 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