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

A Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Efficacy and Safety of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First-Line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma

The purpose of this study is to evaluate the efficacy and safety of tislelizumab as first line treatment in combination with chemotherapy in participants with advanced unresectable/metastatic esophageal squamous cell carcinoma (ESCC).

Study Overview

• Status: Completed
• Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
• Intervention / Treatment: Drug: Cisplatin; Drug: Oxaliplatin; Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Paclitaxel; Biological: Tislelizumab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 649
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
      • Coffs Harbour Base Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincents Hospital Melbourne
• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Brugge, Belgium, 8000
    • Az Sint Jan Brugge
  • Charleroi, Belgium, 6000
    • Grand Hopital de Charleroi Site Notre Dame
  • Gand, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • University Hospitals Leuven
  • Liege, Belgium, 4000
    • CHC MontLegia
• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Hospital
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital aka West Branch of Anhui Province Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer hospital
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100071
      • The Fifth Medical Center of Chinese PLA General Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University
    • Quanzhou, Fujian, China, 362000
      • Quanzhou First Affliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China, 361003
      • The First Affiliated Hospital of Xiamen University
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510405
      • The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital, Sun Yat Sen University
    • Guangzhou, Guangdong, China, 510655
      • Guangdong Province Traditional Chinese Medical Hospitsal
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital, Sun Yat Sen University
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The Tumor Hospital Affiliated to Guangxi Medical University
  • Hainan
    • Haikou, Hainan, China, 570206
      • Hainan General Hospital
  • 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, 450052
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Xiangyang, Hubei, China, 441021
      • Xiangyang Central Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • The First Peoples Hospital of Changzhou
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Nantong, Jiangsu, China, 226000
      • Nantong Tumor Hospital Branch North
    • Wuxi, Jiangsu, China, 214062
      • Affiliated Hospital of Jiangnan University North Campus (Wuxi Fourth Peoples Hospital )
    • Xuzhou, Jiangsu, China, 221000
      • The Affiliated Hospital of Xuzhou Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital and Institute
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
    • Linyi, Shandong, China, 276001
      • Linyi Cancer Hospital
    • Weifang, Shandong, China, 261000
      • Weifang Peoples Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Fudan University Shanghai Cancer Center
  • Shanxi
    • Taiyuan, Shanxi, China, 030012
      • Shanxi Provincial Peoples Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang 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
• Czechia
  • Praha, Czechia, 140 59
    • Fakultni Thomayerova nemocnice
• France
  • Brest, France, 29200
    • Chru de Brest Hopital Cavale Blanche
  • Doubs, France, 25030
    • CHU Besançon Hopital Jean Minjoz
  • LevalloisPerret, France, 92300
    • Hopital Franco Britannique
  • Lille, France, 59000
    • Centre Oscar Lambret
  • Lyon Cedex, France, 69373
    • Centre Leon Berard
  • Paris, France, 75015
    • Hôpital Européen Georges Pompidou
  • Paris Cedex, France, 75012
    • Hopital Saint Antoine Service Dhepato Gastro Enterologie
  • Pessac, France, 33600
    • CHU Bordeaux Hopital Haut Leveque
  • Poitiers, France, 86000
    • Chu de Poitiers Site de La Mileterie
  • SaintHerblain, France, 44805
    • Centre de Lutte Contre Le Cancer Institut de Cancerologie de Louest Rene Gauducheau
• Germany
  • Hamburg, Germany, 20251
    • Universitatsklinikum Hamburg Eppendorf
  • Heilbronn, Germany, 74078
    • Slk Kliniken Heilbronn Gmbh Klinik Fur Radiologie, Minimalinvasive Therapien Und Nuklearmedizin
  • Leipzig, Germany, 04103
    • Universitares Krebszentrum Leipzig
• Italy
  • Meldola, Italy, 47014
    • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione G Pascale
  • Padova, Italy, 35128
    • IOV Istituto Oncologico Veneto IRCCS
  • Torrette, Italy, 60020
    • Azienda Ospedaliera Universitaria Delle Marche
• Japan
  • Hiroshima, Japan, 734-0037
    • Hiroshima University Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Akita
    • Akitashi, Akita, Japan, 010-8543
      • Akita University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Fukuoka
    • FukuokaShi, Fukuoka, Japan, 811-1395
      • Nho Kyushu Cancer Center
    • Fukuokacity, Fukuoka, Japan, 810-8563
      • National Hospital Organization Kyushu Medical Center
  • Hyogo
    • AkashiShi, Hyogo, Japan, 673-0021
      • Hyogo Cancer Center
    • Amagasakishi, Hyogo, Japan, 660-8511
      • JOHAS Kansai Rosai Hospital
  • Kanagawa
    • Yokohamashi, Kanagawa, Japan, 241-8515
      • Kanagawa cancer center
  • Kyoto
    • KyotoShi, Kyoto, Japan, 602-8566
      • University Hospital, Kyoto Prefectural Univ of Medicine
  • Osaka
    • OsakaShi, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
    • Suitashi, Osaka, Japan, 565-0871
      • The University of Osaka Hospital
  • Saitama
    • Kitaadachigun, Saitama, Japan, 362-0806
      • Saitama Cancer Center
  • Tokyo
    • ChuoKu, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Daegu Gwang'yeogsi
    • Dalseogu, Daegu Gwang'yeogsi, Korea, Republic of, 42601
      • Keimyung University Dongsan Hospital
  • Gyeonggi-do
    • BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of, 13496
      • CHA Bundang Medical Center, CHA University
    • BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
  • Incheon Gwang'yeogsi
    • NamdongGu, Incheon Gwang'yeogsi, Korea, Republic of, 21565
      • Gachon University Gil Medical Center
  • Jeollanam-do
    • HwasunGun, Jeollanam-do, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital
  • Seoul Teugbyeolsi
    • DongjakGu, Seoul Teugbyeolsi, Korea, Republic of, 07061
      • Smg Snu Boramae Medical Center
    • GuroGu, Seoul Teugbyeolsi, Korea, Republic of, 08308
      • Korea University Guro Hospital
    • SeochoGu, Seoul Teugbyeolsi, Korea, Republic of, 06591
      • The Catholic University of Korea, Seoul St Marys Hospital
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 135-740
      • Samsung Medical Center Hematology Oncology
    • SongpaGu, Seoul Teugbyeolsi, Korea, Republic of, 05505
      • Asan Medical Center
• Poland
  • Brzozow, Poland, 36-200
    • Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
  • Koszalin, Poland, 75-581
    • Szpital Wojewodzki Im Mikoaja Kopernika W Koszalinie
  • Olsztyn, Poland, 10-228
    • Spzoz Mswia Z Warminsko Mazurskim Centrum Onkologii
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
• Romania
  • ClujNapoca, Romania, 400015
    • Institutul Oncologic Prof Dr Ion Chiricuta Cluj Napoca
  • ClujNapoca, Romania, 400641
    • Medisprof Cancer Center
  • ClujNapoca, Romania, 407280
    • Radiotherapy Center Cluj
  • Craiova, Romania, 200347
    • Sc Centrul de Oncologie Sf Nectarie Srl
• Russian Federation
  • SaintPetersburg, Russian Federation, 197758
    • Fsbi National Medical Research Center For Oncology Na Nn Petrov of the Moh of the Rf
  • Arkhangel'skaya Oblast'
    • Arkhangelsk, Arkhangel'skaya Oblast', Russian Federation, 163045
      • Arkhangelsk Regional Clinical Oncological Dispensary
  • Ivanovskaya Oblast'
    • Ivanovo, Ivanovskaya Oblast', Russian Federation, 153040
      • Rbih Ivanovo Regional Oncological Dispensary
  • Leningradskaya Oblast'
    • Kuzmolovsky, Leningradskaya Oblast', Russian Federation, 188663
      • State Budget Healthcare Institution Leningrad Regional Clinical Oncologic Dispensary
  • Orenburgskaya Oblast'
    • Orenburg, Orenburgskaya Oblast', Russian Federation, 460021
      • Orenburg Regional Clinical Oncology Center
  • Rostovskaya Oblast'
    • RostovonDon, Rostovskaya Oblast', Russian Federation, 344022
      • Rostov State Medical University
  • Sankt-Peterburg
    • SaintPetersburg, Sankt-Peterburg, Russian Federation, 197022
      • Pavlov First Saint Petersburg State Medical University
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall dHebron
  • Barcelona, Spain, 08908
    • Institut Catala Doncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Oviedo, Spain, 33011
    • Hospital Universitario Central de Asturias
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
• Taiwan
  • Chiayi, Taiwan, 61363
    • Chiayi Chang Gung Memorial Hospital
  • Liuying Dist, Taiwan, 73657
    • Chi Mei Hospital Liouying
  • North Dist, Taiwan, 404327
    • China Medical University Hospital
  • Yongkang Dist, Taiwan, 710
    • Chi Mei Medical Center
• United Kingdom
  • Greater Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas Hospital Nhs Foundation Trust
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3220
      • Smilow Cancer Hospital at Yale
  • Texas
    • The Woodlands, Texas, United States, 77380-3476
      • Renovatio Clinical

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Pathologically (histologically) confirmed diagnosis of ESCC
2. Stage IV unresectable ESCC at first diagnosis OR unresectable, locally advanced recurrent or metastatic disease (per American Joint Committee on Cancer 7th Edition), if there is prior neoadjuvant/adjuvant therapy with platinum-based chemotherapy, a treatment-free interval of at least 6 months is required.

Key Exclusion Criteria:

1. Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation
2. Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC
3. Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2
4. Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta)
5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention)
6. Evidence of complete esophageal obstruction not amenable to treatment
7. Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) < 83.5 per investigator's choice
8. Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator.
9. Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is ≥ 500 IU/mL or participants with active hepatitis C virus (HCV)

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: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab + Chemotherapy; Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons. Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).	Drug: Cisplatin; Cisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan.; Drug: Oxaliplatin; Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.; Drug: Fluorouracil (5-FU); Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.; Drug: Capecitabine; Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle; Drug: Paclitaxel; Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.; Biological: Tislelizumab; Tislelizumab 200 mg administered by intravenous infusion every 3 weeks.; Other Names: BGB-A317; TEVIMBRA
Active Comparator: Placebo + Chemotherapy; Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons. Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).	Drug: Cisplatin; Cisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan.; Drug: Oxaliplatin; Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.; Drug: Fluorouracil (5-FU); Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.; Drug: Capecitabine; Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle; Drug: Paclitaxel; Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.; Drug: Placebo; Placebo to match tislelizumab administered by intravenous infusion every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority.	From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-free survival is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Progressive disease is defined as 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, or unequivocal progression of existing nontarget lesions, or the appearance of 1 or more new lesions. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.	From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Objective Response Rate (ORR)	ORR is defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1. Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the neck, chest, and abdomen. CR: Disappearance of all target and nontarget lesions with no new lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm. PR: Disappearance of all target lesions with persistence of 1 or more nontarget lesion(s), no new lesions, and/or maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis (data cutoff date of 28 February 2022).	Response was assessed every 6 weeks for the first 48 weeks, then every 9 weeks thereafter; up to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Overall Survival (OS) in Participants With a PD-L1 Score ≥ 10%	OS is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.	From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Duration of Response (DOR)	DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.	From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Oesophageal Cancer 18 Question Module (QLQ-OES18) Dysphagia, Eating, Reflux, Pain, and Index Scores	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 (trouble swallowing saliva, 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 as the average of the items that contribute to the scale, then transformed to a scale from 0 to 100. The OES18 index score is calculated as the average of the 4 multi-item subscales and 6 single-item subscales. Higher scores indicate a higher level of symptomatology or problems.	Baseline, Cycle 6 (Week 15)
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) and Physical Functioning Scales	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 to a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life.	Baseline, Cycle 6 (Week 15)
Change From Baseline in EORTC QLQ-C30 Fatigue Scale	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 to a 0 to 100 scale via linear transformation. The fatigue symptom scale includes 3 items and ranges from 0 to 100, where higher scores indicate a higher level of symptoms.	Baseline, Cycle 6 (Week 15)
Change From Baseline in European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (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.	Baseline, Cycle 6 (Week 15)
Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	An 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 study drugs, whether related to study drugs or not. An SAE is any untoward medical occurrence that, at any dose met any of the following criteria: 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 up to 30 days after last dose; maximum time on treatment was 63.5 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	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	Approximately 40 months from date of the first participant randomization
Objective Response Rate (ORR)	ORR is defined as the proportion of participants whose best overall response (BOR) is complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1	Approximately 40 months from date of the first participant randomization
Overall survival (OS) in the PD-L1 score ≥ 10% subgroup	OS is defined as the time from the date of randomization until the date of death due to any cause	Approximately 40 months from date of the first participant randomization
Duration of Response (DOR)	DOR is defined as the time from the first determination of an objective response until the first documentation of progression assessed by the investigator per RECIST v1.1 or death, whichever comes first	Approximately 40 months from date of the first participant randomization
Health-Related Quality of Life (HRQoL) assessment of the participant's overall health status using European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30)		Approximately 40 months from date of the first participant randomization
Health-Related Quality of Life (HRQoL) assessment of the participant's overall health status using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer specific module (EORTC QLQ-OES18)		Approximately 40 months from date of the first participant randomization
Health-Related Quality of Life (HRQoL) assessment of the participant's overall health status using the generic health state instrument European Quality of Life-5 Dimensions (EuroQol 5D EQ-5D-5L)		Approximately 40 months from date of the first participant randomization
Number of participants experiencing Adverse Events (AEs)		Approximately 40 months from date of the first participant randomization

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Study Director: Study Director, BeiGene

Publications and helpful links

General Publications

• Xu J, Kato K, Raymond E, Hubner RA, Shu Y, Pan Y, Park SR, Ping L, Jiang Y, Zhang J, Wu X, Yao Y, Shen L, Kojima T, Gotovkin E, Ishihara R, Wyrwicz L, Van Cutsem E, Jimenez-Fonseca P, Lin CY, Wang L, Shi J, Li L, Yoon HH. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2023 May;24(5):483-495. doi: 10.1016/S1470-2045(23)00108-0. Epub 2023 Apr 17.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2018
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): August 22, 2024

Study Registration Dates

• First Submitted: December 18, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

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; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma; Carcinoma, Squamous Cell; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Capecitabine; Oxaliplatin; Tislelizumab; Fluorouracil; Paclitaxel
• Other Study ID Numbers: BGB-A317-306; 2018-000587-28 (EudraCT Number); CTR20181013 (Other Identifier: ChinaDrugTrials); JapicCTI-194741 (Registry Identifier: Japic)

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