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
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- BeiGene
- Enrollment
- 370
- Locations
- 55
- Primary Endpoint
- Progression-free Survival (PFS)
Overview
Brief Summary
This is a phase 3, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of tislelizumab (BGB-A317) versus placebo in combination with chemoradiotherapy in participants with localized esophageal squamous cell carcinoma (ESCC).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically confirmed diagnosis of localized ESCC and suitable for concurrent chemoradiotherapy (cCRT)
- •Measurable and/or non-measurable disease defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- •Adequate organ function
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 programmed cell death protein-1 (PD-1), programmed cell death protein ligand-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.
Arms & Interventions
Tislelizumab + Chemoradiotherapy
Participants received 200 mg tislelizumab administered intravenously (IV) once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by 200 mg tislelizumab for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Radiotherapy (Radiation)
Placebo + Chemoradiotherapy
Participants received placebo IV once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by placebo for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Placebo (Drug)
Placebo + Chemoradiotherapy
Participants received placebo IV once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by placebo for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Radiotherapy (Radiation)
Placebo + Chemoradiotherapy
Participants received placebo IV once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by placebo for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Cisplatin (Drug)
Tislelizumab + Chemoradiotherapy
Participants received 200 mg tislelizumab administered intravenously (IV) once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by 200 mg tislelizumab for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Cisplatin (Drug)
Tislelizumab + Chemoradiotherapy
Participants received 200 mg tislelizumab administered intravenously (IV) once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by 200 mg tislelizumab for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Tislelizumab (Drug)
Tislelizumab + Chemoradiotherapy
Participants received 200 mg tislelizumab administered intravenously (IV) once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by 200 mg tislelizumab for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Paclitaxel (Drug)
Placebo + Chemoradiotherapy
Participants received placebo IV once every 3 weeks in combination with concurrent chemoradiotherapy (CRT) for up to approximately 6 weeks followed by placebo for a total of up to 24 months (about 35 cycles), or until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion was met, whichever occurred first.
Concurrent chemotherapy consisted of cisplatin (25 mg/m² IV; Days 1-3 of each 3-week cycle) in combination with paclitaxel (135 mg/m² IV; Day 1 of each 3-week cycle) and radiotherapy was delivered in 28 fractions (total dose, 50.4 Gy).
Intervention: Paclitaxel (Drug)
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: From randomization to the prespecified primary analysis data cut-off date of 08 January 2025; maximum time on study was 67 months.
PFS is defined as the time from randomization to the first documented disease progression, as determined by the Blinded Independent Review Committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurred first. PFS was estimated using the Kaplan-Meier method. Progressive Disease (PD): 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, and/or unequivocal progression of existing nontarget lesions. or the appearance of one or more new lesions.
Progression-free survival (PFS)
Time Frame: From date of randomization up to 4 years, approximately
PFS is- defined as the time from randomization to the first documented disease progression, as determined by the Blinded Independent Review Committee (BIRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurs first.
Secondary Outcomes
- Overall Survival (OS)(From randomization to the prespecified analysis data cut-off date of 08 January 2025; maximum time on study was 67 months.)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Oesophageal Cancer Module (OES18) Dysphagia, Reflux, Pain, and Eating Scales(Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days))
- Change From Baseline in EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL), Physical Functioning, and Fatigue Scores(Baseline and Cycle 6 and Cycle 10 (each cycle was 21 days))
- Overall Response Rate (ORR)(Tumor assessments occurred every 9 weeks for the first 54 weeks, and every 12 weeks during the next 2 years and every 24 weeks thereafter until radiographic disease progression or death; up to 67 months)
- Duration of Response (DOR)(Up to 67 months)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose of study drug to 30 days after last dose, maximum time on treatment was 57.5 months)
- Overall survival (OS)(From date of randomization up to 4 years, approximately)
- Change from baseline in European Quality of Life-Core 30 Questionnaire index (EORTC QLQ-C30)(Baseline to end of treatment ~2 years)
- Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire esophageal cancer module (EORTC QLQ-OES18)(Up to 2 years, approximately)
- Overall response rate (ORR)(From date of randomization up to 4 years, approximately)
- Duration of response (DOR)(From first determination of an objective response up to 4 years, approximately)
- Number of Participants with treatment-emergent adverse events (TEAEs)(Up to 2 years, approximately)