A Study to Find Out How Safe REGN5668 is and How Well it Works In Adult Women When Given With Either Cemiplimab, or Cemiplimab + Fianlimab, or Ubamatamab
- Conditions
- Ovarian CancerFallopian Tube CancerPrimary Peritoneal CancerEndometrial Cancer
- Interventions
- Drug: Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)]
- Registration Number
- NCT04590326
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 612
- 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 1.
- 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
Key
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Module 1 REGN5668 REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab Module 1 Cemiplimab REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab Module 1 Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)] REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab Module 2 REGN5668 REGN5668 and ubamatamab Module 2 Ubamatamab REGN5668 and ubamatamab Module 2 Sarilumab REGN5668 and ubamatamab
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities (DLT) 42 days Dose escalation phase, Module 1
Incidence of DLTs 21 days post combination administration Dose escalation phase, Module 2
Incidence of Treatment-Emergent Adverse Events (TEAEs) Through study completion, up to 5 years Primary: Dose escalation phase Secondary: Dose expansion phase
Incidence of Serious Adverse Events (SAEs) Through study completion, up to 5 years Primary: Dose escalation phase Secondary: Dose expansion phase
Incidence of deaths 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]) 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 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) Through study completion, up to 5 years Primary: Dose expansion phase
- Secondary Outcome Measures
Name Time Method ORR based on RECIST 1.1 Through study completion, up to 5 years Dose escalation phase
Best Overall Response (BOR) based on RECIST 1.1 Through study completion, up to 5 years Dose escalation and expansion phases
Duration Of Response (DOR) based on RECIST 1.1 Through study completion, up to 5 years Dose escalation and expansion phases
Disease Control Rate (DCR) based on RECIST 1.1 Through study completion, up to 5 years Dose escalation and expansion phases
Progression-Free Survival (PFS) based on RECIST 1.1 Through study completion, up to 5 years Dose escalation and expansion phases
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 Dose escalation and expansion phases
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 Dose escalation and expansion phases
Presence or absence of anti-drug antibodies against REGN5668 Through study completion, up to 5 years Dose escalation and expansion phases
Presence or absence of anti-drug antibodies against ubamatamab Through study completion, up to 5 years Dose escalation and expansion phases
Presence or absence of anti-drug antibodies against cemiplimab Through study completion, up to 5 years Dose escalation and expansion phases
Presence or absence of anti-drug antibodies against fianlimab Through study completion, up to 5 years Dose escalation and expansion phases
Trial Locations
- Locations (24)
Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
The City of Hope Orange County Lennar Foundation Cancer Center
🇺🇸Irvine, California, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute Brookline Avenue
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Scroll for more (14 remaining)Chao Family Comprehensive Cancer Center🇺🇸Orange, California, United States