Clinical Trials List
Protocol NumberYO42138
NCT Number(ClinicalTrials.gov Identfier)NCT04540211
Active
2020-09-01 - 2026-12-31
Phase III
Recruiting4
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
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Trial Applicant
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Sponsor
Hoffmann-La Roche
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Chueh-Chuan Yen Division of Hematology & Oncology
- 王彥博 Division of General Internal Medicine
- 翁敬堯 Division of Radiology
- 張瀛月 Division of Radiology
- Sheng-Yu Chen Division of Hematology & Oncology
- Yi-Ping Hung Division of Hematology & Oncology
- 陳盛裕 Division of Hematology & Oncology
- Jiun-I Lai Division of Hematology & Oncology
- 李瑩琦 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tai-Jan Chiu Division of Hematology & Oncology
- 吳佳哲 Division of Hematology & Oncology
- 黃詩喻 Division of Hematology & Oncology
- 黃泰霖 Division of Hematology & Oncology
- 陳彥豪 Division of Hematology & Oncology
- 郭明濬 Division of Hematology & Oncology
- Yu-Li Su Division of Hematology & Oncology
- 林偉哲 Division of Radiology
- 賴香蘭 Division of Hematology & Oncology
- 劉建廷 Division of Hematology & Oncology
- 湯禹舜 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 劉奕廷 Division of Hematology & Oncology
- Yau-Lin Tseng Division of Thoracic Surgery
- Wei-Lun Chang Division of General Internal Medicine
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chia-Chi Lin Division of Hematology & Oncology
- Kun-Huei Yeh Division of Hematology & Oncology
- 郭弘揚 未分科
- TA-CHEN HUANG Division of Hematology & Oncology
- JHE-CYUAN GUO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Esophageal Squamous Cell Carcinoma
Objectives
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).
Test Drug
Tiragolumab ；Atezolizumab
Active Ingredient
Tiragolumab ；Atezolizumab
Dosage Form
injection
Dosage
1200mg/20ml ；600mg/10ml
Endpoints
Primary Outcome Measures :
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 Outcome Measures :
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 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) ]
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 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) ]
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.
TTCD in Participant-Reported Dysphagia as Measured by EORTC QLQ-OES18 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) ]
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) [ 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 [ 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) ]
Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab [ Time Frame: 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 [ Time Frame: 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) ]
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 Outcome Measures :
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 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) ]
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 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) ]
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.
TTCD in Participant-Reported Dysphagia as Measured by EORTC QLQ-OES18 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 35 months) ]
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) [ 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 [ 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) ]
Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab [ Time Frame: 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 [ Time Frame: 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) ]
Inclution 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
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
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
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
The Estimated Number of Participants
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Taiwan
42 participants
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Global
450 participants
