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

• ClinicalTrials.gov Identifier: NCT03430843
• Recruitment Status: Completed
• First Posted: February 13, 2018
• Results First Posted: December 29, 2023
• Last Update Posted: December 29, 2023
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: January 29, 2018
• First Posted Date: February 13, 2018
• Results First Submitted Date: November 10, 2023
• Results First Posted Date: December 29, 2023
• Last Update Posted Date: December 29, 2023
• Actual Study Start Date: January 26, 2018
• Actual Primary Completion Date: December 1, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 10, 2023)

Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set [ Time Frame: Approximately 2 years and 10 months from date of first randomization ]

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

Original Primary Outcome Measures (submitted: February 6, 2018)

Overall survival (OS) [ Time Frame: approximately 2 years from date of first randomization ]

Length of time from study treatment initiation to death of any cause

Current Secondary Outcome Measures (submitted: December 12, 2023)

• 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) ]
  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%.
• 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) ]
  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;
• 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) ]
  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;
• 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) ]
  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
• 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) ]
  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
• 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) ]
  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
• 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) ]
  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
• 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) ]
  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
• HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set [ Time Frame: Baseline to Cycle 6 (21 days per cycle) ]
  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
• 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) ]
  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.
• HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set. [ Time Frame: Baseline to Cycle 6 (21 days per cycle) ]
  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.
• 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) ]
  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.
• HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set [ Time Frame: Baseline to Cycle 6 (21 days per cycle) ]
  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.
• Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: From the first dose date to 30 days after the last dose date; up to approximately 4 years and 11 months ]
  Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs

Original Secondary Outcome Measures (submitted: February 6, 2018)

• Objective response rate (ORR) [ Time Frame: 2 years ]
  Clinical response rate of treatment (CR + PR) according to RECIST v1.1 criteria
• Progression-free survival (PFS) [ Time Frame: 2 years ]
  The interval from study treatment initiation until the determination of disease progression according to RECIST v1.1 criteria or death
• Duration of response (DOR) [ Time Frame: 2 years ]
  The interval from the date of the first response (complete response or partial response) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause
• The Health-Related Quality of Life Questionnaire [ Time Frame: 2 years ]
• Safety will be analyzed through the incidence of adverse events. [ Time Frame: From the first dose date to 30 days after the last dose date ]
• Safety will be analyzed through the incidence of immune-related adverse events. [ Time Frame: From the first dose date to 90 days after the last dose date ]
• Safety will be analyzed through the incidence of serious adverse events. [ Time Frame: From the first dose date to 30 days after the last dose date ]
• Safety will be analyzed through the incidence of laboratory abnormalities. [ Time Frame: From the first dose date to 30 days after the last dose date ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
• Official Title: A Randomized, Controlled, Open-label, Global Phase 3 Study Comparing the Efficacy of the Anti-PD-1 Antibody Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Patients With Advanced Unresectable/Metastatic Esophageal Squamous Cell Carcinoma
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Esophageal Squamous Cell Carcinoma (ESCC)

Intervention

• Drug: Tislelizumab
  200 mg administered intravenously (IV)
  Other Name: BGB-A317
• Drug: Paclitaxel
  135-175 mg /m² administered IV , or 80-100 mg/m^2 administered IV according to local guidelines for standard of care
• Drug: Docetaxel
  75 mg/m^2 administered IV or 70 mg/m^2 IV in Japan
• Drug: Irinotecan
  125 mg/m^2 administered IV

Study Arms

• Experimental: Tislelizumab
  Tislelizumab on Day 1, given every 21 days
  Intervention: Drug: Tislelizumab
• Active Comparator: Investigator chosen chemotherapy (ICC)
  Paclitaxel on Day 1, given every 21 days or on a weekly schedule; OR Docetaxel on Day 1, given every 21 days; OR Irinotecan on Days 1 and 8, given every 21 days
  Interventions:

  • Drug: Paclitaxel
  • Drug: Docetaxel
  • Drug: Irinotecan

Publications *

• 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. Erratum In: J Clin Oncol. 2024 Feb 1;42(4):486.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 10, 2023): 512
• Original Estimated Enrollment (submitted: February 6, 2018): 450
• Actual Study Completion Date: December 28, 2022
• Actual Primary Completion Date: December 1, 2020 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, China, France, Germany, Italy, Japan, Korea, Republic of, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT03430843
• Other Study ID Numbers: BGB-A317-302; 2017-003699-30 ( EudraCT Number ); CTR20171026 ( Registry Identifier: ChinaDrugTrials )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: BeiGene
• Original Responsible Party: Same as current
• Current Study Sponsor: BeiGene
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: BeiGene
• Verification Date: December 2023