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

A Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific Antibody) Administered in Combination With Other Agents in MUC16 + Malignancies

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 Overview

• Status: Recruiting
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Endometrial Cancer; Primary Peritoneal Cancer
• Intervention / Treatment: Drug: REGN5668; Drug: Cemiplimab; Drug: Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)]; Drug: Ubamatamab; Drug: Sarilumab

• Study Type: Interventional
• Enrollment (Estimated): 612
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • Universitair Ziekenhuis Leuven
• France
  • Villejuif, France, 94805
    • Recruiting
    • Institut Gustave Roussy
  • Auvergne-Rhône
    • Pierre-Bénite, Auvergne-Rhône, France, 69310
      • Recruiting
      • Hôpital Lyon Sud
  • Bourgogne-Franche-Comté
    • Dijon, Bourgogne-Franche-Comté, France, 21000
      • Recruiting
      • Centre Georges Francois Leclerc
  • Normandy
    • Caen, Normandy, France, 14076
      • Recruiting
      • Centre Francois Baclesse (CFB)
  • Nouvelle-Aquitaine
    • Bordeaux, Nouvelle-Aquitaine, France, 33076
      • Recruiting
      • Institut Bergonie
• Spain
  • Girona, Spain, 17007
    • Recruiting
    • Institut Catala dOncologia Girona
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundación Jiménez
  • Madrid, Spain, 28040
    • Recruiting
    • Ciudad Universitaria
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre Universidad Complutense de Madrid UCM
  • A Coruna
    • Santiago de Compostela, A Coruna, Spain, 15706
      • Recruiting
      • Hospital Clinico Universitario Santiago de Compostela
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Comprehensive Cancer Center
    • Irvine, California, United States, 92618
      • Recruiting
      • The City of Hope Orange County Lennar Foundation Cancer Center
    • Orange, California, United States, 92868
      • Recruiting
      • Chao Family Comprehensive Cancer Center
  • Florida
    • Tampa, Florida, United States, 33612
      • Completed
      • H. Lee Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute Brookline Avenue
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Perelman School of Medicine at the University of Pennsylvania
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Seattle Cancer Care Alliance at South Lake Union - G3630

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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
2. Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1 as described in the protocol.
3. Has a serum CA-125 level ≥2x ULN (in screening, not applicable to endometrial cohorts)
4. Has adequate organ and bone marrow function as defined in the protocol
5. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Has a life expectancy of at least 3 months
7. 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 Exclusion Criteria:

1. Current or recent (as defined in the protocol) treatment with an investigational agent, systemic biologic therapy, or anti-cancer immunotherapy
2. 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
3. Prior treatment with a Mucin 16 (MUC16)-targeted therapy
4. Ovarian Expansion cohorts only: More than 5 prior lines of systemic therapy
5. 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
6. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol
7. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
8. Has history of clinically significant cardiovascular disease as defined in the protocol
9. Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s).

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1; REGN5668 in combination with cemiplimab, or cemiplimab + fianlimab	Drug: REGN5668; Administer per the protocol; Drug: Cemiplimab; Administer per the protocol; Other Names: REGN2810; Libtayo®; Drug: Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)]; Administer per the protocol
Experimental: Module 2; REGN5668 and ubamatamab	Drug: REGN5668; Administer per the protocol; Drug: Ubamatamab; Administer per the protocol; Other Names: REGN4018; Drug: Sarilumab; Administer per the protocol; Other Names: Kevzara®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of DLTs	Dose escalation phase, Module 2	21 days post combination administration
Incidence of deaths	Primary: Dose escalation phase Secondary: Dose expansion phase	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	Through study completion, up to 5 years
Incidence of Dose Limiting Toxicities (DLT)	Dose escalation phase, Module 1	42 days
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Primary: Dose escalation phase Secondary: Dose expansion phase	Through study completion, up to 5 years
Incidence of Serious Adverse Events (SAEs)	Primary: Dose escalation phase Secondary: Dose expansion phase	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	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	Through study completion, up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or absence of anti-drug antibodies against REGN5668	Dose escalation and expansion phases	Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against cemiplimab	Dose escalation and expansion phases	Through study completion, up to 5 years
ORR based on RECIST 1.1	Dose escalation phase	Through study completion, up to 5 years
Best Overall Response (BOR) based on RECIST 1.1	Dose escalation and expansion phases	Through study completion, up to 5 years
Duration Of Response (DOR) based on RECIST 1.1	Dose escalation and expansion phases	Through study completion, up to 5 years
Disease Control Rate (DCR) based on RECIST 1.1	Dose escalation and expansion phases	Through study completion, up to 5 years
Progression-Free Survival (PFS) based on RECIST 1.1	Dose escalation and expansion phases	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	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	Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against ubamatamab	Dose escalation and expansion phases	Through study completion, up to 5 years
Presence or absence of anti-drug antibodies against fianlimab	Dose escalation and expansion phases	Through study completion, up to 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2020
• Primary Completion (Estimated): March 25, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: October 9, 2020
• First Submitted That Met QC Criteria: October 9, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Refractory; Progressive; Recurrent; Serum CA-125 levels >= 2x ULN
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Uterine Neoplasms; Fallopian Tube Diseases; Pathological Conditions, Signs and Symptoms; Recurrence; Ovarian Neoplasms; Endometrial Neoplasms; Fallopian Tube Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab; sarilumab
• Other Study ID Numbers: R5668-ONC-1938; 2022-501904-83-00 (Ctis: EUCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No