A Trial to Find Out How Safe REGN5668 is and How Well it Works When Given With Either Cemiplimab or REGN4018

• ClinicalTrials.gov Identifier: NCT04590326
• Recruitment Status: Recruiting
• First Posted: October 19, 2020
• Last Update Posted: March 19, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

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

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Fallopian Tube Cancer; Primary Peritoneal Cancer; Endometrial Cancer	Drug: REGN5668; Drug: Cemiplimab; Drug: REGN4018; Drug: Sarilumab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 612 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3)
• Actual Study Start Date: December 9, 2020
• Estimated Primary Completion Date: April 27, 2027
• Estimated Study Completion Date: April 27, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Module 1; REGN5668 and cemiplimab	Drug: REGN5668; REGN5668 will be administered by once weekly intravenous (IV) infusion.; Drug: Cemiplimab; For Module 1, after a minimum of a 3-week monotherapy lead-in of REGN5668, cemiplimab will be administered concomitantly every 3 weeks (Q3W) by IV infusion.; Other Names: REGN2810; Libtayo
Experimental: Module 2; REGN5668 and REGN4018	Drug: REGN5668; REGN5668 will be administered by once weekly intravenous (IV) infusion.; Drug: REGN4018; For Module 2, a 4-5 week monotherapy lead-in of REGN4018 will be administered by once weekly IV infusion. After lead-in, REGN5668 and REGN4018 will be administered concomitantly.; Drug: Sarilumab; Administered by IV infusion as prophylaxis for mitigating potential CRS in patients receiving REGN4018

Outcome Measures

Primary Outcome Measures :

1. Incidence of dose limiting toxicities (DLT) [ Time Frame: 42 days ]
   Dose escalation phase, Module 1
2. Incidence of DLTs [ Time Frame: 21 days post combination administration ]
   Dose escalation phase, Module 2
3. Incidence of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, up to 5 years ]
   Primary: Dose escalation phase Secondary: Dose expansion phase
4. Incidence of serious adverse events (SAEs) [ Time Frame: Through study completion, up to 5 years ]
   Primary: Dose escalation phase Secondary: Dose expansion phase
5. Incidence of deaths [ Time Frame: Through study completion, up to 5 years ]
   Primary: Dose escalation phase Secondary: Dose expansion phase
6. 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]) [ Time Frame: Through study completion, up to 5 years ]
   Primary: Dose escalation phase Secondary: Dose expansion phase
7. Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or REGN4018 [ Time Frame: Through study completion, up to 5 years ]
   Primary: Dose escalation phase Secondary: Dose expansion phase
8. 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) [ Time Frame: Through study completion, up to 5 years ]
   Primary: Dose expansion phase Secondary: Dose escalation phase

Secondary Outcome Measures :

1. Concentration of REGN4018 in serum over time [ Time Frame: Through study completion, up to 5 years ]
   Dose expansion phase
2. Concentration of cemiplimab in serum over time [ Time Frame: Through study completion, up to 5 years ]
   Dose expansion phase
3. ORR based on Immune-based therapy RECIST (iRECIST) [ Time Frame: Through study completion, up to 5 years ]
   Dose escalation and expansion phases
4. BOR based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
   Dose escalation and expansion phases
5. DOR based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
   Dose escalation and expansion phases
6. DCR based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
   Dose escalation and expansion phases
7. PFS based on RECIST 1.1 and iRECIST [ Time Frame: Through study completion, up to 5 years ]
   Dose escalation and expansion phases
8. CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination) [ Time Frame: Through study completion, up to 5 years ]
   Dose escalation and expansion phases
9. Presence or absence of anti-drug antibodies against REGN5668 [ Time Frame: Through study completion, up to 5 years ]
   Dose escalation and expansion phases
10. Presence or absence of anti-drug antibodies against REGN4018 [ Time Frame: Through study completion, up to 5 years ]
    Dose escalation and expansion phases
11. Presence or absence of anti-drug antibodies against cemiplimab [ Time Frame: Through study completion, up to 5 years ]
    Dose escalation and expansion phases

Eligibility Criteria

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

Criteria

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. Prior anti-cancer immunotherapy as defined in the protocol
2. Recent treatment with anti-Programmed Cell Death (PD-1)/PDL-1 therapy
3. 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
4. Prior treatment with a MUC16-targeted therapy
5. Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (including antibody drug conjugates)
6. 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
7. Has ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments as defined in the protocol
8. Has untreated or active primary brain tumor, CNS metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
9. Has history of clinically significant cardiovascular disease as defined in the protocol
10. Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s).

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

United States, Florida

H. Lee Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 33612

United States, Illinois

Northwestern Memorial Hospital; Recruiting

Chicago, Illinois, United States, 60611

University of Chicago; Recruiting

Chicago, Illinois, United States, 60637

United States, Massachusetts

Massachusetts General Hospital Cancer Center; Recruiting

Boston, Massachusetts, United States, 02114

Dana Farber Cancer Institute; Recruiting

Boston, Massachusetts, United States, 02215

United States, Michigan

Karmanos Cancer Institute; Recruiting

Detroit, Michigan, United States, 48201

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

United States, Ohio

The Ohio State University Wexner Medical Center; Recruiting

Columbus, Ohio, United States, 43210

United States, Washington

Seattle Cancer Care Alliance; Recruiting

Seattle, Washington, United States, 98109

Belgium

Universitair Ziekenhuis Leuven; Recruiting

Leuven, Vlaams-Brabant, Belgium, 3000

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04590326
• Other Study ID Numbers: R5668-ONC-1938; 2022-501904-83-00 ( Other Identifier: EUCT Number )
• First Posted: October 19, 2020
• Last Update Posted: March 19, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• 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
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

Progressive; Recurrent; Refractory; Serum CA-125 levels >= 2x ULN

Additional relevant MeSH terms:

Endometrial Neoplasms; Fallopian Tube Neoplasms; Neoplasms by Site; Neoplasms; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Uterine Neoplasms; Uterine Diseases; Fallopian Tube Diseases; Cemiplimab; Antineoplastic Agents, Immunological; Antineoplastic Agents