A Phase 1 Study of REGN4659 (Anti-CTLA-4 mAb) in Combination With Cemiplimab (Anti-PD-1 mAb) in the Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Rate of immune-related adverse events (irAEs)
研究概览
简要总结
The objective of this trial is to study REGN4659 and cemiplimab in treatment-experienced, non-small cell lung cancer (NSCLC) patients. There are 2 phases of this study: a dose escalation phase and a dose expansion phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients with histologically or cytologically documented squamous or non-squamous NSCLC with unresectable stage IIIB or stage IV disease
- •Combination dose escalation cohorts: Treatment-experienced patients who have received no more than 3 lines of systemic therapy including no more than 2 lines of cytotoxic chemotherapy, and for whom no available therapy has a high probability to convey clinical benefit.
- •Dose escalation cohort C: Anti-PD-1/PD-L1 naïve patients who have received 1 to 2 prior lines of cytotoxic chemotherapy including a platinum doublet-containing regimen
- •Expansion cohort(s): Anti-PD-1/PD-L1 experienced patients who have progressed while receiving therapy or within 6 months of stopping therapy for stage III or IV disease. Patients must not have permanently discontinued anti-PD-1/PD-L1 therapy due to treatment related AE. Patients must have received one line of anti-PD--1/PD-L1 immunotherapy. Patients may also have received one line of chemotherapy
排除标准
- •Expansion cohort(s) only: Patients who have never smoked, defined as smoking ≤100 cigarettes in a lifetime
- •Active or untreated brain metastases or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. Patients must be off (immunosuppressive doses of) corticosteroid therapy
- •Expansion cohort(s) only: Patients with tumors tested positive for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations or ROS1 fusions.
- •Radiation therapy within 2 weeks prior to enrollment and not recovered to baseline from any AE due to radiation
- •Patients who received prior treatment with an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody
- •Previous treatment with idelalisib (ZYDELIG®) at any time
- •Note: Other protocol defined inclusion/ exclusion criteria apply
研究组 & 干预措施
Cemiplimab Monotherapy
In a single dose escalation cohort, participants will receive cemiplimab alone.
干预措施: Cemiplimab (Drug)
Combination Therapy
Dose Escalation cohorts:
In 3 dose escalation cohorts, participants will receive a lead-in dose of REGN4659 followed by REGN4659 and cemiplimab in combination.
In 4 dose escalation cohorts, participants will receive REGN4659 with cemiplimab in combination.
Dose Expansion cohorts:
In dose expansion cohorts, participants will receive combination regimens of REGN4659 and cemiplimab.
干预措施: REGN4659 (Drug)
Combination Therapy
Dose Escalation cohorts:
In 3 dose escalation cohorts, participants will receive a lead-in dose of REGN4659 followed by REGN4659 and cemiplimab in combination.
In 4 dose escalation cohorts, participants will receive REGN4659 with cemiplimab in combination.
Dose Expansion cohorts:
In dose expansion cohorts, participants will receive combination regimens of REGN4659 and cemiplimab.
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Rate of immune-related adverse events (irAEs)
时间窗: Up to week 126
Rate of serious adverse events (SAEs)
时间窗: Up to week 126
Rate of deaths
时间窗: Up to week 126
Rate of dose limiting toxicities (DLTs) during the dose escalation phase
时间窗: Up to week 126
Rate of treatment emergent adverse events (TEAEs)
时间窗: Up to week 126
Laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE])
时间窗: Up to week 126
Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during the dose expansion phase
时间窗: Up to week 126
REGN4659 and cemiplimab concentrations in serum over time
时间窗: Up to week 126
次要结局
- ORR based on RECIST 1.1 during the dose escalation phase(Up to week 126)
- ORR based on immune-based therapy Response Evaluation Criteria (iRECIST)(Up to week 126)
- Best overall response (BOR)(Up to week 126)
- Disease control rate(Up to week 126)
- Progression-free-survival (PFS) based on RECIST 1.1(Up to week 126)
- PFS based on iRECIST(Up to week 126)
- Overall survival (OS)(Up to week 126)
- Duration of response (DOR)(Up to week 126)