A Study of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First Line Treatment in Participants With Advanced Esophageal Squamous Cell Carcinoma
Phase 3
Completed
- Conditions
- Esophageal Squamous Cell Carcinoma (ESCC)
- Interventions
- Registration Number
- NCT03783442
- Lead Sponsor
- BeiGene
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 649
Inclusion Criteria
- Pathologically (histologically) confirmed diagnosis of ESCC
- 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
- Palliative radiation treatment for ESCC within 4 weeks of study treatment initiation
- Prior systemic therapy for unresectable, locally advanced recurrent or metastatic ESCC
- Received prior therapies targeting programmed cell death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1) or PD-L2
- Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta)
- 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)
- Evidence of complete esophageal obstruction not amenable to treatment
- Unintentional weight loss ≥ 5% within one month prior to randomization or Nutritional Risk Index (NRI) < 83.5 per investigator's choice
- Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Chemotherapy Placebo Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Tislelizumab + Chemotherapy Fluorouracil (5-FU) Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or * Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Placebo + Chemotherapy Fluorouracil (5-FU) Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Tislelizumab + Chemotherapy Oxaliplatin Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or * Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Tislelizumab + Chemotherapy Cisplatin Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or * Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Tislelizumab + Chemotherapy Capecitabine Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or * Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Tislelizumab + Chemotherapy Paclitaxel Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or * Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Tislelizumab + Chemotherapy Tislelizumab Tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or * Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Placebo + Chemotherapy Cisplatin Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Placebo + Chemotherapy Oxaliplatin Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Placebo + Chemotherapy Capecitabine Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines Placebo + Chemotherapy Paclitaxel Matched placebo administered IV on Day 1 of each cycle every 3 weeks (Q3W) plus one of the following until unacceptable toxicity, disease progression or withdrawal for other reasons; each cycle is 21 days * Chemotherapy Doublet A: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and 5-fluorouracil IV 750-800 mg/m\^2 on Days 1 to 5 of each cycle Q3W; * Chemotherapy Doublet B: cisplatin 60-80 mg/m\^2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and capecitabine orally 1000 mg/m\^2 on Days 1 to 14 of each cycle, twice a day; or Chemotherapy Doublet C: cisplatin 60-80 mg/m\^2 administered IV on Day 1 or 2 or oxaliplatin 130 mg/m\^2 administered IV on Day 1 of each cycle Q3W and paclitaxel 175 mg/m\^2 IV on Day 1 of each cycle Q3W; cisplatin may be given in 3 divided doses on Days 1, 2, and 3 depending on local guidelines
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to approximately 3 years and 2 months (as of primary analysis data cut-off date of 28FEB2022) OS is defined as the time from the date of randomization until the date of death due to any cause
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Approximately 40 months from date of the first participant randomization 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
Objective Response Rate (ORR) Approximately 40 months from date of the first participant randomization ORR is defined as the proportion of participants whose best overall response (BOR) is complete response (CR) or partial response (PR) assessed by the investigator per RECIST v1.1
Overall Survival (OS) in the PD-L1 Score ≥ 10% Subgroup Approximately 40 months from date of the first participant randomization OS is defined as the time from the date of randomization until the date of death due to any cause
Duration of Response (DOR) Approximately 40 months from date of the first participant randomization 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 comes first
Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using European Quality of Life-Core 30 Questionnaire Index (EORTC QLQ-C30) Approximately 40 months from date of the first participant randomization Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Esophageal Cancer Specific Module (EORTC QLQ-OES18) Approximately 40 months from date of the first participant randomization Health-Related Quality of Life (HRQoL) Assessment of the Participant's Overall Health Status Using the Generic Health State Instrument European Quality of Life-5 Dimensions (EuroQol 5D EQ-5D-5L) Approximately 40 months from date of the first participant randomization Number of Participants Experiencing Adverse Events (AEs) Approximately 40 months from date of the first participant randomization
Trial Locations
- Locations (176)
Smilow Cancer Hospital at Yale-New Haven - Neurology
🇺🇸New Haven, Connecticut, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Allegheny General Hospital (AGH)
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
University of Texas Health Science Center of San Antonio
🇺🇸San Antonio, Texas, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
Coffs Harbour Hospital
🇦🇺Coffs Harbour, Pacific Highway, Australia
Townsville Hospital
🇦🇺Douglas, Queensland, Australia
Ashford Cancer Centre Research
🇦🇺Kurralta Park, South Australia, Australia
Royal Hobart Hospital
🇦🇺Hobart, Tasmania, Australia
Scroll for more (166 remaining)Smilow Cancer Hospital at Yale-New Haven - Neurology🇺🇸New Haven, Connecticut, United States