Study of REGN5668 Administered in Combination With Cemiplimab or REGN4018 in Adult Women With Recurrent Ovarian Cancer

Sponsor

Regeneron Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04590326

Collaborator

(none)

326

Enrollment

Locations

Arms

67.6

Anticipated Duration (Months)

46.6

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objectives of the study are:

In the Dose Escalation Phase:

To assess the safety, tolerability, and pharmacokinetics (PK) of REGN5668 alone and in separate combinations with cemiplimab or REGN4018, in order to determine a maximally tolerated dose(s) (MTD) or recommended phase 2 dose(s) (RP2D) of these combinations

In the Dose Expansion Phase:

To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018, (separately by cohort and combination) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

The secondary objectives of the study are:

In the Dose Escalation Phase:

To assess the preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as determined by ORR by RECIST 1.1

In the Dose Expansion Phase:

To characterize the safety profile in each expansion cohort
To characterize the PK of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination)

In both the Dose Escalation and Dose Expansion Phases:

To assess preliminary efficacy of REGN5668 in combination with cemiplimab or REGN4018 (separately by cohort and combination) as measured by ORR based on immune based therapy RECIST (iRECIST), best overall response (BOR), duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) based on RECIST 1.1 and iRECIST
To assess changes in CA-125 levels from baseline after treatment with REGN5668 in combinations with cemiplimab or REGN4018 (separately by cohort and combination)
Immunogenicity of REGN5668, alone and in combinations with cemiplimab or REGN4018

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer	Drug: REGN5668 Drug: Cemiplimab Drug: REGN4018	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

326 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 :

Dec 9, 2020

Anticipated Primary Completion Date :

Jul 28, 2026

Anticipated Study Completion Date :

Jul 28, 2026

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-week monotherapy lead-in of REGN4018 will be administered by once weekly IV infusion. After lead-in, REGN5668 and REGN4018 will be administered concomitantly.

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-week monotherapy lead-in of REGN4018 will be administered by once weekly IV infusion. After lead-in, REGN5668 and REGN4018 will be administered concomitantly.

Outcome Measures

Primary Outcome Measures

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
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 [Up to 62 weeks]
Primary: Dose escalation phase Secondary: Dose expansion phase
ORR defined by RECIST 1.1 (Eisenhauer, 2009) in combination with cemiplimab or REGN4018 (separately by cohort and combination) [Up to 62 weeks]
Primary: Dose expansion phase Secondary: Dose escalation phase

Secondary Outcome Measures

Concentration of REGN4018 in serum over time [Up to 62 weeks]
Dose expansion phase
Concentration of cemiplimab in serum over time [Up to 62 weeks]
Dose expansion phase
ORR based on iRECIST [Up to 62 weeks]
Dose escalation and expansion phases
BOR based on RECIST 1.1 and iRECIST [Up to 62 weeks]
Dose escalation and expansion phases
DOR based on RECIST 1.1 and iRECIST [Up to 62 weeks]
Dose escalation and expansion phases
DCR based on RECIST 1.1 and iRECIST [Up to 62 weeks]
Dose escalation and expansion phases
PFS based on RECIST 1.1 and iRECIST [Up to 62 weeks]
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) [Up to 62 weeks]
Dose escalation and expansion phases
Presence or absence of anti-drug antibodies against REGN5668 [Up to 62 weeks]
Dose escalation and expansion phases
Presence or absence of anti-drug antibodies against REGN4018 [Up to 62 weeks]
Dose escalation and expansion phases
Presence or absence of anti-drug antibodies against cemiplimab [Up to 62 weeks]
Dose escalation and expansion phases

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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
In dose escalation, patients will provide either newly obtained biopsy (newly obtained biopsies at screening are required unless medically inappropriate and discussed with medical monitor. If fresh biopsies are not appropriate, and after sponsor approval, archival tumor tissue in dose escalation is acceptable. In dose expansion, patients will provide a fresh tumor biopsy in screening and on treatment. Hence, in expansion cohorts, only patients who (in the opinion of the investigator) have accessible lesions that can be biopsied without significant risk to the patient are eligible.
Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation.
Has a serum CA-125 level ≥2x ULN (in screening)
Has adequate organ and bone marrow function as defined in the protocol
Has a life expectancy of at least 3 months

Key Exclusion Criteria:

Has participated in a study of an investigational agent (except biologics and/or immunotherapy) or an investigational device within 4 weeks of first dose of study drug
Has received treatment with an approved systemic therapy (except biologics and/or immunotherapy) within 3 weeks or has not yet recovered as defined in the protocol
Prior anti-cancer immunotherapy as defined in the protocol
Has received radiation therapy or major surgery within 14 days of first administration of study drug as defined in the protocol
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 3 prior lines of cytotoxic chemotherapy for platinum-experienced and/or intolerant disease
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 encephalitis, meningitis, organic brain disease (eg, Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study drug
Has history of clinically significant cardiovascular disease as defined in the protocol

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
2	Northwestern Memorial Hospital	Chicago	Illinois	United States	60611
3	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	The Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210