Study of Tislelizumab (BGB-A317) Versus Placebo in Combination With Chemoradiotherapy in Participant With ESCC

• ClinicalTrials.gov Identifier: NCT03957590
• Recruitment Status: Active, not recruiting
• First Posted: May 21, 2019
• Last Update Posted: March 2, 2022
• Sponsor: BeiGene
• Information provided by (Responsible Party): BeiGene

Tracking Information

• First Submitted Date: May 16, 2019
• First Posted Date: May 21, 2019
• Last Update Posted Date: March 2, 2022
• Actual Study Start Date: June 12, 2019
• Actual Primary Completion Date: May 27, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 20, 2019): Progression-free survival (PFS) [ Time Frame: From date of randomization up to 4 years, approximately ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 14, 2020)

• overall response rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately ]
• duration of response (DOR) [ Time Frame: From first determination of an objective response up to 4 years, approximately ]
• overall survival (OS) [ Time Frame: From date of randomization up to 4 years, approximately ]
• change from baseline in European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30). [ Time Frame: From date of randomization to end of treatment ~2 years, ]
  Scale consultant including to assess Global health status/Qol with range from minimum scores 1 as worse outcome and maximum scores 7 as higher values represent a better, Physical functioning, role functioning, Emotional functioning, Cognitive functioning, social functioning, fatigue, nausea and vomiting, pain dyspnoea, insomnia, appetite loss, constipation, diarrhea and finical difficulties with range from maximum scores 4 as worse outcome and from minimum scores 1 as higher values represent as better.
• change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer module (EORTC QLQ-OES18). [ Time Frame: From date of randomization to end of treatment, ~2years ]
  Total 18 questions to assess your symptoms or problems during the past week with the range from minimum scores 1 as better outcome and maximum 4 as worst outcomes. includes whether any difficult to eat solids, liquids food or not， whether it is difficult to swallow ， whether the sense of smell and conversation are normal or not， whether have Symptoms include cough, indigestion or heartburn, acid reflux and pain or not .
• The incidence and severity of treatment-emergent adverse events (TEAEs) graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events'. [ Time Frame: From date of enrollment up to 4 years, approximately. ]

Original Secondary Outcome Measures (submitted: May 20, 2019)

• overall response rate (ORR) [ Time Frame: From date of randomization up to 4 years, approximately ]
• duration of response (DOR) [ Time Frame: From first determination of an objective response up to 4 years, approximately ]
• overall survival (OS) [ Time Frame: From date of randomization up to 4 years, approximately ]
• Health-related quality of life (HRQoL) assessed by EORTC QTQ-30 [ Time Frame: At screening or baseline up to 4 years, approximately ]
• Health-related quality of life (HRQoL) assessed by EORTC QTQ-OES18 [ Time Frame: At screening or baseline up to 4 years, approximately ]
• The incidence and severity of treatment-emergent adverse events (TEAEs) graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events'. [ Time Frame: From date of enrollment up to 4 years, approximately. ]

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

Descriptive Information

• Brief Title: Study of Tislelizumab (BGB-A317) Versus Placebo in Combination With Chemoradiotherapy in Participant With ESCC
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Tislelizumab (BGB-A317) Versus Placebo in Combination With Concurrent Chemoradiotherapy in Patients With Localized Esophageal Squamous Cell Carcinoma
• Brief Summary: This is a phase 3, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of BGB-A317 versus P placebo with chemoradiotherapy in participants with Localized Esophageal Squamous Cell Carcinoma.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Esophageal Squamous Cell Carcinoma (ESCC)

Intervention

• Drug: Tislelizumab
  Administrated at dose of 200 mg intravenously (IV)
  Other Name: BGB-A317
• Drug: Placebo
  Placebo to match tislelizumab
• Drug: Paclitaxel
  Administered as 135 mg/m² IV injection
• Drug: Cisplatin
  Administered as 25 mg/m² IV injection
• Radiation: Radiotherapy
  Administered at a total dose of 50.4 Gy in 28 fractions

Study Arms

• Experimental: Tislelizumab + chemoradiotherapy
  Tislelizumab once every 3-week cycle (Q3W) + paclitaxel on Day 1 of every cycle, for a total of 2 cycles + cisplatin on Day 1 to 3 of every cycle (3 weeks), for a total of 2 cycles + Radiotherapy
  Interventions:

  • Drug: Tislelizumab
  • Drug: Paclitaxel
  • Drug: Cisplatin
  • Radiation: Radiotherapy
• Placebo Comparator: Placebo combined + chemoradiotherapy
  Placebo once every 3-week cycle (Q3W) + paclitaxel on Day 1 of every cycle, for a total of 2 cycles + cisplatin on Day 1 to 3 of every cycle (3 weeks), for a total of 2 cycles + Radiotherapy
  Interventions:

  • Drug: Placebo
  • Drug: Paclitaxel
  • Drug: Cisplatin
  • Radiation: Radiotherapy

• Publications *: Yu R, Wang W, Li T, Li J, Zhao K, Wang W, Liang L, Wu H, Ai T, Huang W, Li L, Yu W, Wei C, Wang Y, Shen W, Xiao Z. RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma. Future Oncol. 2021 Nov;17(31):4081-4089. doi: 10.2217/fon-2021-0632. Epub 2021 Jul 16.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 1, 2022): 370
• Original Estimated Enrollment (submitted: May 20, 2019): 316
• Estimated Study Completion Date: October 30, 2023
• Actual Primary Completion Date: May 27, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• 18 to 75 years on the day of signing the informed consent form
• Histologically confirmed diagnosis of localized ESCC
• Measurable and/or non-measurable disease defined per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
• Adequate organ function

Key Exclusion Criteria:

• Indicators of severe malnutrition
• Clinically uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention within 2 weeks prior to randomization
• Known to be intolerable or resistant to treatment with the protocol-specified chemotherapy
• Received prior radiotherapy or therapies targeting PD-1, PD-L1, PD-L2 or other immune-oncology therapies
• Active autoimmune diseases or history of autoimmune diseases that may relapse

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03957590
• Other Study ID Numbers: BGB-A317-311; CTR20190198 ( Registry Identifier: Center for drug evaluation, CFDA )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• Principal Investigator: Weihu Wang, MD; Peking University Cancer Hospital & Institute
• Principal Investigator: Zefen Xiao, MD; Cancer Institute and Hospital, Chinese Academy of Medical Sciences

• PRS Account: BeiGene
• Verification Date: March 2022