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

NCT ID: NCT03430843

Last Updated: 2024-10-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

512 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-01-26

Study Completion Date

2022-12-28

Brief Summary

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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.

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

NONE

Study Groups

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Tislelizumab

Tislelizumab on Day 1, given every 21 days

Group Type EXPERIMENTAL

Tislelizumab

Intervention Type DRUG

200 mg administered intravenously (IV)

Investigator chosen chemotherapy (ICC)

Paclitaxel 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

Group Type ACTIVE_COMPARATOR

Paclitaxel

Intervention Type DRUG

135-175 mg /m² administered IV , or 80-100 mg/m\^2 administered IV according to local guidelines for standard of care

Docetaxel

Intervention Type DRUG

75 mg/m\^2 administered IV or 70 mg/m\^2 IV in Japan

Irinotecan

Intervention Type DRUG

125 mg/m\^2 administered IV

Interventions

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Tislelizumab

200 mg administered intravenously (IV)

Intervention Type DRUG

Paclitaxel

135-175 mg /m² administered IV , or 80-100 mg/m\^2 administered IV according to local guidelines for standard of care

Intervention Type DRUG

Docetaxel

75 mg/m\^2 administered IV or 70 mg/m\^2 IV in Japan

Intervention Type DRUG

Irinotecan

125 mg/m\^2 administered IV

Intervention Type DRUG

Other Intervention Names

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BGB-A317

Eligibility Criteria

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Inclusion Criteria

1. Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC)
2. Tumor progression during or after first-line treatment for advanced unresectable / metastatic ESCC
3. At least one measurable/evaluable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 prior to randomization

Exclusion Criteria

1. Receipt of 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC
2. History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization
3. 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
4. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
5. Received prior therapies targeting programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1)
6. 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)
7. Active brain or leptomeningeal metastasis.
8. Has active autoimmune disease or history of autoimmune diseases at high risk for relapse
9. 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
10. Known history of Human Immunodeficiency Virus (HIV)
11. Has cardiovascular risk factors
12. Pregnant or breastfeeding woman.
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

Locations

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Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Toledo Clinic Cancer Center

Toledo, Ohio, United States

Site Status

Imelda Ziekenhuis Bonheiden

Bonheiden, , Belgium

Site Status

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Site Status

Uz Antwerpen

Edegem, , Belgium

Site Status

University Hospitals Leuven

Leuven, , Belgium

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

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status

Peking Union Medical College Hospital

Beijing, Beijing Municipality, China

Site Status

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Site Status

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Site Status

The First Affiliated Hospital, Sun Yat Sen University

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

Peking University Shenzhen Hospital

Shenzhen, Guangdong, China

Site Status

Affiliated Hospital of Hebei University

Baoding, Hebei, 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

Huaian Second Peoples Hospital

Huaian, Jiangsu, China

Site Status

Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China

Site Status

Jiangsu Province Hospital

Nanjing, Jiangsu, China

Site Status

Nantong Tumor Hospital Branch South

Nantong, Jiangsu, China

Site Status

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, China

Site Status

Jiangxi Province Cancer Hospital

Nanchang, Jiangxi, China

Site Status

The First Hospital of Jilin University

Changchun, Jilin, China

Site Status

The Second Affiliated Hospital of Xian Jiaotong University

Xi'an, Shaanxi, 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

Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital

Chengdu, Sichuan, China

Site Status

Yunnan Cancer Hospital

Kunming, Yunnan, China

Site Status

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status

Chru de Brest Hospital Morvan

Brest, , France

Site Status

Centre Georges Francois Leclerc

Dijon, , France

Site Status

Chu Besancon Hopital Jean Minjoz

Doubs, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Hopital Prive Jean Mermoz

Lyon, , France

Site Status

Icm Val Daurelle

Montpellier, , France

Site Status

Chu Bordeaux Hopital Haut Leveque

Pessac, , France

Site Status

Chu de Poitiers Site de La Mileterie

Poitiers, , France

Site Status

Ico Site Rene Gauducheau

SaintHerblain, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Charite Universitatsmedizin Berlin

Berlin, , Germany

Site Status

Universitares Krebszentrum Leipzig

Leipzig, , Germany

Site Status

Klinikum Johannes Gutenberg Universitaet Mainz

Mainz, , Germany

Site Status

Ospedale Di Faenza

Faenza, , Italy

Site Status

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst

Meldola, , Italy

Site Status

Azienda Ospedaliero Universitaria San Luigi Gonzaga

Orbassano, , Italy

Site Status

Aou Pisana, Stabilimento Di Santa Chiara

Pisa, , Italy

Site Status

Ao Citta Della Salute E Della Scienza Di Torino Presidio O

Torino, , Italy

Site Status

Akita University Hospital

Akitashi, Akita, Japan

Site Status

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status

Nho Shikoku Cancer Center

Matsuyama, Ehime, Japan

Site Status

Nho Kyushu Cancer Center

Fukuoka, Fukuoka, Japan

Site Status

Kobe City Medical Center General Hospital

Kobe, Hyōgo, Japan

Site Status

St Marianna University School of Medicine Hospital

Yokohama, Kanagawa, Japan

Site Status

Osaka International Cancer Institute

Osakashi, Osaka, Japan

Site Status

Kindai University Hospital

Sayama, Osaka, Japan

Site Status

Osaka University Hospital

Suitashi, Osaka, Japan

Site Status

Osaka Medical and Pharmaceutical University Hospital

Takatsukishi, Osaka, Japan

Site Status

Saitama Cancer Center

Kitaadachigun, Saitama, Japan

Site Status

Shizuoka Cancer Center

Suntogun, Shizuoka, Japan

Site Status

National Cancer Center Hospital

Chuoku, Tokyo, Japan

Site Status

Cancer Institute Hospital of Jfcr

Kotoku, Tokyo, Japan

Site Status

Hiroshima University Hospital

Hiroshima, , Japan

Site Status

Kochi Health Sciences Center

Kochi, , Japan

Site Status

Kyoto University Hospital

Kyoto, , Japan

Site Status

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Gachon University Gil Medical Center

Incheon, Incheon Gwang'yeogsi, South Korea

Site Status

Chonnam National University Hwasun Hospital

HwasunGun, Jeollanam-do, South Korea

Site Status

Asan Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Samsung Medical Center

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Korea University Guro Hospital

Seoul, Seoul Teugbyeolsi, South Korea

Site Status

Hospital Del Mar

Barcelona, , Spain

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 Universitario Ramon Y Cajal

Madrid, , Spain

Site Status

Hospital Universitario de Octubre

Madrid, , Spain

Site Status

Hospital Universitario Hm Madrid Sanchinarro

Madrid, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Chi Mei Hospital Liouying

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital East Campus

Taipei, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , 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

Sarah Cannon Research Institute Uk

London, , United Kingdom

Site Status

St Marys Hospital Imperial College Healthcare Nhs Trust

London, , United Kingdom

Site Status

Mount Vernon Hospital (Mount Vernon Cancer Center)

Northwood, , United Kingdom

Site Status

Royal Marsden Nhs Foundation Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States Belgium China France Germany Italy Japan South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type RESULT
PMID: 35442766 (View on PubMed)

Lu 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.

Reference Type DERIVED
PMID: 40179324 (View on PubMed)

He 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.

Reference Type DERIVED
PMID: 38414510 (View on PubMed)

Hara 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.

Reference Type DERIVED
PMID: 38240916 (View on PubMed)

Kim 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.

Reference Type DERIVED
PMID: 37846080 (View on PubMed)

Van 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.

Reference Type DERIVED
PMID: 35785595 (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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2017-003699-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CTR20171026

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-A317-302

Identifier Type: -

Identifier Source: org_study_id

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