A PHASE 1/2 STUDY OF REGN5668 (MUC16 × CD28, A COSTIMULATORY BISPECIFIC ANTIBODY) ADMINISTERED IN COMBINATION WITH OTHER AGENTS IN MUC16+ MALIGNANCIES
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 191
- 试验地点
- 11
- 主要终点
- Incidence of DLTs, Dose escalation phase, Module 2
研究概览
简要总结
In the Dose Escalation Phase:
- To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in separate combinations with cemiplimab or ubamatamab, to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) for these combinations
In the Dose Expansion Phase:
- Module 1: To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or cemiplimab + fianlimab (as of PA6) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Module 2: To assess the preliminary efficacy of REGN5668 in combination with ubamatamab, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 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
- •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
- •Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1 as described in the protocol.
- •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
- •Note: Other protocol-defined inclusion criteria apply
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 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 Exclusion criteria apply
- •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 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
结局指标
主要结局
Incidence of DLTs, Dose escalation phase, Module 2
Incidence of DLTs, Dose escalation phase, Module 2
Incidence of dose limiting toxicities (DLT), Dose escalation phase, Module 1
Incidence of dose limiting toxicities (DLT), Dose escalation phase, Module 1
Incidence of treatment-emergent adverse events (TEAEs), Primary: Dose escalation phase, Secondary: Dose expansion phase
Incidence of treatment-emergent adverse events (TEAEs), Primary: Dose escalation phase, Secondary: Dose expansion phase
Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or ubamatamab, Primary: Dose escalation phase
Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or ubamatamab, Primary: Dose escalation phase
ORR defined by RECIST 1.1 (Eisenhauer, 2009) of REGN5668 in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination), Primary: Dose expansion phase
ORR defined by RECIST 1.1 (Eisenhauer, 2009) of REGN5668 in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination), Primary: Dose expansion phase
Incidence of serious adverse events (SAEs), Primary: Dose escalation phase; Secondary: Dose expansion phase
Incidence of serious adverse events (SAEs), Primary: Dose escalation phase; Secondary: Dose expansion phase
Incidence of deaths, Primary: Dose escalation phase; Secondary: Dose expansion phase
Incidence of deaths, 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]), 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]), Primary: Dose escalation phase; Secondary: Dose expansion phase
次要结局
- ORR based on RECIST 1.1, Dose escalation phase
- Best Overall Response (BOR) based on RECIST 1.1, Dose escalation and expansion phases
- Duration of Response (DOR) based on RECIST 1.1, Dose escalation and expansion phases
- Disease Control Rate (DCR) based on RECIST 1.1, Dose escalation and expansion phases
- Progression Free Survival (PFS) based on RECIST 1.1, Dose escalation and expansion phases
- CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination), Dose escalation and expansion phases
- Concentration of REGN5668 in serum over time when dosed alone and in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab, Dose escalation and expansion phases
- Presence or absence of anti-drug antibodies against REGN5668, Dose escalation and expansion phases
- Presence or absence of anti-drug antibodies against ubamatamab, Dose escalation and expansion phases
- Presence or absence of anti-drug antibodies against cemiplimab, Dose escalation and expansion phases
- Presence or absence of anti-drug antibodies against fianlimab, Dose escalation and expansion phases
研究者
Medical Affairs
Scientific
Regeneron Pharmaceuticals Inc.