A Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific Antibody) Administered in Combination With Other Agents in MUC16 + Malignancies
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
Arms & interventions
- DrugREGN5668
Administer per the protocol
- DrugCemiplimab
Administer per the protocol
- DrugUbamatamab
Administer per the protocol
- DrugSarilumab
Administer per the protocol
- DrugCemiplimab + Fianlimab [Fixed Dose Combination (FDC)]
Administer per the protocol
Outcome measures
Primary
Incidence of Dose Limiting Toxicities (DLT)
Dose escalation phase, Module 1
Time frame: 42 days
Incidence of DLTs
Dose escalation phase, Module 2
Time frame: 21 days post combination administration
Incidence of Treatment-Emergent Adverse Events (TEAEs)
Primary: Dose escalation phase Secondary: Dose expansion phase
Time frame: Through study completion, up to 5 years
Incidence of Serious Adverse Events (SAEs)
Primary: Dose escalation phase Secondary: Dose expansion phase
Time frame: Through study completion, up to 5 years
Incidence of deaths
Primary: Dose escalation phase Secondary: Dose expansion phase
Time frame: Through study completion, up to 5 years
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
Time frame: Through study completion, up to 5 years
Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or ubamatamab
Primary: Dose escalation phase
Time frame: Through study completion, up to 5 years
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)
Primary: Dose expansion phase
Time frame: Through study completion, up to 5 years
Secondary
ORR based on RECIST 1.1
Time frame: Through study completion, up to 5 years
Best Overall Response (BOR) based on RECIST 1.1
Time frame: Through study completion, up to 5 years
Duration Of Response (DOR) based on RECIST 1.1
Time frame: Through study completion, up to 5 years
Disease Control Rate (DCR) based on RECIST 1.1
Time frame: Through study completion, up to 5 years
Progression-Free Survival (PFS) based on RECIST 1.1
Time frame: 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)
Time frame: 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
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against REGN5668
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against ubamatamab
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against cemiplimab
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against fianlimab
Time frame: Through study completion, up to 5 years
Eligibility criteria
Study locations (13)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
The City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California, 92618
Chao Family Comprehensive Cancer Center
Orange, California, 92868
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, 60611
University of Chicago Medical Center
Chicago, Illinois, 60637
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute Brookline Avenue
Boston, Massachusetts, 02215
Karmanos Cancer Institute
Detroit, Michigan, 48201
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Seattle Cancer Care Alliance at South Lake Union - G3630
Seattle, Washington, 98109