A Phase 3, Randomized, Double-Blind Study of Ociperlimab, an Anti-TIGIT Antibody, in Combination With Tislelizumab Compared to Pembrolizumab in Patients With Previously Untreated, PD-L1-Selected, and Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 669
- 试验地点
- 384
- 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 ociperlimab + tislelizumab compared with that of pembrolizumab in adults with high levels of programmed cell death ligand-1 (PD-L1), locally advanced/recurrent or untreated metastatic non-small cell lung cancer (NSCLC).
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 or cytologically documented locally advanced or recurrent non-small cell lung cancer (NSCLC) that is not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, or metastatic-nonsquamous or squamous NSCLC.
- •No prior systemic treatment for metastatic NSCLC.
- •Agreement to provide archival tissue or fresh biopsy (if archival tissue is not available).
- •Tumors with PD-L1 expressed in ≥ 50% tumor cells.
- •At least 1 measurable lesion as defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤
排除标准
- •Known mutations in the epidermal growth factor receptor (EGFR) gene, anaplastic lymphoma kinase (ALK) fusion oncogene, BRAF V600E, or ROS
- •Prior therapy with an anti-programmed cell death protein (anti-PD)-1, anti-PD-ligand (L)-1, anti-PD-ligand-2, anti-T-cell immunoglobulin and ITIM (anti-TIGIT) domain, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
- •Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- •Active autoimmune diseases or history of autoimmune diseases that may relapse.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Arm B: Pembrolizumab plus Placebo
Participants received pembrolizumab 200 mg and placebo intravenously every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Placebo (Drug)
Arm C: Tislelizumab plus Placebo
Participants received tislelizumab 200 mg and placebo intravenously every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Placebo (Drug)
Arm B: Pembrolizumab plus Placebo
Participants received pembrolizumab 200 mg and placebo intravenously every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Pembrolizumab (Drug)
Arm C: Tislelizumab plus Placebo
Participants received tislelizumab 200 mg and placebo intravenously every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Tislelizumab (Drug)
Arm A: Ociperlimab plus Tislelizumab
Participants received ociperlimab 900 mg and tislelizumab 200 mg intravenously every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Tislelizumab (Drug)
Arm A: Ociperlimab plus Tislelizumab
Participants received ociperlimab 900 mg and tislelizumab 200 mg intravenously every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Ociperlimab (Drug)
Safety Run-In Substudy
Japanese participants received ociperlimab 900 mg and tislelizumab 200 mg every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Tislelizumab (Drug)
Safety Run-In Substudy
Japanese participants received ociperlimab 900 mg and tislelizumab 200 mg every 3 weeks. Treatment continued until lack of benefit, unacceptable toxicity, or withdrawal for other reasons.
干预措施: Ociperlimab (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to approximately 58 months
OS will be defined as the time from the date of randomization to the date of death due to any cause.
Overall Survival (OS) in Arms A and B
时间窗: From randomization until the end of the study. Maximum time on study was 45.0 months
OS is defined as the time from the date of randomization to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method. OS was a pre-specified primary endpoint for Arms A and B only.
Safety Run-In Substudy: Number of Participants Experiencing Adverse Events (AEs)
时间窗: From first dose of study drug to 30 days after last dose. Maximum treatment duration was 12.45 months.
The severity of AEs was determined according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0). AEs were graded on a scale of Grade 1 to Grade 5, with Grade 1 being the least severe and Grade 5 being the most severe. An AE is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a study drug, whether considered related to study drug or not. A serious adverse event (SAE) is any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, was considered a significant medical AE by the investigator based on medical judgement.
Safety Run-In Substudy: Serum Concentration of Ociperlimab
时间窗: Cycle 1 Day 1 (C1D1) Postdose (30 minutes after end of infusion), 24 and 72 Hours Postdose; C1D8; C1D15; C2D1 Predose and Postdose; C5D1 Predose; C5D1 Postdose; C5D8; C5D15; C6D1 Predose and Postdose; C9D1 Predose; C13D1 Predose; End of Treatment.
次要结局
- Progression-free Survival (PFS) As Assessed By Investigators(Up to approximately 58 months)
- Overall Response Rate (ORR) As Assessed By Investigators(Up to approximately 58 months)
- Duration Of Response (DOR) As Assessed By Investigators(Up to approximately 58 months)
- Health-related Quality Of Life (HRQoL): European Organization For Research And Treatment Of Cancer Quality Of Life Questionnaire Core 30 (EORTC QLQ-C30)(Within 7 days after permanent treatment discontinuation)
- HRQoL: EORTC Lung Cancer Module Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13) HRQoL will be assessed via PRO using the EORTC QLQ-LC13.(Within 7 days after permanent treatment discontinuation)
- HRQoL: European Quality of Life-5 Level- 5 Dimension (EQ-5D-5L) Questionnaire(Within 7 days after permanent treatment discontinuation)
- Time To Deterioration (TTD)(Within 7 days after permanent treatment discontinuation)
- Number Of Participants Experiencing Adverse Events (AEs)(90 days (±14) after last dose)
- Duration Of Response (DOR) for Arm A Versus Arm B As Assessed By the Investigator(Up to 45.0 months)
- Progression-free Survival (PFS) for Arm A Versus Arm B As Assessed By the Investigator(Up to 45.0 months)
- Progression-free Survival (PFS) for Safety Run-In Substudy As Assessed By the Investigator(Up to 38.9 months)
- Overall Response Rate (ORR) for Arm A Versus Arm B As Assessed By the Investigator(Response was assessed every 9 weeks from randomization for the first 52 weeks and then every 12 weeks thereafter, up to 45.0 months)
- Overall Response Rate (ORR) for Safety Run-In Substudy As Assessed By the Investigator(Response was assessed every 9 weeks from randomization for the first 52 weeks and then every 12 weeks thereafter, up to 38.9 months)
- Duration Of Response (DOR) for Safety Run-In Substudy As Assessed By the Investigator(Up to 38.9 months)
- Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL), Physical Functioning, and Pain Scores: European Organization For Research And Treatment Of Cancer Quality Of Life Questionnaire Core 30 (EORTC QLQ-C30) in Arms A and B(Baseline to Cycle 5 and Cycle 7, each cycle was 3 weeks)
- Change From Baseline in EORTC Lung Cancer Module Quality of Life Questionnaire Lung Cancer 13 (QLQ-LC13) Index Score, Dyspnea, Coughing, Hemoptysis, Pain in Chest, Pain in Arms/Shoulders, and Peripheral Neuropathy Scores in Arms A and B(Baseline to Cycle 5 and Cycle 7, each cycle was 3 weeks)
- Change From Baseline in European Quality of Life-5 Level- 5 Dimension (EQ-5D-5L) Visual Analog Scale in Arms A and B(Baseline to Cycle 5 and Cycle 7, each cycle was 3 weeks)
- Time To Deterioration (TTD) in Arms A and B Based on QLQ-LC13 Index Score, Cough, Chest Pain, Dyspnea, Hemoptysis, Arm or Shoulder Pain, and Peripheral Neuropathy(Up to 45.0 months)
- Time To Deterioration (TTD) in Arms A and B Based on QLQ-C30 GHS/QoL Score, Physical Functioning, and Fatigue(Up to 45.0 months)
- Number Of Participants Experiencing Adverse Events (AEs) in Arm A(From first dose of study drug up to 30 days after last dose (or 90 days for immune-mediated AEs); maximum treatment duration was 45.0 months)
- Safety Run-In Substudy: Participants With Anti-Drug Antibodies(Up to 38.9 months)