Phase 3
N=461
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
Esophageal Cancer
Bottom Line
View on ClinicalTrials.gov: NCT04540211 ↗Enrolled (actual)
461
Serious AEs
40.2%
Results posted
Apr 2026
Primary outcome: Primary: Independent Review Facility (IRF)-Assessed Progression-Free Survival (PFS) — 5.39; 6.18 months — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Atezolizumab (Drug); Tiragolumab (Drug); Paclitaxel (Drug); Cisplatin (Drug); Atezolizumab Matching Placebo (Drug); Tiragolumab Matching Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Feb 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Independent Review Facility (IRF)-Assessed Progression-Free Survival (PFS) |
5.39; 6.18 | <0.0001 sig |
| PRIMARY Overall Survival (OS) |
11.10; 15.74 | 0.0024 sig |
| SECONDARY Investigator-Assessed PFS |
5.45; 7.00 | <0.0001 sig |
| SECONDARY IRF-Assessed Confirmed Objective Response Rate (ORR) |
45.5; 59.7 | 0.0025 sig |
| SECONDARY Investigator-Assessed Confirmed ORR |
41.4; 55.9 | 0.0017 sig |
| SECONDARY IRF-Assessed Duration of Objective Response (DOR) |
4.34; 7.10 | — |
| SECONDARY Investigator-Assessed DOR |
5.78; 8.31 | — |
| SECONDARY Time to Confirmed Deterioration (TTCD) in Participant-Reported Physical Functioning as Measured by EORTC QLQ-C30 |
15.80; 16.10 | 0.6068 |
| SECONDARY TTCD in Participant-Reported Role Functioning as Measured by EORTC QLQ-C30 |
NA; 15.11 | 0.1143 |
| SECONDARY TTCD in Participant-Reported Global Health Status (GHS)/Quality of Life (QoL) as Measured by EORTC QLQ-C30 |
18.20; NA | 0.1096 |
| SECONDARY TTCD in Participant-Reported Dysphagia as Measured by EORTC Quality of Life-Esophageal Cancer, Module 18 Questionnaire (EORTC QLQ-OES18) |
12.35; NA | 0.2795 |
| SECONDARY Percentage of Participants With Adverse Events (AEs) |
— | — |
| SECONDARY Minimum Serum Concentration (Cmin) of Tiragolumab |
— | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Tiragolumab |
— | — |
| SECONDARY Cmin of Atezolizumab |
— | — |
| SECONDARY Cmax of Atezolizumab |
— | — |
| SECONDARY Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab |
— | — |
| SECONDARY Number of Participants Positive for ADAs to Atezolizumab |
— | — |
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).
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT04540211). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.