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

NCT ID: NCT03783442

Last Updated: 2025-07-29

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

649 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-11

Study Completion Date

2024-08-22

Brief Summary

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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).

Detailed Description

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Conditions

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Esophageal Squamous Cell Carcinoma (ESCC)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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).

Group Type EXPERIMENTAL

Cisplatin

Intervention Type DRUG

Cisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan.

Oxaliplatin

Intervention Type DRUG

Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.

Fluorouracil (5-FU)

Intervention Type DRUG

Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.

Capecitabine

Intervention Type DRUG

Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle

Paclitaxel

Intervention Type DRUG

Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.

Tislelizumab

Intervention Type BIOLOGICAL

Tislelizumab 200 mg administered by intravenous infusion every 3 weeks.

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).

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Cisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan.

Oxaliplatin

Intervention Type DRUG

Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.

Fluorouracil (5-FU)

Intervention Type DRUG

Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.

Capecitabine

Intervention Type DRUG

Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle

Paclitaxel

Intervention Type DRUG

Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.

Placebo

Intervention Type DRUG

Placebo to match tislelizumab administered by intravenous infusion every 3 weeks.

Interventions

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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.

Intervention Type DRUG

Oxaliplatin

Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.

Intervention Type DRUG

Fluorouracil (5-FU)

Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.

Intervention Type DRUG

Capecitabine

Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle

Intervention Type DRUG

Paclitaxel

Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.

Intervention Type DRUG

Tislelizumab

Tislelizumab 200 mg administered by intravenous infusion every 3 weeks.

Intervention Type BIOLOGICAL

Placebo

Placebo to match tislelizumab administered by intravenous infusion every 3 weeks.

Intervention Type DRUG

Other Intervention Names

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BGB-A317 TEVIMBRA

Eligibility Criteria

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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.

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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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BeiGene

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Study Director

Role: STUDY_DIRECTOR

BeiGene

Locations

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Smilow Cancer Hospital At Yale

New Haven, Connecticut, United States

Site Status

Renovatio Clinical

The Woodlands, Texas, United States

Site Status

Coffs Harbour Base Hospital

Coffs Harbour, New South Wales, Australia

Site Status

St Vincents Hospital Melbourne

Fitzroy, Victoria, Australia

Site Status

Institut Jules Bordet

Anderlecht, , Belgium

Site Status

Az Sint Jan Brugge

Bruges, , Belgium

Site Status

Grand Hopital de Charleroi Site Notre Dame

Charleroi, , Belgium

Site Status

UZ GENT

Ghent, , Belgium

Site Status

University Hospitals Leuven

Leuven, , Belgium

Site Status

Chc Montlegia

Liège, , Belgium

Site Status

Anhui Provincial Hospital

Hefei, Anhui, China

Site Status

Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital

Hefei, Anhui, China

Site Status

The Second Hospital of Anhui Medical University

Hefei, Anhui, China

Site Status

Beijing Friendship Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status

The Fifth Medical Center of Chinese Pla General Hospital

Beijing, Beijing Municipality, China

Site Status

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status

Quanzhou First Affliated Hospital of Fujian Medical University

Quanzhou, Fujian, China

Site Status

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Site Status

Zhongshan Hospital Xiamen University

Xiamen, Fujian, China

Site Status

The First Affiliated Hospital, Sun Yat Sen University

Guangzhou, Guangdong, China

Site Status

The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine

Guangzhou, Guangdong, China

Site Status

Guangdong Province Traditional Chinese Medical Hospitsal

Guangzhou, Guangdong, China

Site Status

The Sixth Affiliated Hospital, Sun Yat Sen University

Guangzhou, Guangdong, China

Site Status

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, China

Site Status

The Tumor Hospital Affiliated to Guangxi Medical University

Nanning, Guangxi, China

Site Status

Hainan General Hospital

Haikou, Hainan, China

Site Status

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status

The First Affiliated Hospital of Xinxiang Medical University

Xinxiang, Henan, China

Site Status

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status

Hubei Cancer Hospital

Wuhan, Hubei, China

Site Status

Xiangyang Central Hospital

Xiangyang, Hubei, China

Site Status

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status

The First Peoples Hospital of Changzhou

Changzhou, Jiangsu, China

Site Status

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Site Status

Nantong Tumor Hospital Branch North

Nantong, Jiangsu, China

Site Status

Affiliated Hospital of Jiangnan University North Campus (Wuxi Fourth Peoples Hospital )

Wuxi, Jiangsu, China

Site Status

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status

Liaoning Cancer Hospital and Institute

Shenyang, Liaoning, China

Site Status

Shandong Cancer Hospital

Jinan, Shandong, China

Site Status

Linyi Cancer Hospital

Linyi, Shandong, China

Site Status

Weifang Peoples Hospital

Weifang, Shandong, China

Site Status

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status

Shanxi Provincial Peoples Hospital

Taiyuan, Shanxi, China

Site Status

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Site Status

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status

Fakultni Thomayerova Nemocnice

Prague, , Czechia

Site Status

Chru de Brest Hopital Cavale Blanche

Brest, , France

Site Status

Chu Besancon Hopital Jean Minjoz

Doubs, , France

Site Status

Hopital Franco Britannique

LevalloisPerret, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Hopital Saint Antoine Service Dhepato Gastro Enterologie

Paris, , France

Site Status

Hopital Europeen Georges Pompidou

Paris, , France

Site Status

Chu Bordeaux Hopital Haut Leveque

Pessac, , France

Site Status

Chu de Poitiers Site de La Mileterie

Poitiers, , France

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Centre de Lutte Contre Le Cancer Institut de Cancerologie de Louest Rene Gauducheau

SaintHerblain, , France

Site Status

Universitatsklinikum Hamburg Eppendorf

Hamburg, , Germany

Site Status

Slk Kliniken Heilbronn Gmbh Klinik Fur Radiologie, Minimalinvasive Therapien Und Nuklearmedizin

Heilbronn, , Germany

Site Status

Universitares Krebszentrum Leipzig

Leipzig, , Germany

Site Status

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst

Meldola, , Italy

Site Status

Istituto Europeo Di Oncologia

Milan, , Italy

Site Status

Istituto Nazionale Tumori Fondazione G Pascale

Napoli, , Italy

Site Status

Iov Istituto Oncologico Veneto Irccs

Padua, , Italy

Site Status

Azienda Ospedaliera Universitaria Delle Marche

Torrette, , Italy

Site Status

Akita University Hospital

Akitashi, Akita, Japan

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

Nho Kyushu Cancer Center

Fukuoka, Fukuoka, Japan

Site Status

National Hospital Organization Kyushu Medical Center

Fukuokacity, Fukuoka, Japan

Site Status

Hyogo Cancer Center

AkashiShi, Hyōgo, Japan

Site Status

Johas Kansai Rosai Hospital

Amagasakishi, Hyōgo, Japan

Site Status

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Site Status

University Hospital, Kyoto Prefectural Univ of Medicine

KyotoShi, Kyoto, Japan

Site Status

Osaka International Cancer Institute

OsakaShi, Osaka, Japan

Site Status

The University of Osaka Hospital

Suitashi, Osaka, Japan

Site Status

Saitama Cancer Center

Kitaadachigun, Saitama, Japan

Site Status

National Cancer Center Hospital

ChuoKu, Tokyo, Japan

Site Status

Hiroshima University Hospital

Hiroshima, , Japan

Site Status

Kumamoto University Hospital

Kumamoto, , Japan

Site Status

Niigata Cancer Center Hospital

Niigata, , Japan

Site Status

Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny

Brzozów, , Poland

Site Status

Szpital Wojewodzki Im Mikoaja Kopernika W Koszalinie

Koszalin, , Poland

Site Status

Spzoz Mswia Z Warminsko Mazurskim Centrum Onkologii

Olsztyn, , Poland

Site Status

Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy

Warsaw, , Poland

Site Status

Institutul Oncologic Prof Dr Ion Chiricuta Cluj Napoca

ClujNapoca, , Romania

Site Status

Medisprof Cancer Center

ClujNapoca, , Romania

Site Status

Radiotherapy Center Cluj

ClujNapoca, , Romania

Site Status

Sc Centrul de Oncologie Sf Nectarie Srl

Craiova, , Romania

Site Status

Arkhangelsk Regional Clinical Oncological Dispensary

Arkhangelsk, Arkhangelskaya oblast, Russia

Site Status

Rbih Ivanovo Regional Oncological Dispensary

Ivanovo, Ivanovo Oblast, Russia

Site Status

State Budget Healthcare Institution Leningrad Regional Clinical Oncologic Dispensary

Kuzmolovsky, Leningradskaya Oblast', Russia

Site Status

Orenburg Regional Clinical Oncology Center

Orenburg, Orenburg Oblast, Russia

Site Status

Rostov State Medical University

RostovonDon, Rostov Oblast, Russia

Site Status

Pavlov First Saint Petersburg State Medical University

SaintPetersburg, Sankt-Peterburg, Russia

Site Status

Fsbi National Medical Research Center For Oncology Na Nn Petrov of the Moh of the Rf

SaintPetersburg, , Russia

Site Status

Keimyung University Dongsan Hospital

Dalseogu, Daegu Gwang'yeogsi, South Korea

Site Status

Cha Bundang Medical Center, Cha University

BundangGu SeongnamSi, Gyeonggi-do, South Korea

Site Status

Seoul National University Bundang Hospital

BundangGu SeongnamSi, Gyeonggi-do, South Korea

Site Status

Gachon University Gil Medical Center

NamdongGu, Incheon Gwang'yeogsi, South Korea

Site Status

Chonnam National University Hwasun Hospital

HwasunGun, Jeollanam-do, South Korea

Site Status

Smg Snu Boramae Medical Center

DongjakGu, Seoul Teugbyeolsi, South Korea

Site Status

Korea University Guro Hospital

GuroGu, Seoul Teugbyeolsi, South Korea

Site Status

The Catholic University of Korea, Seoul St Marys Hospital

SeochoGu, Seoul Teugbyeolsi, South Korea

Site Status

Samsung Medical Center Hematology Oncology

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Asan Medical Center

SongpaGu, Seoul Teugbyeolsi, South Korea

Site Status

Hospital Universitario Vall Dhebron

Barcelona, , Spain

Site Status

Institut Catala Doncologia

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Hospital Universitario Central de Asturias

Oviedo, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Chiayi Chang Gung Memorial Hospital

Chiayi City, , Taiwan

Site Status

Chi Mei Hospital Liouying

Liuying Dist, , Taiwan

Site Status

China Medical University Hospital

North Dist, , Taiwan

Site Status

Chi Mei Medical Center

Yongkang Dist, , Taiwan

Site Status

The Christie Hospital

Greater Manchester, , United Kingdom

Site Status

Guys and St Thomas Hospital Nhs Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium China Czechia France Germany Italy Japan Poland Romania Russia South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type RESULT
PMID: 37080222 (View on PubMed)

Xu J, Kato K, Hubner R, Park SR, Kojima T, Ishihara R, Wyrwicz L, Van Cutsem E, Jimenez-Fonseca P, Wu H, Wang L, Yan S, Shi J, Kadva A, Yoon HH. First-Line Tislelizumab Plus Chemotherapy for Esophageal Squamous Cell Carcinoma with Programmed Death-Ligand 1 Expression >/= 1%: A Retrospective Analysis of RATIONALE-306. Adv Ther. 2025 May;42(5):2269-2284. doi: 10.1007/s12325-025-03115-9. Epub 2025 Mar 13.

Reference Type DERIVED
PMID: 40075024 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-000587-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTR20181013

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-194741

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-A317-306

Identifier Type: -

Identifier Source: org_study_id

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