A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma

Phase 3

Completed

• Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
• Interventions: Drug: Tislelizumab; Drug: Paclitaxel; Drug: Docetaxel; Drug: Irinotecan

• Registration Number: NCT03430843
• Lead Sponsor: BeiGene

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of tislelizumab as second line treatment in participants with advanced unresectable/metastatic ESCC that had progressed during or after first line therapy.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-01-26
• Study First Submitted: 2018-01-29
• Study First Submitted QC: 2018-02-06
• Study First Posted: 2018-02-13
• Primary Completion: 2020-12-01
• Disposition First Submitted: 2021-11-23
• Study Completion: 2022-12-28
• Results First Submitted: 2023-11-10
• Results First Submitted QC: 2023-12-12
• Results First Posted: 2023-12-29
• Disposition First Posted: 2023-12-29
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-23
• Last Update Posted: 2024-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 512

Inclusion Criteria

1. Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC)
2. Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC
3. At least one measurable/evaluable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization

Key

Exclusion Criteria

1. Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC
2. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization
3. Tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator
4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
5. Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)
6. Prior malignancy active within the previous 2 years (exceptions include the tumor under investigation in this trial, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast)
7. Active brain or leptomeningeal metastasis.
8. Has active autoimmune disease or history of autoimmune diseases at high risk for relapse
9. Known history of, or any evidence of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases, etc
10. Known history of Human Immunodeficiency Virus (HIV)
11. Has cardiovascular risk factors
12. Pregnant or breastfeeding woman.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tislelizumab	Tislelizumab	Tislelizumab on Day 1, given every 21 days
Investigator chosen chemotherapy (ICC)	Paclitaxel	Paclitaxel on Day 1, given every 21 days or on a weekly schedule; OR Docetaxel on Day 1, given every 21 days; OR Irinotecan on Days 1 and 8, given every 21 days
Investigator chosen chemotherapy (ICC)	Docetaxel	Paclitaxel on Day 1, given every 21 days or on a weekly schedule; OR Docetaxel on Day 1, given every 21 days; OR Irinotecan on Days 1 and 8, given every 21 days
Investigator chosen chemotherapy (ICC)	Irinotecan	Paclitaxel on Day 1, given every 21 days or on a weekly schedule; OR Docetaxel on Day 1, given every 21 days; OR Irinotecan on Days 1 and 8, given every 21 days

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set	Approximately 2 years and 10 months from date of first randomization	OS is defined as the length of time from the date of randomization until the date of death due to any cause in all randomized participants

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS) in the PDL-1 Positive Analysis Set	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)	OS is defined as the time from the date of randomization until the date of death due to any cause in the PD-L1 positive population, defined as vCPS ≥10%.
Objective Response Rate (ORR) in the ITT Analysis Set	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)	ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;
Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)	ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1;
Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)	PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the PDL-1 Positive Analysis Set
Duration of Response (DOR) in the ITT Analysis Set	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)	DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first
HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set	Baseline to Cycle 6 (21 days per cycle)	Mean change from baseline in EORTC QLQ-C30 Index score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer participants. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes
Number of Participants Experiencing Adverse Events (AEs)	From the first dose date to 30 days after the last dose date; up to approximately 4 years and 11 months	Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs
Progression-free Survival (PFS) in the ITT Analysis Set	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)	PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the ITT analysis set
Duration of Response (DOR) in the PDL-1 Positive Analysis Set.	Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)	DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first
Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C-30) in the ITT Analysis Set	Baseline to Cycle 6 (21 days per cycle)	Mean change from baseline in EORTC QLQ-C30 index score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer participants. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes
HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set	Baseline to Cycle 6 (21 days per cycle)	Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set.	Baseline to Cycle 6 (21 days per cycle)	Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set	Baseline to Cycle 6 (21 days per cycle)	Mean change from baseline in EQ-5D-5L visual acuity score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.
HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set	Baseline to Cycle 6 (21 days per cycle)	Mean change from baseline in EQ-5D-5L visual acuity score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.

Trial Locations

Locations (137)

St. Joseph Heritage Healthcare; 🇺🇸 Fullerton, California, United States

University of Southern California Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Northwestern Medicine Cancer Center Warrenville; 🇺🇸 Warrenville, Illinois, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Toledo Clinic Cancer Center; 🇺🇸 Toledo, Ohio, United States

San Antonio Military Medical Center; 🇺🇸 Fort Sam Houston, Texas, United States

Millennium Oncology; 🇺🇸 Houston, Texas, United States

Imelda Ziekenhuis; 🇧🇪 Antwerp, Belgium

UZ Antwerpen; 🇧🇪 Antwerp, Belgium

Cliniques universitaires Saint-Luc; 🇧🇪 Brussels, Belgium

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