A Study to Investigate Tislelizumab (BGB-A317) Versus Placebo in Combination With Concurrent Chemoradiotherapy in Participants With Localized Esophageal Squamous Cell Carcinoma

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Tislelizumab (BGB-A317) Versus Placebo in Combination With Concurrent Chemoradiotherapy in Patients With Localized Esophageal Squamous Cell Carcinoma

This is a phase 3, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of tislelizumab (BGB-A317) versus placebo in combination with chemoradiotherapy in participants with localized esophageal squamous cell carcinoma (ESCC).

Study Overview

• Status: Completed
• Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
• Intervention / Treatment: Drug: Paclitaxel; Drug: Cisplatin; Radiation: Radiotherapy; Drug: Tislelizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 370
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400030
      • Chongqing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospitalschool of Clinical Medicine of Guangdong Pharmaceutical University
    • Jieyang, Guangdong, China, 522000
      • Jieyang Peoples Hospital (Jieyang Affiliated Hospital, Sun Yat Sen University )
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Xinxiang, Henan, China, 453100
      • The First Affiliated Hospital of Xinxiang Medical University
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China, 010028
      • Inner Mongolia Autonomous Region Cancer Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Changzhou Tumor(Fourth Peoples)Hospital
    • Lianyungang, Jiangsu, China, 222002
      • The First Peoples Hospital of Lianyungang
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital of Xuzhou Medical University
    • Yangzhou, Jiangsu, China, 225001
      • Northern Jiangsu Peoples Hospital
    • Zhenjiang, Jiangsu, China, 212001
      • Affiliated Hospital of Jiangsu University
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xian Jiaotong University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Fudan University Shanghai Cancer Center
  • Shanxi
    • Changzhi, Shanxi, China, 046000
      • Heping Hospital affiliated to Changzhi Medical College
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610041
      • Sichuan Cancer Hospital and Institute
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Hangzhou Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, Zhejiang University School of Medicine
    • Jinhua, Zhejiang, China, 321000
      • Jinhua Municipal Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Histologically confirmed diagnosis of localized ESCC and suitable for concurrent chemoradiotherapy (cCRT)
• Measurable and/or non-measurable disease defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
• Adequate organ function

Key Exclusion Criteria:

• Indicators of severe malnutrition
• Clinically uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention within 2 weeks prior to randomization
• Known to be intolerable or resistant to treatment with the protocol-specified chemotherapy
• Received prior radiotherapy or therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1), PD-L2 or other immune-oncology therapies
• Active autoimmune diseases or history of autoimmune diseases that may relapse

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab + Chemoradiotherapy; Participants received 200 mg tislelizumab administered intravenously (IV) once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by 200 mg tislelizumab for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first. Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).	Drug: Paclitaxel; Administered as 135 mg/m² IV injection; Drug: Cisplatin; Administered as 25 mg/m² IV injection; Radiation: Radiotherapy; Administered at a total dose of 50.4 Gy in 28 fractions; Drug: Tislelizumab; Administered intravenously (IV); Other Names: BGB-A317; Tevimbra
Placebo Comparator: Placebo + Chemoradiotherapy; Participants received placebo IV once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by placebo for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first. Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).	Drug: Paclitaxel; Administered as 135 mg/m² IV injection; Drug: Cisplatin; Administered as 25 mg/m² IV injection; Radiation: Radiotherapy; Administered at a total dose of 50.4 Gy in 28 fractions; Drug: Placebo; Placebo to match tislelizumab administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	PFS is defined as the time from randomization to the first documented disease progression, as determined by the Blinded Independent Review Committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, and/or unequivocal progression of existing nontarget lesions. or the appearance of one or more new lesions.	From randomization to the prespecified primary analysis data cut-off date of 08 January 2025; maximum time on study was 67 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause. OS was estimated using the Kaplan-Meier method.	From randomization to the prespecified analysis data cut-off date of 08 January 2025; maximum time on study was 67 months.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Oesophageal Cancer Module (OES18) Dysphagia, Reflux, Pain, and Eating Scales	The EORTC-QLQ-OES18 is the specific esophageal symptoms module of the QLQ-C30. QLQ-OES18 is comprised of 18 questions grouped into 4 multi-item subscales: Dysphagia (3 items), Eating (4 items), Reflux (2 items), and Pain (3 items) and 6 single item subscales (saliva swallowing, choking, dry mouth, taste, coughing, and talking). Participants indicate the extent to which they have experienced symptoms on a scale from 1 (Not at all) to 4 (Very much). Scores are calculated and transformed to a scale from 0 to 100; higher scores indicate a higher level of symptomatology or problems.	Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days)
Change From Baseline in EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL), Physical Functioning, and Fatigue Scores	The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life. Lower scores in symptom scales indicate better quality of life.	Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days)
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by BIRC per RECIST v1.1. Tumor assessments were made using computed tomography (CT) scans or using magnetic resonance imaging (MRI). CR: Disappearance of all target lesions and non-target lesions, no new lesions, and normalization of tumor marker level. All lymph nodes must be nonpathological in size (<10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters and/or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.	Tumor assessments occurred every 9 weeks for the first 54 weeks, and every 12 weeks during the next 2 years and every 24 weeks thereafter until radiographic disease progression or death; up to 67 months
Duration of Response (DOR)	DOR is defined as the time from the first occurrence of a documented objective response to the time of relapse, as determined by the BIRC per RECIST v1.1, or death from any cause, whichever occurs first. DOR was estimated using the Kaplan-Meier method.	Up to 67 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment, whether considered related to study treatment or not. A TEAE is an AE that had an onset date or a worsening in severity from baseline on or after the first dose of study treatment and up to 30 days following study treatment discontinuation or initiation of new anticancer therapy, whichever occurred first. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose: Resulted in death; Was life-threatening; Required hospitalization or prolongation of existing hospitalization; Resulted in disability/incapacity; Was a congenital anomaly/birth defect; Was considered a significant medical AE by the investigator based on medical judgement.	From first dose of study drug to 30 days after last dose, maximum time on treatment was 57.5 months

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Weihu Wang, MD, Peking University Cancer Hospital & Institute; Principal Investigator: Zefen Xiao, MD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

General Publications

• Yu R, Wang W, Li T, Li J, Zhao K, Wang W, Liang L, Wu H, Ai T, Huang W, Li L, Yu W, Wei C, Wang Y, Shen W, Xiao Z. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021 Nov;17(31):4081-4089. doi: 10.2217/fon-2021-0632. Epub 2021 Jul 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2019
• Primary Completion (Actual): January 8, 2025
• Study Completion (Actual): March 31, 2025

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Organic Chemicals; Therapeutics; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Taxoids; Cyclodecanes; Diterpenes; Platinum Compounds; Paclitaxel; Cisplatin; Radiotherapy; tislelizumab
• Other Study ID Numbers: BGB-A317-311; CTR20190198 (Registry Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No