A Phase 1/2a, Open-Label, Dose Escalation and Dose Expansion First-In-Human Study of the Safety, Tolerability, Activity, and Pharmacokinetics of REGN10597 (Anti-PD-1-IL-2RA-IL-2 Fusion Protein) Alone or in Combination With Cemiplimab in Patients With Advanced Solid Organ Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 22
- 主要终点
- Incidence of TEAEs leading to treatment discontinuation
研究概览
简要总结
This study is researching an experimental drug called REGN10597 alone or in combination with another drug called cemiplimab (called "study drug(s)"). The study is focused on patients with certain solid tumors that are in an advanced stage.
The aim of the study is to see how safe, tolerable, and effective the study drug(s) are.
The study is looking at several other research questions, including:
- What side effects may happen from taking the study drug(s)
- How much study drug(s) is in the blood at different times
- Whether the body makes antibodies against the study drug(s) (which could make the study drug(s) less effective or could lead to side effects)
详细描述
Phase 1: Conducted in the United States only Phase 2: Conducted globally
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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:
- •1. Histologically or cytologically confirmed diagnosis of solid malignancy (locally advanced or metastatic) with confirmed progression on standard-of-care therapy. Participants are required to submit archival tissue if it is available
- •Dose expansion cohorts:
- •1. Histologically of cytologically confirmed diagnosis of one of the following tumors with criteria, as defined in the protocol:
- •Module 1, Cohort 1: anti-PD-(L)1 Progressed Melanoma or
- •Module 1, Cohort 2: anti-PD-(L)1 Progressed RCC or
- •Module 2, Cohort 1: 1L Melanoma ALL Participants ARE REQUIRED to submit fresh pretreatment biopsy during screening, with an additional exploratory biopsy at other time points
排除标准
- •Prior treatment with Interleukin 2 (IL2)/IL15/IL-7 given outside the context of concurrent administration with adoptive cell therapy
- •Prior treatment with anti-PD1/PD-L1, or an approved systemic therapy or any previous systemic non-immunomodulatory biologic therapy within 4 weeks, as defined in the protocol
- •Has received radiation therapy or major surgery within 14 days prior to first dose of study drug or has not yet recovered from AEs
- •Has had prior anti-cancer immunotherapy within 4 weeks prior to study intervention, or discontinuation of prior anti-cancer immunotherapy due to grade 3 or 4 toxicities
- •Has ongoing immune-related AEs prior to initiation of study intervention, as defined in the protocol
- •Has known allergy or hypersensitivity to components of the study drug(s)
- •Has any condition requiring ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1-2 weeks to the first dose of study intervention
- •Has ongoing or recent (within 5 years) evidence of significant autoimmune disease or any other condition that required treatment with systemic immunosuppressive treatments
- •NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply.
研究组 & 干预措施
Phase 1: Monotherapy Dose Escalation
Multiple Dose Level (DL) Cohorts to identify the Recommended Phase 2 Dose (RP2D)
干预措施: REGN10597 (Drug)
Phase 2: Monotherapy Dose Expansion
Cohort 1: Melanoma participants Cohort 2: Clear-cell Renal-Cell Carcinoma (ccRCC) participants
干预措施: REGN10597 (Drug)
Phase 1: Combination Dose Escalation
Multiple DL Cohorts to identify the RP2D
干预措施: REGN10597 (Drug)
Phase 1: Combination Dose Escalation
Multiple DL Cohorts to identify the RP2D
干预措施: Cemiplimab (Drug)
Phase 2: Combination Dose Expansion
Cohort 1: Melanoma participants
干预措施: REGN10597 (Drug)
Phase 2: Combination Dose Expansion
Cohort 1: Melanoma participants
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Incidence of TEAEs leading to treatment discontinuation
时间窗: Approximately 6 Years
Dose escalation
Incidence of TEAEs leading to death
时间窗: Approximately 6 Years
Dose escalation
Incidence of TEAEs leading to death
时间窗: Approximately 6 Years
Dose escalation
Incidence of Dose-Limiting Toxicities (DLTs)
时间窗: Up to Day 29
Dose escalation
Incidence of Treatment-Emergent Adverse Event (TEAEs)
时间窗: Approximately 6 Years
Dose escalation
Incidence of Serious Adverse Events (SAEs)
时间窗: Approximately 6 Years
Dose escalation
Incidence of TEAEs leading to treatment discontinuation
时间窗: Approximately 6 Years
Dose escalation
Number of participants with Grade 3 laboratory abnormalities
时间窗: Approximately 6 Years
Dose escalation Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria by investigator assessment
时间窗: Approximately 6 Years
Dose expansion
次要结局
- ORR based on RECIST 1.1 criteria by investigator assessment(Approximately 6 Years)
- Disease control rate based on RECIST 1.1(Approximately 6 Years)
- Time to response based on RECIST 1.1(Approximately 6 Years)
- Concentrations of REGN10597 in serum(Approximately 6 Years)
- ORR based on RECIST 1.1 criteria by investigator assessment(Approximately 6 Years)
- Best Overall Response (BOR) based on RECIST 1.1 criteria(Approximately 6 Years)
- Duration Of Response (DOR) based on RECIST 1.1 criteria(Approximately 6 Years)
- Disease control rate based on RECIST 1.1(Approximately 6 Years)
- Time to response based on RECIST 1.1(Approximately 6 Years)
- Progression Free Survival (PFS) based on RECIST 1.1(Approximately 6 Years)
- Concentrations of REGN10597 in serum(Approximately 6 Years)
- Incidence of Anti-Drug Antibody (ADA) to REGN10597 over time(Approximately 6 Years)
- Magnitude of ADA to REGN10597 over time(Approximately 6 Years)