A Phase 2, Multicenter, Randomized, Placebo-Controlled Study to Compare the Efficacy of Anti-PD-1 Monoclonal Antibody Tislelizumab (BGB-A317) Plus Anti-TIGIT Monoclonal Antibody Ociperlimab (BGB-A1217) Versus Tislelizumab Plus Placebo as Second-Line Treatment in Patients With PD-L1 Tumor Area Positivity (TAP) ≥ 10% Unresectable, Locally Advanced, Recurrent or Metastatic Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 125
- 试验地点
- 86
- 主要终点
- Objective Response Rate (ORR) Assessed by the Investigator
研究概览
简要总结
A study of tislelizumab (BGB-A317) plus ociperlimab versus tislelizumab plus placebo as second-line treatment in participants with programmed cell death protein-ligand 1 (PD-L1) tumor area positivity (TAP) ≥ 10% unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.
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
- Triple (Participant, Care Provider, 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
- •Histologically confirmed diagnosis of esophageal squamous cell carcinoma (ESCC).
- •Have progressive disease during or after first-line of systemic treatment for unresectable, locally advanced, recurrent or metastatic ESCC.
- •Have measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Have confirmed programmed cell death protein-ligand 1 (PD-L1) tumor area positivity (TAP) ≥ 10% in tumor tissues tested by the central lab.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
排除标准
- •Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
- •Participants with evidence of fistula (either esophageal/bronchial or esophageal/aorta).
- •Evidence of complete esophageal obstruction not amenable to treatment.
- •Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks after intervention).
- •Has received any chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin, etc) or any investigational therapies within 14 days or 5 half-lives (whichever is longer) before the first dose of study drug. Or has received palliative radiation treatment or other local regional therapies within 14 days before the first dose of study drug.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm A: Tislelizumab plus Ociperlimab
Participants received 200 milligrams (mg) tislelizumab plus 900 mg ociperlimab intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.
干预措施: Tislelizumab (Biological)
Arm A: Tislelizumab plus Ociperlimab
Participants received 200 milligrams (mg) tislelizumab plus 900 mg ociperlimab intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.
干预措施: Ociperlimab (Biological)
Arm B: Tislelizumab plus Placebo
Participants received 200 mg tislelizumab plus placebo intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.
干预措施: Tislelizumab (Biological)
Arm B: Tislelizumab plus Placebo
Participants received 200 mg tislelizumab plus placebo intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of informed consent, whichever occurred first.
干预措施: Placebo (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Assessed by the Investigator
时间窗: Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.
Objective response rate is defined as the percentage of participants who had a best overall response of confirmed complete response (CR) or partial response (PR) assessed by the Investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Response evaluations were performed using computed tomography or magnetic resonance imaging (MRI) approximately every 6 weeks for the first 54 weeks and then every 12 weeks thereafter. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) \< 10 mm, and no new lesions. PR: At least a 30% decrease in the size of target lesions, with no progression of non-target lesions and no new lesions, or disappearance of target lesions with persistence of 1 or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions. Response (CR or PR) must have been confirmed 4 weeks or later after the first response was observed.
次要结局
- Overall Survival(From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.)
- Objective Response Rate Assessed by the Independent Review Committee(Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.)
- Progression-free Survival (PFS) Assessed by the Independent Review Committee(From randomization up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.)
- Progression-free Survival (PFS) Assessed by the Investigator(From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.)
- Duration Of Response (DOR) Assessed by the Independent Review Committee(From randomization up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.)
- Duration Of Response (DOR) Assessed by the Investigator(From randomization to the end of the study, median (range) time on follow-up was 10.0 (0.5 - 29.9) months in Arm A and 7.8 (0.4 - 29.3) months in Arm B.)
- Disease Control Rate Assessed by the IRC And the Investigator(Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.)
- Clinical Benefit Rate Assessed by the IRC and the Investigator(Up to the primary analysis data cutoff date of 01 February 2023; median (range) time on follow-up was 7.4 (0.5 - 20.1) months in Arm A and 6.4 (0.4 - 20.2) months in Arm B.)
- Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) and Physical Functioning Scores(Baseline, Cycle 5 Day 1 and Cycle 7 Day 1 (each cycle was 3 weeks))
- Change From Baseline in EORTC Quality of Life Oesophageal Cancer Questionnaires 18 (QLQ-OES18) Dysphagia, Eating, Reflux and Pain Scales(Baseline, Cycle 5 Day 1 and Cycle 7 Day 1 (each cycle was 3 weeks))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From first dose of study drug until 30 days after last dose; median duration of treatment was 3.45 months in Tislelizumab + Ociperlimab arm and 2.79 months in the Tislelizumab + Placebo arm.)