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

Ovarian Cancer Clinical Trial

Official title:

Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific) Administered in Combination With Cemiplimab or REGN4018 (MUC16xCD3)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04590326
• Other study ID #: R5668-ONC-1938
• Secondary ID: 2022-501904-83-0
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 9, 2020
• Est. completion date: April 27, 2027

Study information

• Verified date: March 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 612
• Est. completion date: April 27, 2027
• Est. primary completion date: April 27, 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Primary Peritoneal Cancer

Intervention

Drug:
• REGN5668
REGN5668 will be administered by once weekly intravenous (IV) infusion.
• 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.
• 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.
• Sarilumab
Administered by IV infusion as prophylaxis for mitigating potential CRS in patients receiving REGN4018

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Leuven	Leuven	Vlaams-Brabant
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicities (DLT)	Dose escalation phase, Module 1	42 days
Primary	Incidence of DLTs	Dose escalation phase, Module 2	21 days post combination administration
Primary	Incidence of treatment-emergent adverse events (TEAEs)	Primary: Dose escalation phase Secondary: Dose expansion phase	Through study completion, up to 5 years
Primary	Incidence of serious adverse events (SAEs)	Primary: Dose escalation phase Secondary: Dose expansion phase	Through study completion, up to 5 years
Primary	Incidence of deaths	Primary: Dose escalation phase Secondary: Dose expansion phase	Through study completion, up to 5 years
Primary	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
Primary	Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or REGN4018	Primary: Dose escalation phase Secondary: Dose expansion phase	Through study completion, up to 5 years
Primary	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)	Primary: Dose expansion phase Secondary: Dose escalation phase	Through study completion, up to 5 years
Secondary	Concentration of REGN4018 in serum over time	Dose expansion phase	Through study completion, up to 5 years
Secondary	Concentration of cemiplimab in serum over time	Dose expansion phase	Through study completion, up to 5 years
Secondary	ORR based on Immune-based therapy RECIST (iRECIST)	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	BOR based on RECIST 1.1 and iRECIST	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	DOR based on RECIST 1.1 and iRECIST	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	DCR based on RECIST 1.1 and iRECIST	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	PFS based on RECIST 1.1 and iRECIST	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	CA-125 change from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination)	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	Presence or absence of anti-drug antibodies against REGN5668	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	Presence or absence of anti-drug antibodies against REGN4018	Dose escalation and expansion phases	Through study completion, up to 5 years
Secondary	Presence or absence of anti-drug antibodies against cemiplimab	Dose escalation and expansion phases	Through study completion, up to 5 years