TriangleNCT03430843 · CITED IN SOURCE DOCUMENTS
A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second 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
- 2024-10-26
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.
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) in the Intent-to-Treat (ITT) Analysis Set
Overall Survival (OS) in the PDL-1 Positive Analysis Set
Objective Response Rate (ORR) in the ITT Analysis Set
Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets
Progression-free Survival (PFS) in the ITT Analysis Set
Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set
Duration of Response (DOR) in the ITT Analysis Set
Duration of Response (DOR) in the PDL-1 Positive Analysis Set.
Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C-30) in the ITT Analysis Set
HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set
HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set
HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set.
HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set
HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set
Number of Participants Experiencing Adverse Events (AEs)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Key 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 Key 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. 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
- Tislelizumab on Day 1, given every 21 days
- intervention Names
- Drug: Tislelizumab
- label
- Tislelizumab
- type
- EXPERIMENTAL
- description
- 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
- intervention Names
- Drug: Paclitaxel
- Drug: Docetaxel
- Drug: Irinotecan
- label
- Investigator chosen chemotherapy (ICC)
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Tislelizumab
- description
- 200 mg administered intravenously (IV)
- name
- Tislelizumab
- other Names
- BGB-A317
- type
- DRUG
- arm Group Labels
- Investigator chosen chemotherapy (ICC)
- description
- 135-175 mg /m² administered IV , or 80-100 mg/m\^2 administered IV according to local guidelines for standard of care
- name
- Paclitaxel
- type
- DRUG
- arm Group Labels
- Investigator chosen chemotherapy (ICC)
- description
- 75 mg/m\^2 administered IV or 70 mg/m\^2 IV in Japan
- name
- Docetaxel
- type
- DRUG
- arm Group Labels
- Investigator chosen chemotherapy (ICC)
- description
- 125 mg/m\^2 administered IV
- name
- Irinotecan
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 512
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- OS is defined as the length of time from the date of randomization until the date of death due to any cause in all randomized participants
- measure
- Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set
- time Frame
- Approximately 2 years and 10 months from date of first randomization
- secondary Outcomes
- description
- OS is defined as the time from the date of randomization until the date of death due to any cause in the PD-L1 positive population, defined as vCPS ≥10%.
- measure
- Overall Survival (OS) in the PDL-1 Positive Analysis Set
- time Frame
- Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- description
- ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1;
- measure
- Objective Response Rate (ORR) in the ITT Analysis Set
- time Frame
- Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- description
- ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1;
- measure
- Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets
- time Frame
- Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- description
- PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the ITT analysis set
- measure
- Progression-free Survival (PFS) in the ITT Analysis Set
- time Frame
- Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- description
- PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the PDL-1 Positive Analysis Set
- measure
- Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set
- time Frame
- Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- description
- DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first
- measure
- Duration of Response (DOR) in the ITT Analysis Set
- time Frame
- Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- description
- DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first
- measure
- Duration of Response (DOR) in the PDL-1 Positive Analysis Set.
- time Frame
- Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
- description
- Mean change from baseline in EORTC QLQ-C30 index score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer participants. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes
- measure
- Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C-30) in the ITT Analysis Set
- time Frame
- Baseline to Cycle 6 (21 days per cycle)
- description
- Mean change from baseline in EORTC QLQ-C30 Index score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer participants. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes
- measure
- HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set
- time Frame
- Baseline to Cycle 6 (21 days per cycle)
- description
- Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
- measure
- HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set
- time Frame
- Baseline to Cycle 6 (21 days per cycle)
- description
- Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes.
- measure
- HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set.
- time Frame
- Baseline to Cycle 6 (21 days per cycle)
- description
- Mean change from baseline in EQ-5D-5L visual acuity score (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.
- measure
- HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set
- time Frame
- Baseline to Cycle 6 (21 days per cycle)
Full study description
- brief Summary
- The purpose of this study was to evaluate the efficacy and safety of tislelizumab as second line treatment in participants with advanced unresectable/metastatic ESCC that had progressed during or after first line therapy.
Source references
- references
- citation
- Shen L, Kato K, Kim SB, Ajani JA, Zhao K, He Z, Yu X, Shu Y, Luo Q, Wang J, Chen Z, Niu Z, Zhang L, Yi T, Sun JM, Chen J, Yu G, Lin CY, Hara H, Bi Q, Satoh T, Pazo-Cid R, Arkenau HT, Borg C, Lordick F, Li L, Ding N, Tao A, Shi J, Van Cutsem E; RATIONALE-302 Investigators. Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study. J Clin Oncol. 2022 Sep 10;40(26):3065-3076. doi: 10.1200/JCO.21.01926. Epub 2022 Apr 20.
- pmid
- 35442766
- type
- RESULT
- citation
- Ajani JA, Wang K, Nikolaidis GF, Coaquira Castro J, Augusto Novis de Figueiredo M, Sun JM, Soulanis K, Tasoulas A, Zhan L. Comparative Efficacy and Safety of Tislelizumab in Second-Line Esophageal Squamous Cell Carcinoma: Systematic Literature Review and Simulated Treatment Comparisons. Adv Ther. 2026 Feb;43(2):567-582. doi: 10.1007/s12325-025-03410-5. Epub 2025 Dec 3.
- pmid
- 41335329
- type
- DERIVED
- 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
- 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.
- pmid
- 40179324
- type
- DERIVED
- citation
- 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.
- pmid
- 38414510
- type
- DERIVED
- citation
- Wang LL, Xie YX, Liu Y. Clinical efficacy and adverse reactions analysis of PD-1/PD-L1 inhibitors in advanced esophageal squamous cell carcinoma. Eur Rev Med Pharmacol Sci. 2024 Jan;28(2):659-667. doi: 10.26355/eurrev_202401_35062.
- pmid
- 38305608
- type
- DERIVED
- citation
- 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.
- pmid
- 38240916
- type
- DERIVED
- citation
- 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.
- pmid
- 37846080
- type
- DERIVED
- citation
- 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.
- pmid
- 35785595
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-252c6d8a07fb1d73a2d6
- requested nct id
- NCT03430843
- primary nct id
- NCT03430843
- source kind
- fda_spl_label
- source record id
- d46bfb2e-44c4-4a86-8a8f-b38fb01ac4b6
- source file sha256
- a9df7a5786dc51557d38f2a0881b5b5e9ae02ae396a6798e39ac96f586bcc5e6
- payload sha256
- fab02d74ff50684e82e66237dd043cebd99ca52c4abd891ea5071d24a7976fcb
- payload
- application numbers
- BLA761232
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-252c6d8a07fb1d73a2d6
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT03430843
- occurrences
- context exact
- ups detailed in Table 11 and Figure 1. Figure 1 Figure 2 Previously Treated Unresectable or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) RATIONALE-302 (NCT03430843) was a multicenter, randomized (1:1), open-label trial in 512 adult patients with unresectable advanced or metastatic ESCC who progressed on or after prior sys
- end
- 6103
- exact text
- NCT03430843
- start
- 6092
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/indications/raw/labels-00600.json
- source file sha256
- a9df7a5786dc51557d38f2a0881b5b5e9ae02ae396a6798e39ac96f586bcc5e6
- source json pointer
- /results/97/clinical_studies/0
- source kind
- fda_spl_label
- source record id
- d46bfb2e-44c4-4a86-8a8f-b38fb01ac4b6
- source string basis
- parsed_JSON_string_unmodified
- source string sha256
- 15faea2886b026151f646dd2eeefe6d66150d3fdf9a188603a25aacfa0f4ad2e
- spl effective time
- 20260831
- spl set id
- 08ef1e3e-496f-4b0b-94ee-fbba3cc1985a
Preserved source evidence · Not medical advice