Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer or Other Recurrent Mucin-16 Expressing (MUC16+) Cancers

Study Overview
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Brief Summary
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The main purpose of this study is to: Learn about the safety of REGN4018 and to find out what dose of REGN4018 can be given alone or with cemiplimab to patients with ovarian cancer or cancer of the uterus The study will also look at the levels of REGN4018 and/or cemiplimab in your body and measure how well your body can remove the study drug(s). This is called pharmacokinetics The study will also look at any signs that REGN4018 alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus To find out how safe and tolerable the sarilumab pretreatment is, in combination with REGN4018 and cemiplimab

Official Title
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A Phase 1/2 Study of REGN4018 (A MUC16xCD3 Bispecific Antibody) Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer or Other Recurrent MUC16+ Cancers

Conditions
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Recurrent Ovarian Cancer, Recurrent Fallopian Tube Cancer, Recurrent Primary Peritoneal Cancer, Recurrent Endometrial Cancer

Intervention / Treatment
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* Drug: REGN4018
* Drug: cemiplimab
* Drug: Sarilumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Ovarian Cancer Cohorts Only: Patients with histologically or cytologically confirmed diagnosis of advanced, epithelial ovarian cancer (except carcinosarcoma), primary peritoneal, or fallopian tube cancer who have all of the following: serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening) has received at least 1 line of platinum-containing therapy or must be platinum-intolerant (applicable for dose escalation and non-randomized dose expansion cohorts) documented relapse or progression on or after the most recent line of therapy no standard therapy options likely to convey clinical benefit Adequate organ and bone marrow function as defined in the protocol Life expectancy of at least 3 months Randomized phase 2 expansion cohort (Ovarian Cancer only): Platinum-resistant ovarian cancer patients who have had 1 to 3 lines of platinum-based therapy as defined in the protocol. Endometrial Cancer Cohorts Only: histologically confirmed endometrial cancer that has progressed or recurrent after prior anti-Programmed Cell Death Ligand 1 (PD-1) therapy and platinum-based chemotherapy: MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC) 1-2 prior lines of systemic therapy Key Exclusion Criteria: Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy Prior treatment with a MUC16 - targeted therapy Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol History and/or current cardiac findings as defined in the protocol Severe and/or uncontrolled hypertension at screening. Patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen Note: Other protocol 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: Monotherapy<br>REGN4018 administration | Drug: REGN4018<br>* REGN4018 will be administered in a series of dose escalation and dose expansion cohorts by intravenous (IV) infusion and/or subcutaneous (SC) as described in the protocol.<br>* Other names: Ubamatamab®;Drug: Sarilumab<br>* Sarilumab will be administered by IV, one-time-only, prior to IV/SC REGN4018.<br>|
| Experimental: Combination Therapy<br>REGN4018 and cemiplimab administration | Drug: REGN4018<br>* REGN4018 will be administered in a series of dose escalation and dose expansion cohorts by intravenous (IV) infusion and/or subcutaneous (SC) as described in the protocol.<br>* Other names: Ubamatamab®;Drug: cemiplimab<br>* Cemiplimab will be administered by IV infusion after REGN4018 monotherapy lead-in phase.<br>* Other names: REGN2810;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy | Dose Escalation Phase | From Cycle 1, Day 1 up to 35 days | 
| Number of participants with DLTs for REGN4018 with cemiplimab | Dose Escalation Phase | From Cycle 2, Day 1 up to 21 days | 
| Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for REGN4018 monotherapy | Dose Escalation Phase | Up to 62 weeks | 
| Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab | Dose Escalation Phase | Up to 62 weeks | 
| Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy | Dose Escalation Phase | Up to 62 weeks | 
| Number of participants with SAEs for REGN4018 with cemiplimab | Dose Escalation Phase | Up to 62 weeks | 
| Number of deaths for REGN4018 monotherapy | Dose Escalation Phase | Up to 62 weeks | 
| Number of deaths for REGN4018 with cemiplimab | Dose Escalation Phase | Up to 62 weeks | 
| Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for REGN4018 monotherapy | Dose Escalation Phase | Up to 62 weeks | 
| Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab | Dose Escalation Phase | Up to 62 weeks | 
| Concentration of REGN4018 in serum over time for REGN4018 monotherapy | Dose Escalation Phase | Up to 62 weeks | 
| Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab | Dose Escalation Phase | Up to 62 weeks | 
| Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| ORR defined by RECIST 1.1 for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR based on RECIST 1.1 for REGN4018 monotherapy | Dose Escalation Phase | Up to 62 weeks | 
| ORR based on RECIST 1.1 for REGN4018 with cemiplimab | Dose Escalation Phase | Up to 62 weeks | 
| Number of participants with TEAEs (including imAEs) for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Number of participants with SAEs for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Number of participants with SAEs for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Number of deaths for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Number of deaths for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Concentration of REGN4018 in serum over time for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Change from baseline in quality of life (QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 GHS/QoL score for REGN4018 monotherapy | Dose Expansion Phase The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social) , symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as not at all and 4 as very much. | Baseline up to 62 weeks | 
| Change from baseline in quality of life (QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 GHS/QoL score for REGN4018 with cemiplimab | Dose Expansion Phase | Baseline up to 62 weeks | 
| Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 monotherapy | Dose Expansion Phase | Baseline up to 62 weeks | 
| Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 with cemiplimab | Dose Expansion Phase | Baseline up to 62 weeks | 
| Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for REGN4018 monotherapy | Dose Expansion Phase excluding the Endometrial Cancer Cohort The MOST-24 is a 24-item questionnaire used to measure the impact of chemotherapy on symptoms (21 items) and well-being (3 items). The expected questionnaire completion time is less than 5 minutes. The prevalence of each MOST item at assessment time points can be summarized by providing the mean, standard deviation and proportions based on the MOST response format, a numeric rating scale with integers from zero to 10, with five verbal anchors: 'No trouble at all' (0), 'Mild' (1-3), 'Moderate' (4-6), 'Severe' (7-10), and 'Worst I can imagine' (10). | Baseline up to 62 weeks | 
| Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for REGN4018 with cemiplimab | Dose Expansion Phase Not applicable to Endometrial Cancer Cohort | Baseline up to 62 weeks | 
| Time to deterioration in GHS/QoL for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Time to deterioration in GHS/QoL for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Time to deterioration in physical functioning for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Time to deterioration in physical functioning for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Time to deterioration in abdominal symptoms for REGN4018 monotherapy | Dose Expansion Phase | Up to 62 weeks | 
| Time to deterioration in abdominal symptoms for REGN4018 with cemiplimab | Dose Expansion Phase | Up to 62 weeks | 
| Change from baseline in QoL as measured by EQ-5D for REGN4018 monotherapy | Dose Expansion Phase | Baseline up to 62 weeks | 
| Change from baseline in QoL as measured by EQ-5D for REGN4018 with cemiplimab | Dose Expansion Phase | Baseline up to 62 weeks | 
| ORR based on iRECIST for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| ORR based on iRECIST for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| BOR based on iRECIST for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| BOR based on RECIST 1.1 for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| BOR based on iRECIST for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| DOR based on iRECIST for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| DOR based on RECIST 1.1 for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| DOR based on iRECIST for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Disease control rate based on RECIST 1.1 for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Disease control rate based on iRECIST for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Disease control rate based on iRECIST for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| CR rate based on iRECIST 1.1 for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| CR rate based on RECIST 1.1 for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| PFS based on iRECIST for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| PFS based on RECIST 1.1 for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| PFS based on iRECIST for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Cancer antigen-125 (CA-125) response for REGN4018 monotherapy | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| CA-125 response for REGN4018 with cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Presence or absence of anti-drug antibodies against REGN4018 | Dose Escalation and Dose Expansion Phases | Up to 62 weeks | 
| Presence or absence of anti-drug antibodies against cemiplimab | Dose Escalation and Dose Expansion Phases | Up to 62 weeks |