A Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific Antibody) Administered in Combination With Other Agents in MUC16 + Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 612
- 试验地点
- 52
- 主要终点
- Incidence of Dose Limiting Toxicities (DLT)
研究概览
简要总结
This study is researching an investigational drug called REGN5668 :
- alone or,
- combined with cemiplimab (also known as REGN2810) or,
- combined with both cemiplimab and fianlimab (also known as REGN3767), or
- combined with ubamatamab (also known as REGN4018), with or without sarilumab.
The main purposes of this study are to:
- Learn about the safety and profile of any side effects from the study drugs and to determine the highest, safe dose that can be given to participants with ovarian cancer or cancer of the uterus
- Look for signs that the study drugs can treat ovarian cancer or cancer of the uterus
This study has 2 parts. The purpose of Part 1 (Escalation) is to find the highest, safe dose of the study drug(s). The purpose of Part 2 (Expansion) is to use the doses chosen in Part 1. Participants with cancer of the uterus will only participate in Part 2.
The study is looking at several other research questions, including:
- Side effects that may be experienced by participants taking REGN5668 alone and/or in combination with cemiplimab, cemiplimab and fianlimab, or ubamatamab
- How REGN5668 works in the body either alone and/or in combination with cemiplimab, cemiplimab and fianlimab, or ubamatamab
- How much of the study drugs (REGN5668, cemiplimab, fianlimab, ubamatamab) are in the blood
- To see if REGN5668 in combination with cemiplimab, cemiplimab and fianlimab, or ubamatamab works to treat cancer
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Ovarian Cancer Cohorts Only: Has histologically or cytologically confirmed diagnosis of advanced epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer that has received at least 1 line of platinum-based systemic therapy as defined in the protocol
- •Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1 as described in the protocol.
- •Has a serum CA-125 level ≥2x ULN (in screening, not applicable to endometrial cohorts)
- •Has adequate organ and bone marrow function as defined in the protocol
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Has a life expectancy of at least 3 months
- •Endometrial Cancer Cohorts Only: histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-PD-1 therapy and platinum-based chemotherapy as described in the protocol
排除标准
- •Current or recent (as defined in the protocol) treatment with an investigational agent, systemic biologic therapy, or anti-cancer immunotherapy
- •Has had another malignancy within the last 5 years that is progressing, requires active treatment, or has a high likelihood of recurrence as defined in the protocol
- •Prior treatment with a Mucin 16 (MUC16)-targeted therapy
- •Ovarian Expansion cohorts only: More than 5 prior lines of systemic therapy
- •Has any condition that requires ongoing/continuous corticosteroid therapy as defined in the protocol within 1 week prior to the first dose of study drug
- •Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol
- •Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
- •Has history of clinically significant cardiovascular disease as defined in the protocol
- •Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s).
- •Note: Other protocol-defined Inclusion/Exclusion criteria apply
研究组 & 干预措施
Module 2
REGN5668 and ubamatamab
干预措施: REGN5668 (Drug)
Module 1
REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab
干预措施: Cemiplimab (Drug)
Module 1
REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab
干预措施: Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)] (Drug)
Module 2
REGN5668 and ubamatamab
干预措施: Ubamatamab (Drug)
Module 1
REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab
干预措施: REGN5668 (Drug)
Module 2
REGN5668 and ubamatamab
干预措施: Sarilumab (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLT)
时间窗: 42 days
Dose escalation phase, Module 1
Incidence of DLTs
时间窗: 21 days post combination administration
Dose escalation phase, Module 2
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Through study completion, up to 5 years
Primary: Dose escalation phase Secondary: Dose expansion phase
Incidence of Serious Adverse Events (SAEs)
时间窗: Through study completion, up to 5 years
Primary: Dose escalation phase Secondary: Dose expansion phase
Incidence of deaths
时间窗: Through study completion, up to 5 years
Primary: Dose escalation phase Secondary: Dose expansion phase
Incidence of laboratory abnormalities (Grade 3 or higher per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0 [v5.0])
时间窗: Through study completion, up to 5 years
Primary: Dose escalation phase Secondary: Dose expansion phase
Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or ubamatamab
时间窗: Through study completion, up to 5 years
Primary: Dose escalation phase
Objective Response Rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Eisenhauer, 2009) of REGN5668 in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination)
时间窗: Through study completion, up to 5 years
Primary: Dose expansion phase
Incidence of deaths
时间窗: Through study completion, up to 5 years
Primary: Dose escalation phase Secondary: Dose expansion phase
Incidence of laboratory abnormalities (Grade 3 or higher per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0 [v5.0])
时间窗: Through study completion, up to 5 years
Primary: Dose escalation phase Secondary: Dose expansion phase
Incidence of DLTs
时间窗: 21 days post combination administration
Dose escalation phase, Module 2
次要结局
- ORR based on RECIST 1.1(Through study completion, up to 5 years)
- Best Overall Response (BOR) based on RECIST 1.1(Through study completion, up to 5 years)
- Duration Of Response (DOR) based on RECIST 1.1(Through study completion, up to 5 years)
- Disease Control Rate (DCR) based on RECIST 1.1(Through study completion, up to 5 years)
- Progression-Free Survival (PFS) based on RECIST 1.1(Through study completion, up to 5 years)
- Cancer Antigen 125 (CA-125) change from baseline after treatment with REGN5668 in combinations with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination)(Through study completion, up to 5 years)
- Concentration of REGN5668 in serum over time when dosed alone and in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab(Through study completion, up to 5 years)
- Presence or absence of anti-drug antibodies against REGN5668(Through study completion, up to 5 years)
- Presence or absence of anti-drug antibodies against ubamatamab(Through study completion, up to 5 years)
- Presence or absence of anti-drug antibodies against cemiplimab(Through study completion, up to 5 years)
- Presence or absence of anti-drug antibodies against fianlimab(Through study completion, up to 5 years)
- Presence or absence of anti-drug antibodies against REGN5668(Through study completion, up to 5 years)
- Presence or absence of anti-drug antibodies against cemiplimab(Through study completion, up to 5 years)