Esophageal Squamous Cell Carcinoma (ESCC)Phase 3NCT03783442
A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
A Phase 3 study testing Cisplatin, Oxaliplatin and Fluorouracil (5-FU) in people with Esophageal Squamous Cell Carcinoma (ESCC), run by BeiGene at 124 sites in 16 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma (ESCC)
- What is being tested?
- Cisplatin, Oxaliplatin and Fluorouracil (5-FU)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 649 participants
- Where
- 124 sitesin 16 countries
- Study dates
- 11 Dec 2018to 22 Aug 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically (histologically) confirmed diagnosis of ESCC
- 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.
Who cannot join
- Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation
- Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC
- Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2
- Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta)
- 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)
- Evidence of complete esophageal obstruction not amenable to treatment
Show all 10Show fewer
- Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) < 83.5 per investigator's choice
- Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator.
- 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.
Trial locations and contacts
124 sites in 16 countries.
124 sites in 16 countries
China42 sites
Beijing Friendship Hospital, Capital Medical University
Beijing, Beijing Municipality, 100050
The Fifth Medical Center of Chinese Pla General Hospital
Beijing, Beijing Municipality, 100071
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Hunan Cancer Hospital
Changsha, Hunan, 410013
The First Peoples Hospital of Changzhou
Changzhou, Jiangsu, 213000
The First Affiliated Hospital of Fujian Medical University
Fuzhou, Fujian, 350005
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
The First Affiliated Hospital, Sun Yat Sen University
Guangzhou, Guangdong, 510080
The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine
Guangzhou, Guangdong, 510405
Guangdong Province Traditional Chinese Medical Hospitsal
Guangzhou, Guangdong, 510655
The Sixth Affiliated Hospital, Sun Yat Sen University
Guangzhou, Guangdong, 510655
Hainan General Hospital
Haikou, Hainan, 570206
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310003
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310016
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, 310022
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000
Anhui Provincial Hospital
Hefei, Anhui, 230000
Anhui Provincial Cancer Hospital Aka West Branch of Anhui Province Hospital
Hefei, Anhui, 230088
The Second Hospital of Anhui Medical University
Hefei, Anhui, 230601
Shandong Cancer Hospital
Jinan, Shandong, 250117
Linyi Cancer Hospital
Linyi, Shandong, 276001
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Jiangsu Province Hospital
Nanjing, Jiangsu, 210029
The Tumor Hospital Affiliated to Guangxi Medical University
Nanning, Guangxi, 530021
Nantong Tumor Hospital Branch North
Nantong, Jiangsu, 226000
Quanzhou First Affliated Hospital of Fujian Medical University
Quanzhou, Fujian, 362000
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200000
Cancer Hospital of Shantou University Medical College
Shantou, Guangdong, 515031
Liaoning Cancer Hospital and Institute
Shenyang, Liaoning, 110042
Shanxi Provincial Peoples Hospital
Taiyuan, Shanxi, 030012
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060
Weifang Peoples Hospital
Weifang, Shandong, 261000
Hubei Cancer Hospital
Wuhan, Hubei, 430079
Affiliated Hospital of Jiangnan University North Campus (Wuxi Fourth Peoples Hospital )
Wuxi, Jiangsu, 214062
The First Affiliated Hospital of Xiamen University
Xiamen, Fujian, 361003
Zhongshan Hospital Xiamen University
Xiamen, Fujian, 361004
Xiangyang Central Hospital
Xiangyang, Hubei, 441021
The First Affiliated Hospital of Xinxiang Medical University
Xinxiang, Henan, 453100
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221000
Henan Cancer Hospital
Zhengzhou, Henan, 450000
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052
Japan15 sites
Hyogo Cancer Center
AkashiShi, Hyōgo, 673-0021
Akita University Hospital
Akitashi, Akita, 010-8543
Johas Kansai Rosai Hospital
Amagasakishi, Hyōgo, 660-8511
National Cancer Center Hospital
ChuoKu, Tokyo, 104-0045
Nho Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
National Hospital Organization Kyushu Medical Center
Fukuokacity, Fukuoka, 810-8563
Hiroshima University Hospital
Hiroshima, 734-0037
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Saitama Cancer Center
Kitaadachigun, Saitama, 362-0806
Kumamoto University Hospital
Kumamoto, 860-8556
University Hospital, Kyoto Prefectural Univ of Medicine
KyotoShi, Kyoto, 602-8566
Niigata Cancer Center Hospital
Niigata, 951-8566
Osaka International Cancer Institute
OsakaShi, Osaka, 541-8567
The University of Osaka Hospital
Suitashi, Osaka, 565-0871
Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515
France10 sites
Chru de Brest Hopital Cavale Blanche
Brest, 29200
Chu Besancon Hopital Jean Minjoz
Doubs, 25030
Hopital Franco Britannique
LevalloisPerret, 92300
Centre Oscar Lambret
Lille, 59000
Centre Leon Berard
Lyon, 69373
Hopital Saint Antoine Service Dhepato Gastro Enterologie
Paris, 75012
Hopital Europeen Georges Pompidou
Paris, 75015
Chu Bordeaux Hopital Haut Leveque
Pessac, 33600
Chu de Poitiers Site de La Mileterie
Poitiers, 86000
Centre de Lutte Contre Le Cancer Institut de Cancerologie de Louest Rene Gauducheau
SaintHerblain, 44805
South Korea10 sites
Cha Bundang Medical Center, Cha University
BundangGu SeongnamSi, Gyeonggi-do, 13496
Seoul National University Bundang Hospital
BundangGu SeongnamSi, Gyeonggi-do, 13620
Keimyung University Dongsan Hospital
Dalseogu, Daegu Gwang'yeogsi, 42601
Smg Snu Boramae Medical Center
DongjakGu, Seoul Teugbyeolsi, 07061
Korea University Guro Hospital
GuroGu, Seoul Teugbyeolsi, 08308
Chonnam National University Hwasun Hospital
HwasunGun, Jeollanam-do, 58128
Gachon University Gil Medical Center
NamdongGu, Incheon Gwang'yeogsi, 21565
The Catholic University of Korea, Seoul St Marys Hospital
SeochoGu, Seoul Teugbyeolsi, 06591
Samsung Medical Center Hematology Oncology
Seoul, Seoul Teugbyeolsi, 135-740
Asan Medical Center
SongpaGu, Seoul Teugbyeolsi, 05505
Russia7 sites
Arkhangelsk Regional Clinical Oncological Dispensary
Arkhangelsk, Arkhangelskaya oblast, 163045
Rbih Ivanovo Regional Oncological Dispensary
Ivanovo, Ivanovo Oblast, 153040
State Budget Healthcare Institution Leningrad Regional Clinical Oncologic Dispensary
Kuzmolovsky, Leningradskaya Oblast', 188663
Orenburg Regional Clinical Oncology Center
Orenburg, Orenburg Oblast, 460021
Rostov State Medical University
RostovonDon, Rostov Oblast, 344022
Pavlov First Saint Petersburg State Medical University
SaintPetersburg, Sankt-Peterburg, 197022
Fsbi National Medical Research Center For Oncology Na Nn Petrov of the Moh of the Rf
SaintPetersburg, 197758
Spain7 sites
Hospital Universitario Vall Dhebron
Barcelona, 08035
Institut Catala Doncologia
Barcelona, 08908
Hospital Clinic de Barcelona
Barcelona, 8036
Hospital General Universitario Gregorio Maranon
Madrid, 28007
Hospital Regional Universitario de Malaga
Málaga, 29010
Hospital Universitario Central de Asturias
Oviedo, 33011
Hospital Universitario Miguel Servet
Zaragoza, 50009
Belgium6 sites
Institut Jules Bordet
Anderlecht, 1070
Az Sint Jan Brugge
Bruges, 8000
Grand Hopital de Charleroi Site Notre Dame
Charleroi, 6000
UZ GENT
Ghent, 9000
University Hospitals Leuven
Leuven, 3000
Chc Montlegia
Liège, 4000
Italy5 sites
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori Irst
Meldola, 47014
Istituto Europeo Di Oncologia
Milan, 20141
Istituto Nazionale Tumori Fondazione G Pascale
Naples, 80131
Iov Istituto Oncologico Veneto Irccs
Padova, 35128
Azienda Ospedaliera Universitaria Delle Marche
Torrette, 60020
Poland4 sites
Szpital Specjalist W Brzozowie,Podkarpacki Osrodek Onkologiczny
Brzozów, 36-200
Szpital Wojewodzki Im Mikoaja Kopernika W Koszalinie
Koszalin, 75-581
Spzoz Mswia Z Warminsko Mazurskim Centrum Onkologii
Olsztyn, 10-228
Narodowy Instytut Onkologii Im Marii Skodowskiej Curie Pastwowy Instytut Badawczy
Warsaw, 02-781
Romania4 sites
Institutul Oncologic Prof Dr Ion Chiricuta Cluj Napoca
ClujNapoca, 400015
Medisprof Cancer Center
ClujNapoca, 400641
Radiotherapy Center Cluj
ClujNapoca, 407280
Sc Centrul de Oncologie Sf Nectarie Srl
Craiova, 200347
Taiwan4 sites
Chiayi Chang Gung Memorial Hospital
Chiayi City, 61363
Chi Mei Hospital Liouying
Liuying Dist, 73657
China Medical University Hospital
North Dist, 404327
Chi Mei Medical Center
Yongkang Dist, 710
Germany3 sites
Universitatsklinikum Hamburg Eppendorf
Hamburg, 20251
Slk Kliniken Heilbronn Gmbh Klinik Fur Radiologie, Minimalinvasive Therapien Und Nuklearmedizin
Heilbronn, 74078
Universitares Krebszentrum Leipzig
Leipzig, 04103
United States2 sites
Smilow Cancer Hospital At Yale
New Haven, Connecticut, 06510-3220
Renovatio Clinical
The Woodlands, Texas, 77380-3476
Australia2 sites
Coffs Harbour Base Hospital
Coffs Harbour, New South Wales, 2450
St Vincents Hospital Melbourne
Fitzroy, Victoria, 3065
United Kingdom2 sites
The Christie Hospital
Greater Manchester, M20 4BX
Guys and St Thomas Hospital Nhs Foundation Trust
London, SE1 9RT
About this study
Official title: 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).
- Being tested
- Cisplatin, Oxaliplatin, Fluorouracil (5-FU), Capecitabine, Paclitaxel
- Medical subject headings
- Esophageal Squamous Cell Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Cisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan.
OxaliplatinDrug
Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.
Fluorouracil (5-FU)Drug
Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.
CapecitabineDrug
Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle
PaclitaxelDrug
Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.
TislelizumabBiological
Also called BGB-A317, TEVIMBRA
Tislelizumab 200 mg administered by intravenous infusion every 3 weeks.
PlaceboDrug
Placebo to match tislelizumab administered by intravenous infusion every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Tislelizumab + Chemotherapy | Experimental | 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). Receives: Drug: Cisplatin; Drug: Oxaliplatin; Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Paclitaxel; Biological: Tislelizumab |
| Placebo + Chemotherapy | Active comparator | 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). Receives: Drug: Cisplatin; Drug: Oxaliplatin; Drug: Fluorouracil (5-FU); Drug: Capecitabine; Drug: Paclitaxel; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS)
Overall survival is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.
Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority.
Measured: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Secondary outcomes (9)
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
Progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, and an absolute increase of at least 5 mm, or unequivocal progression of existing nontarget lesions, or the appearance of 1 or more new lesions.
Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.
Measured: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Objective Response Rate (ORR)
ORR is defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1. Tumor assessments included computed tomography (CT) scans or magnetic resonance imaging (MRI), with preference for CT, of the neck, chest, and abdomen.
CR: Disappearance of all target and nontarget lesions with no new lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm.
PR: Disappearance of all target lesions with persistence of 1 or more nontarget lesion(s), no new lesions, and/or maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis (data cutoff date of 28 February 2022).
Measured: Response was assessed every 6 weeks for the first 48 weeks, then every 9 weeks thereafter; up to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Overall Survival (OS) in Participants With a PD-L1 Score ≥ 10%
OS is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.
Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.
Measured: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
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 occurred first. Median DOR was estimated using the Kaplan-Meier method.
Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority. Testing for all secondary efficacy endpoints was conducted at the time of the primary analysis.
Measured: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Oesophageal Cancer 18 Question Module (QLQ-OES18) Dysphagia, Eating, Reflux, Pain, and Index Scores
The EORTC-QLQ-OES18 is the specific esophageal symptoms module of the QLQ-C30. QLQ-OES18 is comprised of 18 questions grouped into 4 multi-item subscales: Dysphagia (3 items), Eating (4 items), Reflux (2 items), and Pain (3 items) and 6 single item subscales (trouble swallowing saliva, choking, dry mouth, taste, coughing, and talking). Participants indicate the extent to which they have experienced symptoms on a scale from 1 (Not at all) to 4 (Very much). Scores are calculated as the average of the items that contribute to the scale, then transformed to a scale from 0 to 100. The OES18 index score is calculated as the average of the 4 multi-item subscales and 6 single-item subscales. Higher scores indicate a higher level of symptomatology or problems.
Measured: Baseline, Cycle 6 (Week 15)
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) and Physical Functioning Scales
The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed to a 0 to 100 scale via linear transformation. Higher scores in GHS and functional scales indicate better quality of life.
Measured: Baseline, Cycle 6 (Week 15)
Change From Baseline in EORTC QLQ-C30 Fatigue Scale
The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1 = Not at all (best) and 4 = Very Much (worst) and 2 global health quality of life (QOL) questions answered on a 7-point scale where 1 = Very poor and 7 = Excellent. Raw scores are transformed to a 0 to 100 scale via linear transformation. The fatigue symptom scale includes 3 items and ranges from 0 to 100, where higher scores indicate a higher level of symptoms.
Measured: Baseline, Cycle 6 (Week 15)
Change From Baseline in European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS)
The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes.
Measured: Baseline, Cycle 6 (Week 15)
Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drugs, whether related to study drugs or not.
An SAE is any untoward medical occurrence that, at any dose met any of the following criteria:
- Resulted in death
- Was life-threatening
- Required hospitalization or prolongation of existing hospitalization
- Resulted in disability/incapacity
- Was a congenital anomaly/birth defect
- Was considered a significant medical AE by the Investigator based on medical judgement.
Measured: From first dose of study drug up to 30 days after last dose; maximum time on treatment was 63.5 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2018
- Study start11 Dec 2018
- Primary completion28 Feb 2022
- Study completion22 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Esophageal Squamous Cell Carcinoma (ESCC)Studies of the same condition, open and under way.
- More trials run by BeiGeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 649 participants (actual)
Sponsor and investigators
- Lead sponsor
- BeiGene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, BeiGene
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03783442
- Sponsor's protocol ID
- BGB-A317-306
- Other IDs
- 2018-000587-28, CTR20181013, JapicCTI-194741, 2018
- Status last verified
- Jul 2025
- First submitted
- 18 Dec 2018
- Last updated
- 29 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
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.
PubMed 37080222Yoon HH, Kato K, Raymond E, Hubner R, Shu Y, Pan Y, Park SR, Kojima T, Lin CY, Wyrwicz L, Tougeron D, Ishihara R, Wang K, Peng Y, Xu J. First-line tislelizumab plus chemotherapy versus placebo plus chemotherapy in unresectable advanced/metastatic esophageal squamous cell carcinoma: minimum 3-year survival follow-up of a randomized phase 3 trial (RATIONALE-306). Nat Commun. 2026 Sep 3;17(1):10499. doi: 10.1038/s41467-026-77327-0.
PubMed 42834033Moehler M, Yoon HH, Wagner DC, Yang S, Shi J, Zhang Y, Hu H, La Placa C, Peng Y, Du W, McCampbell A, Xu W, Shen Z, Xu H, Huang R, Kato K. Concordance Between the PD-L1 Tumor Area Positivity Score and Combined Positive Score for Gastric or Esophageal Cancers Treated With Tislelizumab. Mod Pathol. 2025 Sep;38(9):100793. doi: 10.1016/j.modpat.2025.100793. Epub 2025 May 13.
PubMed 40373876Xu 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.
PubMed 40075024
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03783442
- Acronym / sponsor ID
- BGB-A317-306
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 649 participants (actual)
- Lead sponsor
- BeiGeneIndustry (pharma, biotech, devices)
- Study start
- 11 Dec 2018 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 22 Aug 2024 (actual)
- First posted
- 21 Dec 2018 (actual)
- Results
- Posted 7 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tislelizumab + Chemotherapy | Experimental | Drug: Cisplatin, Drug: Oxaliplatin, Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Paclitaxel, Biological: TislelizumabParticipants 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). |
| Placebo + Chemotherapy | Active comparator | Drug: Cisplatin, Drug: Oxaliplatin, Drug: Fluorouracil (5-FU), Drug: Capecitabine, Drug: Paclitaxel, Drug: PlaceboParticipants 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Pathologically (histologically) confirmed diagnosis of ESCC
- 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 (10 listed)
- Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation
- Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC
- Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2
- Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CisplatinCisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan. | Drug | Placebo + Chemotherapy, Tislelizumab + Chemotherapy |
| OxaliplatinOxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks. | Drug | Placebo + Chemotherapy, Tislelizumab + Chemotherapy |
| Fluorouracil (5-FU)Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle. | Drug | Placebo + Chemotherapy, Tislelizumab + Chemotherapy |
| CapecitabineCapecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle | Drug | Placebo + Chemotherapy, Tislelizumab + Chemotherapy |
| PaclitaxelPaclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks. | Drug | Placebo + Chemotherapy, Tislelizumab + Chemotherapy |
| TislelizumabAlso: BGB-A317, TEVIMBRATislelizumab 200 mg administered by intravenous infusion every 3 weeks. | Biological | Tislelizumab + Chemotherapy |
| PlaceboPlacebo to match tislelizumab administered by intravenous infusion every 3 weeks. | Drug | Placebo + Chemotherapy |
Primary outcome
Overall Survival (OS)
Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Overall survival is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority.
9 secondary outcomes
Progression-Free Survival (PFS)
Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Objective Response Rate (ORR)
Time frame: Response was assessed every 6 weeks for the first 48 weeks, then every 9 weeks thereafter; up to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Overall Survival (OS) in Participants With a PD-L1 Score ≥ 10%
Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Duration of Response (DOR)
Time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Oesophageal Cancer 18 Question Module (QLQ-OES18) Dysphagia, Eating, Reflux, Pain, and Index Scores
Time frame: Baseline, Cycle 6 (Week 15)
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) and Physical Functioning Scales
Time frame: Baseline, Cycle 6 (Week 15)
Change From Baseline in EORTC QLQ-C30 Fatigue Scale
Time frame: Baseline, Cycle 6 (Week 15)
Change From Baseline in European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS)
Time frame: Baseline, Cycle 6 (Week 15)
Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug up to 30 days after last dose; maximum time on treatment was 63.5 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37080222Xu 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.
- Derived from this study: PubMed 42834033Yoon HH, Kato K, Raymond E, Hubner R, Shu Y, Pan Y, Park SR, Kojima T, Lin CY, Wyrwicz L, Tougeron D, Ishihara R, Wang K, Peng Y, Xu J. First-line tislelizumab plus chemotherapy versus placebo plus chemotherapy in unresectable advanced/metastatic esophageal squamous cell carcinoma: minimum 3-year survival follow-up of a randomized phase 3 trial (RATIONALE-306). Nat Commun. 2026 Sep 3;17(1):10499. doi: 10.1038/s41467-026-77327-0.
- Derived from this study: PubMed 40373876Moehler M, Yoon HH, Wagner DC, Yang S, Shi J, Zhang Y, Hu H, La Placa C, Peng Y, Du W, McCampbell A, Xu W, Shen Z, Xu H, Huang R, Kato K. Concordance Between the PD-L1 Tumor Area Positivity Score and Combined Positive Score for Gastric or Esophageal Cancers Treated With Tislelizumab. Mod Pathol. 2025 Sep;38(9):100793. doi: 10.1016/j.modpat.2025.100793. Epub 2025 May 13.
- Derived from this study: PubMed 40075024Xu 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.
- Individual participant dataSharing planned: Yes. BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved. BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations. Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
BeiGene
124 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cisplatin, Oxaliplatin and Fluorouracil (5-FU) in people with Esophageal Squamous Cell Carcinoma (ESCC), run by BeiGene at 124 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 124 sites in China, Japan, France, South Korea, Russia and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03783442, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.