A Trial to Find Out How Safe REGN5668 is and How Well it Works When Given With Either Cemiplimab or REGN4018
- Conditions
- Ovarian CancerFallopian Tube CancerPrimary Peritoneal CancerEndometrial Cancer
- Interventions
- Registration Number
- NCT04590326
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching an investigational drug called REGN5668. Participants will receive additional investigational drugs in combination with REGN5668. These additional drugs include cemiplimab or 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) 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 or REGN4018
* How REGN5668 works in the body either alone and/or in combination with cemiplimab or REGN4018
* How much of the study drugs (REGN5668, cemiplimab, REGN4018) are in the blood
* To see if REGN5668 in combination with cemiplimab or REGN4018 works to treat cancer
* To find out how safe, tolerable, and effective in mitigating Cytokine Release Syndrome (CRS) sarilumab pretreatment is when given before REGN4018
- 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
- Prior anti-cancer immunotherapy as defined in the protocol
- Recent treatment with anti-Programmed Cell Death (PD-1)/PDL-1 therapy
- 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
- Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (including antibody drug conjugates)
- 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 2 REGN5668 REGN5668 and REGN4018 Module 2 REGN4018 REGN5668 and REGN4018 Module 2 Sarilumab REGN5668 and REGN4018 Module 1 REGN5668 REGN5668 and cemiplimab Module 1 Cemiplimab REGN5668 and cemiplimab
- Primary Outcome Measures
Name Time Method 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 REGN4018 Through study completion, up to 5 years Primary: Dose escalation phase Secondary: Dose expansion phase
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
ORR defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Eisenhauer, 2009) in combination with cemiplimab or REGN4018 (separately by cohort and combination) Through study completion, up to 5 years Primary: Dose expansion phase Secondary: Dose escalation phase
- Secondary Outcome Measures
Name Time Method BOR based on RECIST 1.1 and iRECIST Through study completion, up to 5 years Dose escalation and expansion phases
DOR based on RECIST 1.1 and iRECIST Through study completion, up to 5 years Dose escalation and expansion phases
Concentration of REGN4018 in serum over time Through study completion, up to 5 years Dose expansion phase
Concentration of cemiplimab in serum over time Through study completion, up to 5 years Dose expansion phase
ORR based on Immune-based therapy RECIST (iRECIST) Through study completion, up to 5 years Dose escalation and expansion phases
DCR based on RECIST 1.1 and iRECIST Through study completion, up to 5 years Dose escalation and expansion phases
PFS based on RECIST 1.1 and iRECIST Through study completion, up to 5 years Dose escalation and expansion phases
CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) 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 REGN4018 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
Trial Locations
- Locations (23)
Hopital Lyon Sud
🇫🇷Pierre-Benite, Lyon, France
Institut Gustave Roussy
🇫🇷Villejuif, France
The City of Hope Orange County Lennar Foundation Cancer Center
🇺🇸Irvine, California, United States
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
🇺🇸Chicago, Illinois, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Perelman School of Medicine at the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Centre Francois Baclesse (CFB)
🇫🇷Caen, Normandy, France
Institut Bergonie
🇫🇷Bordeaux, France
Hospital Clinico Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruna, Spain
Dana Farber Cancer Institute Brookline Avenue
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Seattle Cancer Care Alliance at South Lake Union - G3630
🇺🇸Seattle, Washington, United States
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Vlaams Brabant, Belgium
Centre Georges Francois Leclerc
🇫🇷Dijon, Bourgogne, France
Institut Catala dOncologia Girona
🇪🇸Girona, Spain
Ciudad Universitaria
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre Universidad Complutense de Madrid UCM
🇪🇸Madrid, Spain