TriangleNCT03783442 · CITED IN SOURCE DOCUMENTS
A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2025-07-29
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).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Overall Survival (OS)
Progression-Free Survival (PFS)
Objective Response Rate (ORR)
Overall Survival (OS) in Participants With a PD-L1 Score ≥ 10%
Duration of Response (DOR)
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
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
Change From Baseline in EORTC QLQ-C30 Fatigue Scale
Change From Baseline in European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS)
Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Key Inclusion Criteria: 1. Pathologically (histologically) confirmed diagnosis of ESCC 2. Stage IV unresectable ESCC at first diagnosis OR unresectable, locally advanced recurrent or metastatic disease (per American Joint Committee on Cancer 7th Edition), if there is prior neoadjuvant/adjuvant therapy with platinum-based chemotherapy, a treatment-free interval of at least 6 months is required. Key Exclusion Criteria: 1. Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation 2. Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC 3. Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2 4. Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta) 5. Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (clinically significant recurrence requiring an additional intervention within 2 weeks of intervention) 6. Evidence of complete esophageal obstruction not amenable to treatment 7. Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) \< 83.5 per investigator's choice 8. Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator. 9. Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers whose HBV DNA is ≥ 500 IU/mL or participants with active hepatitis C virus (HCV) NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- 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).
- intervention Names
- Drug: Cisplatin
- Drug: Oxaliplatin
- Drug: Fluorouracil (5-FU)
- Drug: Capecitabine
- Drug: Paclitaxel
- Biological: Tislelizumab
- label
- Tislelizumab + Chemotherapy
- type
- EXPERIMENTAL
- description
- 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).
- intervention Names
- Drug: Cisplatin
- Drug: Oxaliplatin
- Drug: Fluorouracil (5-FU)
- Drug: Capecitabine
- Drug: Paclitaxel
- Drug: Placebo
- label
- Placebo + Chemotherapy
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Placebo + Chemotherapy
- Tislelizumab + Chemotherapy
- description
- Cisplatin 60-80 mg/m² administered by intravenous infusion every 3 weeks. Cisplatin was used as the platinum agent in China, Taiwan, and Japan.
- name
- Cisplatin
- type
- DRUG
- arm Group Labels
- Placebo + Chemotherapy
- Tislelizumab + Chemotherapy
- description
- Oxaliplatin 130 mg/m² administered by intravenous infusion every 3 weeks.
- name
- Oxaliplatin
- type
- DRUG
- arm Group Labels
- Placebo + Chemotherapy
- Tislelizumab + Chemotherapy
- description
- Fluorouracil 750-800 mg/m² administered by intravenous infusion on Days 1-5 of each treatment cycle.
- name
- Fluorouracil (5-FU)
- type
- DRUG
- arm Group Labels
- Placebo + Chemotherapy
- Tislelizumab + Chemotherapy
- description
- Capecitabine 1000 mg/m² administered orally twice daily on Days 1-14 of each treatment cycle
- name
- Capecitabine
- type
- DRUG
- arm Group Labels
- Placebo + Chemotherapy
- Tislelizumab + Chemotherapy
- description
- Paclitaxel 175 mg/m² administered by intravenous infusion every 3 weeks.
- name
- Paclitaxel
- type
- DRUG
- arm Group Labels
- Tislelizumab + Chemotherapy
- description
- Tislelizumab 200 mg administered by intravenous infusion every 3 weeks.
- name
- Tislelizumab
- other Names
- BGB-A317
- TEVIMBRA
- type
- BIOLOGICAL
- arm Group Labels
- Placebo + Chemotherapy
- description
- Placebo to match tislelizumab administered by intravenous infusion every 3 weeks.
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- DOUBLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 649
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- 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.
- secondary Outcomes
- description
- 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.
- measure
- 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.
- description
- 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).
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- Change From Baseline in EORTC QLQ-C30 Fatigue Scale
- time Frame
- Baseline, Cycle 6 (Week 15)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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.
Full study description
- brief 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).
Source references
- references
- citation
- 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.
- pmid
- 37080222
- type
- RESULT
- citation
- Moehler 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.
- pmid
- 40373876
- type
- DERIVED
- citation
- Xu J, Kato K, Hubner R, Park SR, Kojima T, Ishihara R, Wyrwicz L, Van Cutsem E, Jimenez-Fonseca P, Wu H, Wang L, Yan S, Shi J, Kadva A, Yoon HH. First-Line Tislelizumab Plus Chemotherapy for Esophageal Squamous Cell Carcinoma with Programmed Death-Ligand 1 Expression >/= 1%: A Retrospective Analysis of RATIONALE-306. Adv Ther. 2025 May;42(5):2269-2284. doi: 10.1007/s12325-025-03115-9. Epub 2025 Mar 13.
- pmid
- 40075024
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice