Tislelizumab in Combination With Chemotherapy as First-Line Treatment in Adults With Inoperable, Locally Advanced or Metastatic Gastric, or Gastroesophageal Junction Carcinoma
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Clinical Study Comparing the Efficacy and Safety of Tislelizumab (BGB-A317) Plus Platinum and Fluoropyrimidine Versus Placebo Plus Platinum and Fluoropyrimidine as First-Line Treatment in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
4 other identifiers
interventional
997
13 countries
149
Brief Summary
This study was designed to compare the efficacy and safety of tislelizumab plus chemotherapy versus placebo plus chemotherapy as the first treatment (first-line) for adults diagnosed with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2018
Longer than P75 for phase_3
149 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
First Submitted
Initial submission to the registry
November 9, 2018
CompletedStudy Start
First participant enrolled
December 13, 2018
CompletedFirst Posted
Study publicly available on registry
December 17, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 27, 2024
CompletedResults Posted
Study results publicly available
February 14, 2025
CompletedFebruary 14, 2025
January 1, 2025
4.2 years
November 9, 2018
January 24, 2025
January 24, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Overall Survival in PD-L1 Positive Participants
Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.
From randomization up to the primary analysis data cut-off date of 8 October 2021; Median (range) time on follow-up was 11.8 (0.1 - 33.4) months.
Overall Survival in the Intent-to-Treat (ITT) Analysis Set
Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.
From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
Secondary Outcomes (17)
Progression-free Survival (PFS) in PD-L1 Positive Participants
From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
Overall Response Rate (ORR) in PD-L1 Positive Participants
Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
Progression-free Survival (PFS) in the ITT Analysis Set
From randomization up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
Overall Response Rate (ORR) in the ITT Analysis Set
Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
Duration of Response (DOR) in PD-L1 Positive Participants
Response was assessed every 6 weeks for the first 48 weeks and every 9 weeks thereafter; up to the final efficacy analysis data cut-off date of 28 February 2023; Median (range) time on follow-up was 13.2 (0.1 - 50.1) months.
- +12 more secondary outcomes
Study Arms (2)
Tislelizumab + Chemotherapy
EXPERIMENTALParticipants received 200 mg of tislelizumab intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Chemotherapy consisted of 1000 mg/m² capecitabine twice daily on Days 1-14 and 130 mg/m² oxaliplatin on Day 1, or 800 mg/m² 5-fluorouracil (5-FU) on Days 1-5 and 80 mg/m² cisplatin on Day 1 of each 21-day cycle. Thereafter, participants continued treatment with 200 mg tislelizumab, with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Placebo + Chemotherapy
PLACEBO COMPARATORParticipants received placebo intravenously with investigator's choice of chemotherapy once every 3 weeks for up to six treatment cycles. Chemotherapy consisted of 1000 mg/m² capecitabine twice daily on Days 1-14 and 130 mg/m² oxaliplatin on Day 1, or 800 mg/m² 5-FU on Days 1-5 and 80 mg/m² cisplatin on Day 1 of each 21-day cycle. Thereafter, participants continued treatment with placebo with optional maintenance capecitabine (only permitted for participants who initially received capecitabine and oxaliplatin) once every 3 weeks until disease progression or unacceptable toxicity.
Interventions
200 mg intravenously (IV) on Day 1 of each 21-day cycle
80 mg/m² IV on Day 1 of each 21-day cycle
130 mg/m² IV on Day 1 of each 21-day cycle
1000 mg/m² orally twice daily (BD) Days 1 through 14 (14 days total) of each 21-day cycle
800 mg/m²/day IV using continuous infusion on Days 1 to 5 of each 21-day cycle
Eligibility Criteria
You may qualify if:
- Locally advanced unresectable or metastatic gastric cancer (GC) or gastroesophageal junction (GEJ) carcinoma and have histologically confirmed adenocarcinoma
- No previous systemic therapy for locally advanced unresectable or metastatic gastric/GEJ cancer. NOTE: Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed and have no recurrence or disease progression for at least 6 months.
- Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1 within 7 days prior to randomization
- Adequate organ function ≤ 7 days prior to randomization
You may not qualify if:
- Has squamous cell or undifferentiated or other histological type GC
- Active leptomeningeal disease or uncontrolled brain metastasis
- Diagnosed with gastric or GEJ adenocarcinoma with positive HER2
- Prior therapy with an anti-programmed cell death protein-1 (PD-1), anti-programmed cell death protein ligand-1 (PD-L1), anti-programmed cell death protein ligand-2 (PD-L2), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- BeiGenelead
Study Sites (149)
University of California Davis Health System
Sacramento, California, 95817, United States
Southeastern Regional Medical Center
Newnan, Georgia, 30265, United States
Ohio State University Hospital
Columbus, Ohio, 43210, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
Reading Hospital
West Reading, Pennsylvania, 19611, United States
Tennessee Oncology, Pllc Nashville
Nashville, Tennessee, 37203, United States
The First Affiliated Hospital of Bengbu Medical College
Bengbu, Anhui, 233004, China
Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital
Hefei, Anhui, 230088, China
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230601, China
Peking University Third Hospital
Beijing, Beijing Municipality, 100000, China
Beijing Chao Yang Hospital
Beijing, Beijing Municipality, 100020, China
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021, 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
Chinese Pla General Hospital
Beijing, Beijing Municipality, 100853, China
Beijing Luhe Hospital, Capital Medical University
Beijing, Beijing Municipality, 101149, China
Daping Hospital, Third Military Medical University
Chongqing, Chongqing Municipality, 400042, China
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350005, China
Fujian Cancer Hospital
Fuzhou, Fujian, 350014, China
The First Hospital of Lanzhou University
Lanzhou, Gansu, 730000, China
Foshan First Peoples Hospital
Foshan, Guangdong, 528000, China
Sun Yat Sen University Cancer Center
Guangzhou, Guangdong, 510060, China
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, 510080, China
Shenzhen Peoples Hospital
Shenzhen, Guangdong, 518020, China
Affiliated Hospital of Guilin Medical University
Guilin, Guangxi, 541001, China
Hainan General Hospital
Haikou, Hainan, 570206, China
The Fourth Hospital of Hebei Medical University
Shijiazhuang, Hebei, 050011, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000, China
Henan Cancer Hospital
Zhengzhou, Henan, 450000, China
Henan Provincial Peoples Hospital
Zhengzhou, Henan, 450003, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, 430022, China
Hubei Cancer Hospital
Wuhan, Hubei, 430079, China
Xiangya Hospital of Central South University
Changsha, Hunan, 410008, China
Hunan Cancer Hospital
Changsha, Hunan, 410013, China
Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008, China
Nantong Tumor Hospital Branch South
Nantong, Jiangsu, 226000, China
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006, China
The First Hospital of Jilin University
Changchun, Jilin, 130021, China
The First Hospital of China Medical University
Shenyang, Liaoning, 110001, China
The General Hospital of Shenyang Military
Shenyang, Liaoning, 110016, China
Liaoning Cancer Hospital and Institute
Shenyang, Liaoning, 110042, China
Shandong Cancer Hospital
Jinan, Shandong, 250117, China
Linyi Cancer Hospital
Linyi, Shandong, 276001, China
The Affiliated Hospital of Qingdao University Branch South
Qingdao, Shandong, 266000, China
Rui Jin Hospital Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025, China
Affiliated Zhongshan Hospital of Fudan University
Shanghai, Shanghai Municipality, 200032, China
Shanghai General Hospital
Shanghai, Shanghai Municipality, 200080, China
Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200092, China
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052, China
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060, China
Yunnan Cancer Hospital
Kunming, Yunnan, 650100, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003, China
Zhejiang University College of Medicine Second Affiliated Hospital
Hangzhou, Zhejiang, 310009, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016, China
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022, China
Centre Georges Francois Leclerc
Dijon, 21079, France
Chu Besancon Hopital Jean Minjoz
Doubs, 25030, France
Hopital de La Timone
Marseille, 13005, France
Icl Alexis Vautrin
Meurthe Et Moselle, 54519, France
Hopital Nord Franche Comte Site Du Mittan
Montbéliard, 25200, France
Centre Antoine Lacassagne
Nice, 06100, France
Chu Bordeaux Hopital Haut Leveque
Pessac, 33600, France
Azienda Ospedaliera Universitaria Policlinico Santorsola Malpighi
Bologna, 40138, Italy
Fondazione Irccs Istituto Nazionale Dei Tumori
Milan, 20133, Italy
Istituto Nazionale Tumori Fondazione G Pascale
Napoli, 80131, Italy
Iov Istituto Oncologico Veneto Irccs
Padua, 35128, Italy
Ao Ospedali Riuniti Marche Nord
Pesaro, 61122, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126, Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma, 133, Italy
Irccs Ospedale Casa Sollievo Della Sofferenza
San Giovanni Rotondo, 71013, Italy
Aou Senese Policlinico Santa Maria Alle Scotte
Siena, 53100, Italy
Azienda Ospedaliera Citta Della Salute E Della Scienza Di Torino
Torino, 10126, Italy
Azienda Ospedaliera Universitaria Delle Marche
Torrette, 60020, Italy
Chiba Cancer Center
Chiba, Chiba, 260-8717, Japan
Tesshokai Kameda General Hospital
Kamogawashi, Chiba, 296-8602, Japan
Nho Shikoku Cancer Center
Matsuyama, Ehime, 791-0280, Japan
Nho Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395, Japan
Gunma Prefectural Cancer Center
Otashi, Gunma, 373-8550, Japan
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648, Japan
Johas Kansai Rosai Hospital
Amagasakishi, Hyōgo, 660-8511, Japan
Ishikawa Prefectural Central Hospital
Kanazawa, Ishikawa-ken, 920-8530, Japan
Kagawa University Hospital
Kitagun, Kagawa-ken, 761-0793, Japan
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515, Japan
Oita University Hospital
Yufushi, Oita Prefecture, 879-5593, Japan
Kurashiki Central Hospital
Kurashikishi, Okayama-ken, 710-8602, Japan
Okayama University Hospital
Okayama, Okayama-ken, 700-8558, Japan
Izumi City General Hospital
Izumishi, Osaka, 594-0073, Japan
Nho Osaka National Hospital
Osakashi, Osaka, 540-0006, Japan
Osaka University Hospital
Suitashi, Osaka, 565-0871, Japan
Saitama Medical University International Medical Center
Hidakashi, Saitama, 350-1298, Japan
Saitama Cancer Center
Kitaadachigun, Saitama, 362-0806, Japan
Hamamatsu University School of Medicine, University Hospital
Hamamatsushi, Shizuoka, 431-3192, Japan
National Cancer Center Hospital
Chuoku, Tokyo, 104-0045, Japan
Tokyo Metropolitan Tama Medical Center
Fuchushi, Tokyo, 183-8524, Japan
Cancer Institute Hospital of Jfcr
Kotoku, Tokyo, 135-8550, Japan
Center Hospital of the National Center For Global Health and Medicine
Shinjukuku, Tokyo, 162-8655, Japan
Uniwersyteckie Centrum Kliniczne
Gdansk, 80-952, Poland
Centrum Terapii Wspolczesnej Jm Jasnorzewska Sp Komandytowo Akcyjna
Lodz, 90-242, Poland
Przychodnia Med Polonia Sp Z Oo
Poznan, 60-693, Poland
Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
Warsaw, 02-034, Poland
Pan American Oncology Trials, Llc
Rio Piedras, 00935, Puerto Rico
Arkhangelsk Regional Clinical Oncological Dispensary
Arkhangelsk, Arkhangelskaya oblast, 163045, Russia
Rbih Ivanovo Regional Oncological Dispensary
Ivanovo, Ivanovo Oblast, 153040, Russia
Vitamed Llc
Moscow, Moscow, 121309, Russia
Sbhi of Novosibirsk Region Novosibirsk Regional Oncological Dispensary
Novosibirsk, Novosibirsk Oblast, 630108, Russia
Bih of Omsk Region Clinical Oncology Dispensary
Omsk, Omsk Oblast, 644013, Russia
Private Educational Institution of Higher Education Medical University Reaviz
Samara, Samaraskaya Oblast', 443011, Russia
Pavlov First Saint Petersburg State Medical University
SaintPetersburg, Sankt-Peterburg, 197022, Russia
Fsbi Clinical Research and Practical Center For Specialized Medical Care (Oncology)
SanktPetersburg, Sankt-Peterburg, 197758, Russia
State Budgetary Healthcare Institution Volgograd Regional Clinical Oncology Dispensary
Volgograd, Volgograd Oblast, 400138, Russia
Sbih of Yaroslavl Region Regional Clinical Oncological Hospital
Yaroslavl, Yaroslavl Oblast, 150054, Russia
National Cancer Center
Goyang-si, Gyeonggi-do, 10408, South Korea
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620, South Korea
The Catholic University of Korea, St Vincents Hospital
Suwon, Gyeonggi-do, 16247, South Korea
Ajou University Hospital
Suwon, Gyeonggi-do, 16499, South Korea
Kyungpook National University Chilgok Hospital
Daegu, Gyeongsangbukdo, 41404, South Korea
Chonnam National University Hwasun Hospital
HwasunGun, Jeollanam-do, 58128, South Korea
Seoul National University Hospital
Seoul, Seoul Teugbyeolsi, 03080, South Korea
Severance Hospital Yonsei University Health System
Seoul, Seoul Teugbyeolsi, 03722, South Korea
Asan Medical Center
Seoul, Seoul Teugbyeolsi, 05505, South Korea
Chung Ang University Hospital
Seoul, Seoul Teugbyeolsi, 6973, South Korea
Hospital Clinic de Barcelona
Barcelona, 8036, Spain
Hospital de Basurto
Bilbao, 48013, Spain
Hospital General Universitario de Elche
Elche, 3203, Spain
Hospital General Universitario Gregorio Maranon
Madrid, 28007, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Universitario Hm Madrid Sanchinarro
Madrid, 28050, Spain
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, 28222, Spain
Hospital Regional Universitario de Malaga
Málaga, 29010, Spain
Complejo Hospitalario de Navarra
Pamplona, 31008, Spain
Hospital Universitario Virgen Del Rocio
Seville, 41013, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Initia Oncologia, Slp
Valencia, 46010, Spain
Hospital Universitario Miguel Servet
Zaragoza, 50009, Spain
Kaohsiung Medical University Chung Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
National Cheng Kung University Hospital
Tainan, 704, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Acibadem Adana Hospital
Adana, 01130, Turkey (Türkiye)
Dr Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
Ankara, 06620, Turkey (Türkiye)
Nonu Universitesi Tip Fakultesi
Battalgazi, 44280, Turkey (Türkiye)
Dicle University Medical Faculty
Diyarbakır, 21080, Turkey (Türkiye)
Akdeniz University Hospital
Konyaalt, 07070, Turkey (Türkiye)
Iu C, Clinical Research Excellence Application and Research Center
Stanbul, 34098, Turkey (Türkiye)
Namik Kemal University
Tekirdağ, 59100, Turkey (Türkiye)
Karadeniz Tecnical Uni Med Fac
Trabzon, 61080, Turkey (Türkiye)
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Sarah Cannon Research Institute Uk
London, W1G 6AD, United Kingdom
Related Publications (5)
Cruz-Correa M, Oh DY, Kato K, Tabernero J, Bai Y, Shi J, Lee KW, Hirano H, Spigel D, Wyrwicz L, Pazo Cid R, Cubillo Gracian A, Xu Y, Sheng T, Yang S, Xu RH, Moehler M. Tislelizumab + Chemotherapy in Gastric Cancer: Long-Term RATIONALE-305 Randomized Trial Follow-up. Adv Ther. 2025 Nov 18. doi: 10.1007/s12325-025-03415-0. Online ahead of print.
PMID: 41251890DERIVEDCruz-Correa M, Xu RH, Moehler M, Oh DY, Kato K, Spigel D, Arkenau HT, Tabernero J, Zimina AV, Bai Y, Shi J, Lee KW, Hirano H, Wyrwicz L, Cid RP, Xu H, Sheng T, Barnes G. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma: patient-reported outcomes in the RATIONALE-305 study. Curr Med Res Opin. 2025 Jun;41(6):1007-1016. doi: 10.1080/03007995.2025.2501588. Epub 2025 Jun 18.
PMID: 40528576DERIVEDMoehler M, Oh DY, Kato K, Arkenau T, Tabernero J, Lee KW, Rha SY, Hirano H, Spigel D, Yamaguchi K, Wyrwicz L, Disel U, Pazo-Cid RA, Fornaro L, Xu Y, Sheng T, Yang S, Kadva A, Cruz-Correa M, Xu RH. First-Line Tislelizumab Plus Chemotherapy for Advanced Gastric Cancer with Programmed Death-Ligand 1 Expression >/= 1%: A Retrospective Analysis of RATIONALE-305. Adv Ther. 2025 May;42(5):2248-2268. doi: 10.1007/s12325-025-03133-7. Epub 2025 Mar 13.
PMID: 40075025DERIVEDLi W, Wan L, Zhang J. Cost-effectiveness of tislelizumab plus chemotherapy vs chemotherapy as first-line treatment of PD-L1 positive advanced gastric or gastroesophageal junction adenocarcinoma from a Chinese perspective. Expert Rev Gastroenterol Hepatol. 2024 Jun;18(6):293-301. doi: 10.1080/17474124.2024.2373730. Epub 2024 Jun 28.
PMID: 38923910DERIVEDQiu MZ, Oh DY, Kato K, Arkenau T, Tabernero J, Correa MC, Zimina AV, Bai Y, Shi J, Lee KW, Wang J, Poddubskaya E, Pan H, Rha SY, Zhang R, Hirano H, Spigel D, Yamaguchi K, Chao Y, Wyrwicz L, Disel U, Cid RP, Fornaro L, Evesque L, Wang H, Xu Y, Li J, Sheng T, Yang S, Li L, Moehler M, Xu RH; RATIONALE-305 Investigators. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial. BMJ. 2024 May 28;385:e078876. doi: 10.1136/bmj-2023-078876.
PMID: 38806195DERIVED
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- BeiGene
Study Officials
- STUDY DIRECTOR
Jin Wang, MD
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
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2018
First Posted
December 17, 2018
Study Start
December 13, 2018
Primary Completion
February 28, 2023
Study Completion
August 27, 2024
Last Updated
February 14, 2025
Results First Posted
February 14, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share