A Phase 1, Open-Label, Dose-Escalation and Cohort Expansion First-in-Human Study of the Safety, Tolerability, Activity and Pharmacokinetics of REGN3767 (Anti-LAG-3 mAb) Administered Alone or in Combination With REGN2810 (Anti-PD-1 mAb) in Patients With Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 333
- 试验地点
- 43
- 主要终点
- Rate of dose limiting toxicities (Dose Escalation Phase)
研究概览
简要总结
The primary objectives in the dose escalation phase are to evaluate safety and pharmacokinetics (PK) in order to determine the selected dose level(s) for expansion of REGN3767 as monotherapy and in combination with cemiplimab in patients with advanced malignancies, including lymphoma.
The primary objectives in the dose expansion phase are to assess preliminary anti-tumor activity of REGN3767 alone and in combination with cemiplimab (separately by cohort) as measured by objective response rate (ORR).
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
- •Dose escalation cohorts: Patients with histologically or cytologically confirmed diagnosis of malignancy (including lymphoma) with demonstrated progression of a tumor for whom there is no available therapy likely to convey clinical benefit AND who have not been previously treated with a PD-1/PD-L1 inhibitor. These patients do not require measurable disease
- •Dose expansion cohorts: Patients with histologically or cytologically confirmed diagnosis of 1 of specified tumors with measurable disease per RECIST 1.1 or Lugano criteria. Some patients may have been previously treated with a PD-1 or PD-L1 inhibitor
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Adequate organ and bone marrow function
排除标准
- •Prior treatment with any LAG-3 targeting biologic or small molecule
- •Radiation therapy within 2 weeks prior to randomization and not recovered to baseline from any AE due to radiation
- •Untreated or active central nervous system metastases - Ongoing or recent (within 5 years) evidence of significant autoimmune disease
- •Corticosteroid therapy (>10 mg prednisone/day or equivalent) within 1 week prior to the first dose of study drug
- •Myocardial infarction within 6 months
- •Note: Other protocol defined Inclusion / Exclusion criteria apply
研究组 & 干预措施
Monotherapy (REGN3767)
Group A will consist of up to 4 sequential dose cohorts. Each cohort will receive 1 of 3 ascending dose levels of study drug during dose escalation. In addition 1 tumor-specific cohort will be treated at the recommended phase 2 dose (RP2D) during dose expansion.
干预措施: REGN3767 (Drug)
Combination Therapy (REGN3767+cemiplimab)
Group B will consist of up to 4 sequential dose cohorts. Each cohort will receive 1 of 3 ascending dose levels of study drug during dose escalation. In addition, 9 tumor-specific cohorts will be treated at the RP2D during dose expansion
干预措施: REGN3767 (Drug)
Combination Therapy (REGN3767+cemiplimab)
Group B will consist of up to 4 sequential dose cohorts. Each cohort will receive 1 of 3 ascending dose levels of study drug during dose escalation. In addition, 9 tumor-specific cohorts will be treated at the RP2D during dose expansion
干预措施: cemiplimab (Drug)
结局指标
主要结局
Rate of dose limiting toxicities (Dose Escalation Phase)
时间窗: Baseline to 28 days
AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
AUC from time zero extrapolated to infinity [AUCinf] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Rate of adverse events (Dose Escalation Phase)
时间窗: Baseline to 51 weeks
Rate of serious adverse events (Dose Escalation Phase)
时间窗: Baseline to 51 weeks
Occurrence of death (Dose Escalation Phase)
时间窗: Baseline to 51 weeks
AUC computed from time zero to the time of the last positive concentration [AUClast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Last positive (quantifiable) concentration [Clast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Observed terminal half-life [t1/2] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Escalation Phase)
时间窗: Baseline to 51 weeks
Area under the curve (AUC) computed from time zero to the time of the last concentration [AUCall] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
AUCall-to-dose ratio [AUCall/Dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
AUClast-to-dose ratio [AUClast/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Clearance [CL] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Maximum Plasma Concentration [Cmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to week 51
t1/2 beta (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Volume of distribution at steady state [Vss] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Cmax-to-dose ratio [Cmax/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Mean residence time extrapolated to infinity [MRTinf] (Dose Escalation Phase)
时间窗: Baseline to 51 weeks
Mean residence time when the drug concentration profile is based on values up to and including the last positive concentration [MRTlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Time to Cmax [tmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Volume of distribution of the terminal phase [Vz] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
时间窗: Baseline to 51 weeks
Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase)
时间窗: Baseline to 51 weeks
次要结局
- Progression free survival based on Lugano criteria (Dose Escalation Phase)(Baseline to 51 weeks)
- Incidence of adverse events (Dose Expansion Phase)(Baseline to 51 weeks)
- Disease control rate based on RECIST criteria (Dose Escalation Phase)(Baseline to 51 weeks)
- Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase)(Baseline to week 51)
- Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase)(Baseline to week 51)
- Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase)(Baseline to 51 weeks)
- Best overall response based on irRECIST criteria (Dose Escalation Phase)(Baseline to 51 weeks)
- Best overall response based on Lugano criteria (Dose Escalation Phase)(Baseline to 51 weeks)
- Duration of response based on RECIST criteria (Dose Escalation Phase)(Baseline to week 51)
- Duration of response based on irRECIST criteria (Dose Escalation Phase)(Baseline to week 51)
- Duration of response based on Lugano criteria (Dose Escalation Phase)(Baseline to week 51)
- Disease control rate based on Lugano criteria (Dose Escalation Phase)(Baseline to 51 weeks)
- Disease control rate based on irRECIST criteria (Dose Escalation Phase)(Baseline to 51 weeks)
- Progression free survival based on RECIST (Dose Escalation Phase)(Baseline to 51 weeks)
- Progression free survival based on irRECIST (Dose Escalation Phase)(Baseline to 51 weeks)
- Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase)(Baseline to 51 weeks)
- Incidence of serious adverse events (Dose Expansion Phase)(Baseline to 51 weeks)
- Incidence of death (Dose Expansion Phase)(From Baseline to the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 42 months)
- Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Expansion Phase)(Baseline to 51 weeks)