A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
A Randomized, Controlled, Open-label, Global Phase 3 Study Comparing the Efficacy of the Anti-PD-1 Antibody Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Patients With Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma
3 other identifiers
interventional
512
11 countries
104
Brief Summary
The purpose of this study was to evaluate the efficacy and safety of tislelizumab as second line treatment in participants with advanced unresectable/metastatic ESCC that had progressed during or after first line therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2018
Longer than P75 for phase_3
104 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 26, 2018
CompletedFirst Submitted
Initial submission to the registry
January 29, 2018
CompletedFirst Posted
Study publicly available on registry
February 13, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 28, 2022
CompletedResults Posted
Study results publicly available
December 29, 2023
CompletedOctober 26, 2024
October 1, 2024
2.8 years
January 29, 2018
November 10, 2023
October 23, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set
OS is defined as the length of time from the date of randomization until the date of death due to any cause in all randomized participants
Approximately 2 years and 10 months from date of first randomization
Secondary Outcomes (14)
Overall Survival (OS) in the PDL-1 Positive Analysis Set
Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Objective Response Rate (ORR) in the ITT Analysis Set
Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets
Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Progression-free Survival (PFS) in the ITT Analysis Set
Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set
Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- +9 more secondary outcomes
Study Arms (2)
Tislelizumab
EXPERIMENTALTislelizumab on Day 1, given every 21 days
Investigator chosen chemotherapy (ICC)
ACTIVE COMPARATORPaclitaxel on Day 1, given every 21 days or on a weekly schedule; OR Docetaxel on Day 1, given every 21 days; OR Irinotecan on Days 1 and 8, given every 21 days
Interventions
135-175 mg /m² administered IV , or 80-100 mg/m\^2 administered IV according to local guidelines for standard of care
75 mg/m\^2 administered IV or 70 mg/m\^2 IV in Japan
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC)
- Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC
- At least one measurable/evaluable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization
You may not qualify if:
- Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC
- History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization
- Tumor invasion into organs located adjacent to the esophageal disease site (eg, aorta or respiratory tract) at an increased risk of fistula in the study treatment assessed by investigator
- Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
- Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)
- Prior malignancy active within the previous 2 years (exceptions include the tumor under investigation in this trial, and locally recurring cancers that have undergone curative treatment, such as resected basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, cervix or breast)
- Active brain or leptomeningeal metastasis.
- Has active autoimmune disease or history of autoimmune diseases at high risk for relapse
- Known history of, or any evidence of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis diagnosed based on imaging or clinical findings, or uncontrolled systemic diseases, including diabetes, hypertension, acute lung diseases, etc
- Known history of Human Immunodeficiency Virus (HIV)
- Has cardiovascular risk factors
- Pregnant or breastfeeding woman.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BeiGenelead
Study Sites (104)
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Toledo Clinic Cancer Center
Toledo, Ohio, 43623, United States
Imelda Ziekenhuis Bonheiden
Bonheiden, 2820, Belgium
Cliniques Universitaires Saint Luc
Brussels, 1200, Belgium
Uz Antwerpen
Edegem, 2650, Belgium
University Hospitals Leuven
Leuven, 3000, Belgium
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230601, China
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, 100050, China
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730, China
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001, China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350005, China
Fujian Cancer Hospital
Fuzhou, Fujian, 350014, China
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361003, China
The First Affiliated Hospital, Sun Yat Sen University
Guangzhou, Guangdong, 510080, China
The Sixth Affiliated Hospital, Sun Yat Sen University
Guangzhou, Guangdong, 510655, China
Cancer Hospital of Shantou University Medical College
Shantou, Guangdong, 515031, China
Peking University Shenzhen Hospital
Shenzhen, Guangdong, 518036, China
Affiliated Hospital of Hebei University
Baoding, Hebei, 071000, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000, China
The First Affiliated Hospital of Xinxiang Medical University
Xinxiang, Henan, 453100, China
Henan Cancer Hospital
Zhengzhou, Henan, 450000, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Hubei Cancer Hospital
Wuhan, Hubei, 430079, China
Xiangyang Central Hospital
Xiangyang, Hubei, 441021, China
Hunan Cancer Hospital
Changsha, Hunan, 410013, China
The First Peoples Hospital of Changzhou
Changzhou, Jiangsu, 213000, China
Huaian Second Peoples Hospital
Huaian, Jiangsu, 223002, China
Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008, China
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029, China
Nantong Tumor Hospital Branch South
Nantong, Jiangsu, 226000, China
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221000, China
Jiangxi Province Cancer Hospital
Nanchang, Jiangxi, 330029, China
The First Hospital of Jilin University
Changchun, Jilin, 130021, China
The Second Affiliated Hospital of Xian Jiaotong University
Xi'an, Shaanxi, 710004, China
Shandong Cancer Hospital
Jinan, Shandong, 250117, China
Linyi Cancer Hospital
Linyi, Shandong, 276001, China
Weifang Peoples Hospital
Weifang, Shandong, 261000, China
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200000, China
Shanxi Provincial Peoples Hospital
Taiyuan, Shanxi, 030012, China
Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
Chengdu, Sichuan, 610071, China
Yunnan Cancer Hospital
Kunming, Yunnan, 650100, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
Chru de Brest Hospital Morvan
Brest, 29200, France
Centre Georges Francois Leclerc
Dijon, 21079, France
Chu Besancon Hopital Jean Minjoz
Doubs, 25030, France
Centre Oscar Lambret
Lille, 59000, France
Hopital Prive Jean Mermoz
Lyon, 69008, France
Icm Val Daurelle
Montpellier, 34090, France
Chu Bordeaux Hopital Haut Leveque
Pessac, 33600, France
Chu de Poitiers Site de La Mileterie
Poitiers, 86000, France
Ico Site Rene Gauducheau
SaintHerblain, 44805, France
Institut Gustave Roussy
Villejuif, 94805, France
Charite Universitatsmedizin Berlin
Berlin, 13353, Germany
Universitares Krebszentrum Leipzig
Leipzig, 04103, Germany
Klinikum Johannes Gutenberg Universitaet Mainz
Mainz, 55131, Germany
Ospedale Di Faenza
Faenza, 48018, Italy
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
Meldola, 47014, Italy
Azienda Ospedaliero Universitaria San Luigi Gonzaga
Orbassano, 10043, Italy
Aou Pisana, Stabilimento Di Santa Chiara
Pisa, 56126, Italy
Ao Citta Della Salute E Della Scienza Di Torino Presidio O
Torino, 10126, Italy
Akita University Hospital
Akitashi, Akita, 010-8543, Japan
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577, Japan
Nho Shikoku Cancer Center
Matsuyama, Ehime, 791-0280, Japan
Nho Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395, Japan
Kobe City Medical Center General Hospital
Kobe, Hyōgo, 650-0047, Japan
St Marianna University School of Medicine Hospital
Yokohama, Kanagawa, 216-8511, Japan
Osaka International Cancer Institute
Osakashi, Osaka, 541-8567, Japan
Kindai University Hospital
Sayama, Osaka, 589-8511, Japan
Osaka University Hospital
Suitashi, Osaka, 565-0871, Japan
Osaka Medical and Pharmaceutical University Hospital
Takatsukishi, Osaka, 569-8686, Japan
Saitama Cancer Center
Kitaadachigun, Saitama, 362-0806, Japan
Shizuoka Cancer Center
Suntogun, Shizuoka, 411-8777, Japan
National Cancer Center Hospital
Chuoku, Tokyo, 104-0045, Japan
Cancer Institute Hospital of Jfcr
Kotoku, Tokyo, 135-8550, Japan
Hiroshima University Hospital
Hiroshima, 734-8551, Japan
Kochi Health Sciences Center
Kochi, 781-8555, Japan
Kyoto University Hospital
Kyoto, 6068507, Japan
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620, South Korea
Gachon University Gil Medical Center
Incheon, Incheon Gwang'yeogsi, 21565, South Korea
Chonnam National University Hwasun Hospital
HwasunGun, Jeollanam-do, 58128, South Korea
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 05505, South Korea
Samsung Medical Center
Seoul, Seoul Teugbyeolsi, 06351, South Korea
Korea University Guro Hospital
Seoul, Seoul Teugbyeolsi, 08308, South Korea
Hospital Del Mar
Barcelona, 08003, Spain
Hospital Universitario Vall Dhebron
Barcelona, 08035, Spain
Institut Catala Doncologia
Barcelona, 08908, Spain
Hospital Clinic de Barcelona
Barcelona, 8036, Spain
Hospital Universitario Ramon Y Cajal
Madrid, 28034, Spain
Hospital Universitario de Octubre
Madrid, 28041, Spain
Hospital Universitario Hm Madrid Sanchinarro
Madrid, 28050, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
Chi Mei Hospital Liouying
Tainan, 736, Taiwan
National Taiwan University Hospital East Campus
Taipei, 100225, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
The Christie Hospital
Greater Manchester, M20 4BX, United Kingdom
Guys and St Thomas Hospital Nhs Foundation Trust
London, SE1 9RT, United Kingdom
Sarah Cannon Research Institute Uk
London, W1G 6AD, United Kingdom
St Marys Hospital Imperial College Healthcare Nhs Trust
London, W2 1NY, United Kingdom
Mount Vernon Hospital (Mount Vernon Cancer Center)
Northwood, HA6 2RN, United Kingdom
Royal Marsden Nhs Foundation Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Related Publications (7)
Shen L, Kato K, Kim SB, Ajani JA, Zhao K, He Z, Yu X, Shu Y, Luo Q, Wang J, Chen Z, Niu Z, Zhang L, Yi T, Sun JM, Chen J, Yu G, Lin CY, Hara H, Bi Q, Satoh T, Pazo-Cid R, Arkenau HT, Borg C, Lordick F, Li L, Ding N, Tao A, Shi J, Van Cutsem E; RATIONALE-302 Investigators. Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study. J Clin Oncol. 2022 Sep 10;40(26):3065-3076. doi: 10.1200/JCO.21.01926. Epub 2022 Apr 20.
PMID: 35442766RESULTAjani JA, Wang K, Nikolaidis GF, Coaquira Castro J, Augusto Novis de Figueiredo M, Sun JM, Soulanis K, Tasoulas A, Zhan L. Comparative Efficacy and Safety of Tislelizumab in Second-Line Esophageal Squamous Cell Carcinoma: Systematic Literature Review and Simulated Treatment Comparisons. Adv Ther. 2025 Dec 3. doi: 10.1007/s12325-025-03410-5. Online ahead of print.
PMID: 41335329DERIVEDLu Z, Du W, Jiao X, Wang Y, Shi J, Shi Y, Shu Y, Niu Z, Hara H, Wu J, Hsu CH, Van Cutsem E, Brock MV, Zhang Z, Ding N, Zhang Y, Shen Z, Shen L. NOTCH1 Mutation and Survival Analysis of Tislelizumab in Advanced or Metastatic Esophageal Squamous Cell Carcinoma: A Biomarker Analysis From the Randomized, Phase III, RATIONALE-302 Trial. J Clin Oncol. 2025 Jun;43(16):1898-1909. doi: 10.1200/JCO-24-01818. Epub 2025 Apr 3.
PMID: 40179324DERIVEDHe Q, Shi X, Yan J, Wu M, Gu C, Yu X. Circulating tumor DNA serial monitoring of relapse and responses to tislelizumab immunotherapy as second-line monotherapy for metastatic esophageal squamous cell carcinoma: A prospective study. Mol Clin Oncol. 2024 Feb 9;20(4):29. doi: 10.3892/mco.2024.2727. eCollection 2024 Apr.
PMID: 38414510DERIVEDHara H, Satoh T, Kojima T, Tsushima T, Sunakawa Y, Okada M, Ding N, Wu H, Li L, Yu T, Barnes G, Kato K. Second-line tislelizumab versus chemotherapy in Japanese patients with advanced or metastatic esophageal squamous cell carcinoma: subgroup analysis from RATIONALE-302. Esophagus. 2024 Apr;21(2):102-110. doi: 10.1007/s10388-023-01040-w. Epub 2024 Jan 19.
PMID: 38240916DERIVEDKim SB, Van Cutsem E, Ajani J, Shen L, Barnes G, Ding N, Tao A, Xia T, Zhan L, Kato K. Tislelizumab in advanced/metastatic esophageal squamous cell carcinoma: health-related quality of life in Asian patients. Curr Med Res Opin. 2024 Jan;40(1):69-75. doi: 10.1080/03007995.2023.2270894. Epub 2024 Jan 3.
PMID: 37846080DERIVEDVan Cutsem E, Kato K, Ajani J, Shen L, Xia T, Ding N, Zhan L, Barnes G, Kim SB. Tislelizumab versus chemotherapy as second-line treatment of advanced or metastatic esophageal squamous cell carcinoma (RATIONALE 302): impact on health-related quality of life. ESMO Open. 2022 Aug;7(4):100517. doi: 10.1016/j.esmoop.2022.100517. Epub 2022 Jul 1.
PMID: 35785595DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The impact on treatment was considered very limited due to the small number of patients remaining on treatment, the short COVID-19 restriction period (in Asia), and limited restrictions for healthcare visits (in Europe/North America).
Results Point of Contact
- Title
- Study Director
- Organization
- BeiGene
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2018
First Posted
February 13, 2018
Study Start
January 26, 2018
Primary Completion
December 1, 2020
Study Completion
December 28, 2022
Last Updated
October 26, 2024
Results First Posted
December 29, 2023
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will share