A Randomized, Placebo-Controlled, Double-Blind Phase 3 Study to Evaluate the Efficacy and Safety of Tislelizumab (BGB-A317) in Combination With Chemotherapy as First-Line Treatment in Patients With Unresectable, Locally Advanced Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 649
- 试验地点
- 124
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Tislelizumab + Chemotherapy
Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Cisplatin (Drug)
Tislelizumab + Chemotherapy
Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Oxaliplatin (Drug)
Tislelizumab + Chemotherapy
Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Fluorouracil (5-FU) (Drug)
Tislelizumab + Chemotherapy
Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Capecitabine (Drug)
Tislelizumab + Chemotherapy
Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Paclitaxel (Drug)
Tislelizumab + Chemotherapy
Participants received tislelizumab 200 milligrams (mg) administered intravenously (IV) on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Tislelizumab (Biological)
Placebo + Chemotherapy
Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Cisplatin (Drug)
Placebo + Chemotherapy
Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Oxaliplatin (Drug)
Placebo + Chemotherapy
Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Fluorouracil (5-FU) (Drug)
Placebo + Chemotherapy
Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Capecitabine (Drug)
Placebo + Chemotherapy
Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Paclitaxel (Drug)
Placebo + Chemotherapy
Participants received placebo administered IV on Day 1 of each 3-week treatment cycle together with an investigator-chosen chemotherapy doublet until unacceptable toxicity, disease progression or withdrawal for other reasons.
Chemotherapy options were a platinum agent (cisplatin 60-80 mg/m² intravenously on Day 1 or oxaliplatin 130 mg/m² intravenously on Day 1) combined with a fluoropyrimidine (fluorouracil [750-800 mg/m² intravenously on Days 1-5] or capecitabine [1000 mg/m² orally twice daily on Days 1-14]) or paclitaxel (175 mg/m² intravenously on Day 1).
干预措施: Placebo (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.
Overall survival is defined as the time from the date of randomization until the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. Primary analysis (data cut-off date of 28 February 2022) was the pre-defined analysis at which the primary endpoint was tested for superiority.
次要结局
- Progression-Free Survival (PFS)(From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.)
- Objective Response Rate (ORR)(Response was assessed every 6 weeks for the first 48 weeks, then every 9 weeks thereafter; up to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.)
- Overall Survival (OS) in Participants With a PD-L1 Score ≥ 10%(From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.)
- Duration of Response (DOR)(From randomization to the primary analysis cutoff date of 28 February 2022; maximum time on follow-up was 3 years and 2 months.)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Oesophageal Cancer 18 Question Module (QLQ-OES18) Dysphagia, Eating, Reflux, Pain, and Index Scores(Baseline, Cycle 6 (Week 15))
- Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) and Physical Functioning Scales(Baseline, Cycle 6 (Week 15))
- Change From Baseline in EORTC QLQ-C30 Fatigue Scale(Baseline, Cycle 6 (Week 15))
- Change From Baseline in European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Visual Analog Scale (VAS)(Baseline, Cycle 6 (Week 15))
- Number of Participants Experiencing Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)(From first dose of study drug up to 30 days after last dose; maximum time on treatment was 63.5 months.)