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

Study Overview
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Brief Summary
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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

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

Conditions
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Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Cancer

Intervention / Treatment
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* Drug: REGN5668
* Drug: Cemiplimab
* Drug: REGN4018


Participation Criteria
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Eligibility Criteria
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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 Has a serum CA-125 level ≥2x ULN (in screening) 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 Key Exclusion Criteria: 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 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 history of clinically significant cardiovascular disease as defined in the protocol Note: Other protocol-defined Inclusion/Exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Module 1<br>REGN5668 and cemiplimab | Drug: REGN5668<br>* REGN5668 will be administered by once weekly intravenous (IV) infusion.<br>Drug: Cemiplimab<br>* 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.<br>* Other names: Libtayo;|
| Experimental: Module 2<br>REGN5668 and REGN4018 | Drug: REGN5668<br>* REGN5668 will be administered by once weekly intravenous (IV) infusion.<br>Drug: REGN4018<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLT) | Dose escalation phase, Module 1 | 42 days | 
| Incidence of DLTs | Dose escalation phase, Module 2 | 21 days post combination administration | 
| 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 | 
| 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 | 
| Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or REGN4018 | Primary: Dose escalation phase Secondary: Dose expansion phase | Up to 62 weeks | 
| ORR defined by RECIST 1.1 (Eisenhauer, 2009) in combination with cemiplimab or REGN4018 (separately by cohort and combination) | Primary: Dose expansion phase Secondary: Dose escalation phase | Up to 62 weeks | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Progressive, Recurrent, Refractory, Serum CA-125 levels >= 2x ULN