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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
612
Administer per the protocol
Administer per the protocol
Administer per the protocol
Administer per the protocol
Administer per the protocol
City of Hope Comprehensive Cancer Center
Duarte, California, United States
RECRUITINGThe City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California, United States
RECRUITINGChao Family Comprehensive Cancer Center
Orange, California, United States
RECRUITINGH. Lee Moffitt Cancer Center
Tampa, Florida, United States
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
ORR based on RECIST 1.1
Dose escalation phase
Time frame: Through study completion, up to 5 years
Best Overall Response (BOR) based on RECIST 1.1
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years
Duration Of Response (DOR) based on RECIST 1.1
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years
Disease Control Rate (DCR) based on RECIST 1.1
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years
Progression-Free Survival (PFS) based on RECIST 1.1
Dose escalation and expansion phases
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)
Dose escalation and expansion phases
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
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against REGN5668
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against ubamatamab
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Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States
RECRUITINGUniversity of Chicago Medical Center
Chicago, Illinois, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGDana Farber Cancer Institute Brookline Avenue
Boston, Massachusetts, United States
RECRUITINGKarmanos Cancer Institute
Detroit, Michigan, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITING...and 14 more locations
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against cemiplimab
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against fianlimab
Dose escalation and expansion phases
Time frame: Through study completion, up to 5 years