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: Active, not recruiting
• Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
• Intervention / Treatment: Drug: Paclitaxel; Drug: Capecitabine; Drug: Cisplatin; Drug: Oxaliplatin; Drug: Tislelizumab; Drug: Placebo; Drug: Fluorouracil (5-FU)

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

Contacts and Locations

Study Locations

• Australia
  • Pacific Highway
    • Coffs Harbour, Pacific Highway, Australia, 2450
      • Coffs Harbour Hospital
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • Townsville Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 6008
      • Ashford Cancer Centre Research
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's hospital
    • Wendouree, Victoria, Australia, 3355
      • Ballarat Oncology & Haematology Services
• Belgium
  • Liège, Belgium, 4000
    • CHC Mont Legia
  • Liège, Belgium, 4000
    • CHU Liège Sart Tilman
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Antwerp University Hospital
  • Brussels Capital Region
    • Anderlecht, Brussels Capital Region, Belgium, 1070
      • Institut Jules Bordet - Oncologie Médicale
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Grand Hôpital de Charleroi - Site Notre-Dame
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent - Radiologie
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • UZ Leuven - Campus Gasthuisberg
  • West-Vlaanderen
    • Brugge, West-Vlaanderen, Belgium, 8000
      • AZ Sint-Jan Brugge - Oostende AV - Campus Sint-Jan - Oncology
• China
  • Hefei, China, 230001
    • Anhui Provincial Hospital - Oncology
  • Xiamen, China, 361005
    • The First Affiliated Hospital of Xiamen University - Oncology
  • Anhui
    • Hefei, Anhui, China, 230601
      • Anhui Medical University - The Second Hospital
    • Hefei, Anhui, China, 230601
      • The Second Affiliated Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230088
      • Anhui Provincial Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100071
      • The Fifth Medical Center of Chinese PLA General Hospital
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital - Oncology
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital - Oncology
    • Beijing, Beijing, China, 100089
      • Chinese PLA General Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Provincial Cancer Hospital - Oncology
    • Fuzhou, Fujian, China, 35005
      • The First Affiliated Hospital of Fujian Medical University
    • Xiamen, Fujian, China, 361004
      • Zhongshan Hospital Xiamen University
  • Guangdong
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510120
      • Guangdong Province Traditional Chinese Medical Hospital
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
  • Guangxi
    • Nanning, Guangxi, China
      • Cancer Hospital of Guangxi Medical University
  • Hainan
    • Haikou, Hainan, China
      • Hainan General Hospital - Oncology
  • Heilongjiang
    • Haerbin, Heilongjiang, China, 150081
      • Affiliated Tumor Hospital of Harbin Medical University
  • Henan
    • Henan, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University - Oncology
    • Xinxiang, Henan, China, 453100
      • The First Affiliated Hospital of Xinxiang Medical University
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital - Oncology
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital - Oncology
    • Xiangyang, Hubei, China, 441021
      • Xiangyang Central Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital - GCP Office
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • The First People's Hospital of Changzhou - Oncology
    • Nanjing, Jiangsu, China, 210029
      • Jiangsu Province Hospital
    • Nantong, Jiangsu, China
      • Nantong Cancer Hospital
    • Wuxi, Jiangsu, China, 214062
      • Affiliated Hospital of Jiangnan University
    • Xuzhou, Jiangsu, China
      • The Affiliated Hospital of Xuzhou Medical University - Radiology
    • Yangzhou, Jiangsu, China, 225001
      • Northern Jiangsu People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
  • Liaoning
    • Shenyang, Liaoning, China, 110017
      • Liaoning Cancer Hospital & Institute - Medical Oncology - Oncology
  • Quanzhou
    • Quanzhou, Quanzhou, China
      • Quanzhou First Hospital - Radiotherapy/Nuclear Medicine
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital and Institute, Shandong First Medical University
    • Linyi, Shandong, China, 276001
      • Linyi Cancer Hospital
    • Weifang, Shandong, China
      • Weifang People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Center
  • Shanxi
    • Taiyuan, Shanxi, China
      • Shanxi Provincial People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University
• Czechia
  • Olomouc, Czechia, 779 00
    • Fakultni Nemocnice Olomouc
  • Praha 4, Czechia, 140 59
    • Thomayerova nemocnice
  • Praha 8, Czechia, 180 81
    • Nemocnice Na Bulovce
• France
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou - Digestive Oncology
  • Paris, France, 75074
    • Groupe Hospitalier Paris Saint Joseph - Oncologie
  • Bretagne
    • Brest Cedex, Bretagne, France, 29609
      • Hôpital Morvan - CHRU de Brest - cancérologie et d'hématologie
  • Doubs
    • Besançon Cedex, Doubs, France, 25030
      • CHRU de Besançon- Hopital Jean Minjoz
  • Gironde
    • Pessac Cedex, Gironde, France, 33608
      • CHU Bordeaux Hôpital Du Haut-Lévêque
  • Hauts-de-Seine
    • Levallois-Perret, Hauts-de-Seine, France, 92300
      • Institut Hospitalier Franco-Britannique (IHFB) - Levallois-Perret - 4 Rue Kleber
  • Loire-Atlantique
    • Saint-Herblain, Loire-Atlantique, France, 44805
      • ICO
  • Nord
    • Lille, Nord, France, 59000
      • Center Oscar Lambret - Alliance Member
  • Paris
    • Paris Cedex 12, Paris, France, 75571
      • Hopital Saint-Antoine / Service d'Hepato-Gastro-Enterologie
  • Rhône
    • Lyon, Rhône, France, 69008
      • Centre Leon Berard
  • Vienne
    • Poitiers, Vienne, France, 86000
      • Centre Hospitalier Universitaire de Poitiers
• Germany
  • Hamburg, Germany, 20251
    • University Hospital Hamburg- Eppendorf
  • Baden-Württemberg
    • Heilbronn, Baden-Württemberg, Germany, 74078
      • SLK Kliniken Heilbronn GmbH - Klinik für Radiologie, Minimalinvasive Therapien und Nuklearmedizin
    • Tuebingen, Baden-Württemberg, Germany, 72076
      • University Hospital Tuebingen
  • Nordrhein-Westfalen
    • Minden, Nordrhein-Westfalen, Germany, 32429
      • Johannes Wesling Klinikum Minden
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55101
      • Universitätsmedizin Mainz
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • University Hospital of Leipzig
• Italy
  • Ancona, Italy, 60126
    • Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc - Oncologia Medica
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Milano, Italy, 20141
    • Ieo, Irccs
  • Napoli, Italy, 80131
    • Fondazione Pascale, IRCCS, Istituto Nazionale dei Tumori
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto IOV-IRCCS
  • Pisa, Italy, 56126
    • SO S.Chiara, AOU Pisana - Oncologia 2
  • Ancona
    • Torino, Ancona, Italy, 60126
      • Ospedale Umberto I, AOU Ospedali Riuniti Umberto I - GM.Lanc - Oncologia Medica
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori', IRCCS - Laboratorio
• Japan
  • Akashi, Japan, 673-8558
    • Hyogo Cancer Center
  • Akita-shi, Japan, 010-8543
    • Akita University Hospital - Pediatrics
  • Amagasaki, Japan, 660-8511
    • Kansai Rosai Hospital - Gastroenterological Surgery
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital - Gastrointestinal Surgery
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute - Clinical Oncology
  • Saitama, Japan, 362-0806
    • Saitama Cancer Center - Gastroenterology
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East - Gastrointestinal Oncology
  • Hukuoka
    • Fukuoka, Hukuoka, Japan, 810-8563
      • Kyushu Medical Center - Gastroenterological Surgery
    • Fukuoka, Hukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center - GI and Medical Oncology
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital - Medical Oncology
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital - Oncology
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center - Gastroenterological surgery
  • Kyoto
    • Kamigyō-ku, Kyoto, Japan, 602-8566
      • University Hospital, Kyoto Prefectural Univ of Medicine - Gastroenterology
  • Osaka
    • Ikoma, Osaka, Japan, 630-0293
      • Kindai University Nara Hospital
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital - Medical Oncology
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital - Gastrointestinal Oncology
• Korea, Republic of
  • Daegu, Korea, Republic of, 42601
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - Oncology
  • Gyeonggido
    • Seongnam-si, Gyeonggido, Korea, Republic of, 13496
      • CHA Bundang Medical Center, CHA University - Oncology
  • Gyeonggido [Kyonggi-do]
    • Seongnam-si, Gyeonggido [Kyonggi-do], Korea, Republic of, 13620
      • Seoul National University Bundang Hospital - Hematology/Oncology
  • Incheon Gwang'yeogsi [Inch'n-K
    • Incheon, Incheon Gwang'yeogsi [Inch'n-K, Korea, Republic of, 21565
      • Gachon University Gil Medical Center - Oncology
  • Jeonranamdo [Chollanam-do]
    • Hwasun, Jeonranamdo [Chollanam-do], Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital - Hematology and Oncology Clinic
  • Seoul Teugbyeolsi [Seoul-T'ukp
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, Korea, Republic of, 06351
      • Samsung Medical Center - Hematology-Oncology
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, Korea, Republic of, 07061
      • SMG-SNU Boramae Medical Center - Oncology
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukp, Korea, Republic of, 08308
      • Korea University Guro Hospital - Hematology-Oncology
  • Seoul Teugbyeolsi [Seoul-T'ukp]
    • Seoul, Seoul Teugbyeolsi [Seoul-T'ukp], Korea, Republic of, 6591
      • The Catholic University of Korea, Seoul St. Mary's Hospital
• Poland
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 02-034
      • Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
  • Podkarpackie
    • Brzozow, Podkarpackie, Poland, 36-200
      • Szpital Specjalist. w Brzozowie,Podkarpacki Ośrodek Onkologi
  • Pomorskie
    • Koszalin, Pomorskie, Poland, 75-581
      • Szpital Wojewodzki w Koszalinie
  • Warminsko-mazurskie
    • Olsztyn, Warminsko-mazurskie, Poland, 10-228
      • SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 60-848
      • Clinical Research Center Sp. z o.o., Medic-R Sp. K.
• Romania
  • Bucuresti, Romania, 022328
    • Institutul Clinic Fundeni
  • Bucuresti, Romania, 030171
    • Spitalul Clinic Coltea
  • Cluj-Napoca, Romania, 400641
    • Medisprof
  • Iaşi, Romania, 700106
    • Centrul de Oncologie Euroclinic
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Institutul Oncologic "Prof.Dr.I.Chiricuta" Cluj Napoca
    • Floreşti, Cluj, Romania, 407280
      • Radiotherapy Center Cluj
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • Centrul de Oncologie Sf. Nectarie
• Russian Federation
  • Ivanovo, Russian Federation, 153015
    • Ivanovo Regional Oncology Dispensary
  • Saint Petersburg, Russian Federation, 197758
    • Petrov Research Institute of Oncology
  • Arkhangel'skaya Oblast'
    • Arkhangelsk, Arkhangel'skaya Oblast', Russian Federation, 163045
      • Arkhangelsk Regional Clinical Oncological Dispensary
  • Leningradskaya Oblast
    • Kuz'molovskiy, Leningradskaya Oblast, Russian Federation, 188663
      • Leningrad Regional Oncology Dispensary
  • Orenburgskaya Oblast
    • Orenburg, Orenburgskaya Oblast, Russian Federation, 460021
      • Orenburg Regional Clinical Oncology Center
  • Rostovskaya Oblast
    • Rostov-Na-Donu, Rostovskaya Oblast, Russian Federation, 344037
      • Rostov Research Institute of Oncology (RRIO)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 194291
      • The First Saint-Petersburg State Medical University named after Academician I.P. Pavlov
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 198255
      • City Oncology Dispensary
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Murcia, Spain, 30120
    • H.U.V.Arrixaca
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias
  • Barcelona
    • L'Hospitalet De Llobregat, Barcelona, Spain, 08907
      • Institut Catalá d´Oncología (I.C.O.)
  • Madrid
    • Sanchinarro, Madrid, Spain, 28050
      • Hospital Madrid Norte Sanchinarro
• Taiwan
  • Kaohsiung, Taiwan, 813
    • Kaohsiung Veterans General Hospital - Thoracic Surgery
  • Kaohsiung, Taiwan, 833
    • Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology
  • Taichung, Taiwan, 40447
    • China Medical University Hospital - Oncology - Taichung
  • Tainan, Taiwan, 71004
    • Chi Mei Medical Center - YongKang - Chi Mei Medical Center
  • Tainan, Taiwan, 73657
    • Chi Mei Hospital, Liouying - Department of Oncology
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust - Oak Road Treatment Centr
  • City Of London
    • London, City Of London, United Kingdom, SE1 9RT
      • Guys and St Thomas' Hospital
    • London, City Of London, United Kingdom, SM2 5PT
      • Royal Marsden NHS Foundation Trust Sutton
    • London, City Of London, United Kingdom, SW3 6JJ
      • The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital
  • England
    • Northwood, England, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre
  • Kent
    • Maidstone, Kent, United Kingdom, ME16 9QQ
      • Maidstone and Tunbridge Wells NHS Trust - Kent Oncology Centre
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0YN
      • Beatson West of Scotland Cancer Centre - Oncology
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3220
      • Smilow Cancer Hospital at Yale-New Haven - Neurology
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212-4756
      • Allegheny General Hospital (AGH)
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina Hollings Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center of San Antonio
    • The Woodlands, Texas, United States, 77389
      • 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; Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days; Chemotherapy Doublet A: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m^2 on Days 1 to 5 of each cycle Q3W;; Chemotherapy Doublet B: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m^2 on Days 1 to 14 of each cycle, twice a day; or; Chemotherapy Doublet C: cisplatin 60-80 mg/m^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines	Drug: Paclitaxel; Administered IV; Drug: Capecitabine; Administered orally; Drug: Cisplatin; Administered IV; Drug: Oxaliplatin; Administered IV; Drug: Tislelizumab; Administered IV; Other Names: BGB-A317; Drug: Fluorouracil (5-FU); Administered IV
Active Comparator: Placebo + Chemotherapy; Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days; Chemotherapy Doublet A: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m^2 on Days 1 to 5 of each cycle Q3W;; Chemotherapy Doublet B: cisplatin 60-80 mg/m^2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines	Drug: Paclitaxel; Administered IV; Drug: Capecitabine; Administered orally; Drug: Cisplatin; Administered IV; Drug: Oxaliplatin; Administered IV; Drug: Placebo; Placebo to match Tislelizumab; Drug: Fluorouracil (5-FU); Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization until the date of death due to any cause	Up to approximately 3 years and 2 months (as of primary analysis data cut-off date of 28FEB2022)

Secondary 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
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
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
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

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. Erratum In: Lancet Oncol. 2024 Mar;25(3):e102.

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2018
• Primary Completion (Actual): February 28, 2022
• Study Completion (Estimated): June 30, 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): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Paclitaxel; Fluorouracil; Capecitabine; Oxaliplatin; Tislelizumab
• Other Study ID Numbers: BGB-A317-306; 2018-000587-28 (EudraCT Number); CTR20181013 (Other Identifier: Center for drug evaluation, CFDA); JapicCTI-194741 (Registry Identifier: Japic)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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