A Two-Part Randomized, Phase 3 Study of Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in First-line Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 789
- 试验地点
- 136
- 主要终点
- Overall survival
研究概览
简要总结
The primary objectives of this study are:
Part 1: To compare the overall survival (OS) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus platinum-based doublet chemotherapy in the first-line treatment of patients with advanced squamous or nonsquamous non-small cell lung cancer (NSCLC) with tumors expressing PD-L1 in <50% of tumor cells.
Part 2: To compare the OS of cemiplimab/chemo-f with placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.
The key secondary objectives are:
Part 1: To compare the progression-free survival (PFS) and objective response rate (ORR) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC and tumors expressing PD-L1 in <50% of tumor cells.
Part 2: To compare the PFS and ORR of cemiplimab/chemo-f versus placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part 1: Open label Part 2: Double blind
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
- •Men and women ≥20 years of age for Japanese patients
- •Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or IIIC disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease if they have not received prior systemic treatment for recurrent or metastatic NSCLC
- •Availability of an archival (≤5 months) or on-study obtained formalin-fixed, paraffin-embedded tumor tissue sample from a metastatic or recurrent site, which has not previously been irradiated
- •Part 1 only: Expression of PD-L1 in <50% of tumor cells determined by a commercially available assay performed by the central laboratory
- •At least 1 radiographically measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
- •Anticipated life expectancy of at least 3 months
排除标准
- •Part 1 only: Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime
- •Active or untreated brain metastases or spinal cord compression
- •Patients with tumors tested positive for Epidermal growth factor receptor (EGFR) gene mutations, Anaplastic lymphoma kinase (ALK) gene translocations, or C-ros oncogene receptor tyrosine kinase(ROS1) fusions
- •Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment
- •History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing pneumonia), of active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management, or of pneumonitis within the last 5 years
- •Ongoing or recent evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk of immune-related treatment-emergent adverse events (irTEAEs)
- •Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Placebo+Chemo
Part 2: Placebo plus chemo
干预措施: Placebo (Drug)
Chemo
Part 1: Chemotherapy
干预措施: Chemotherapy (Other)
REGN2810+AbbrevChemo+ipi
Part 1: REGN2810+abbrev chemo+ipi
干预措施: REGN2810/chemo/ipi (Drug)
REGN2810+Chemo Part 1
Part 1: REGN2810+chemo
干预措施: REGN2810 (Drug)
REGN2810+Chemo Part 2
Part 2: REGN2810+chemo
干预措施: REGN2810 (Drug)
Chemo
Part 1: Chemotherapy
干预措施: Placebo (Drug)
结局指标
主要结局
Overall survival
时间窗: Up to 32 months
Part 1: Overall Survival (OS)
时间窗: Up to a maximum of 82.2 months
OS was defined as the time from randomization to the date of death due to any cause.
Part 2: OS
时间窗: Up to a maximum of 68.4 months
OS was defined as the time from randomization to the date of death due to any cause.
次要结局
- Progression-free survival(Up to 32 months)
- Duration of Response (DOR)(Up to 32 months)
- Incidence of Treatment-emergent adverse events (TEAEs)(Up to 32 months)
- Incidence of serious adverse events (SAEs)(Up to 32 months)
- Overall survival rate(24 months)
- Best overall response (BOR)(Up to 32 months)
- Objective response rate(Up to 32 months)
- Incidence of Dose-limiting toxicities (DLTs)(Up to 32 months)
- Incidence of laboratory abnormalities(Up to 32 months)
- Incidence of deaths(Up to 32 months)
- Quality of life as measured by EORTC QLQ-LC13(Up to 32 months)
- Quality of life as measured by EORTC QLQ-C30(Up to 32 months)
- Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)(28 days)
- Part 1: Progression-free Survival (PFS) Per Independent Review Committee (IRC)(Up to a maximum of 82.2 months)
- Part 2: PFS Per IRC(Up to a maximum of 68.4 months)
- Part 1: Objective Response Rate (ORR) Per IRC(Up to 32 months)
- Part 2: ORR Per IRC(Up to 32 months)
- Part 1: Duration of Response (DoR)(Up to 32 months)
- Part 2: DoR(Up to 32 months)
- Part 1: Best Overall Response (BOR) Per IRC(Up to 32 months)
- Part 2: BOR Per IRC(Up to 32 months)
- Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From first dose of study drug in Part 1, up to approximately 83 months)
- Part 2: Number of Participants With TEAEs(From first dose of study drug in Part 2, up to approximately 69 months)
- Part 1: Number of Participants With Serious TEAEs(From first dose of study drug in Part 1, up to approximately 83 months)
- Part 2: Number of Participants With Serious TEAEs(From first dose of study drug in Part 2, up to approximately 69 months)
- Part 1: Number of Deaths During the On-Treatment Period(Up to 28 months)
- Part 2: Number of Deaths During the On-Treatment Period(Up to 28 months)
- Part 1: Estimated Survival Probability(12 months, 18 months, 24 months)
- Part 2: Estimated Survival Probability(12 months, 18 months, 24 months)
- Part 1: Change From Baseline in Global Health Status Score as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline, Day 1 of 21-Day Cycles 2, 3, 4, 5, 6, 9, 12, 15, 18, 19, 20, 21, 22, 23, 24, 27, 30, 33, 36, 39, 40, 42, 45, 48, 51, 54, 57, 60, 63, 66; Follow-up visit 1 (14 to 30 days after last study treatment) then continued follow-up every 3 months)
- Part 2: Change From Baseline in Global Health Status Score as Measured by the EORTC QLQ-C30(Baseline, Day 1 of 21-Day Cycles 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36; Follow-up 1 (14 to 30 days after last study treatment))