Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer

Study of REGN4018 Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer

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

Primary Objectives In the Dose Escalation Phase: • To assess the safety and pharmacokinetics (PK) in order to determine a maximally tolerated dose (MTD) or recommended phase 2 dose (RP2D) of REGN4018 as monotherapy and in combination with cemiplimab. In the Dose Expansion Phase: • To assess the preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab, (separately by cohort) as determined by the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Secondary Objectives In the Dose Escalation Phase: • To assess the preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) 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 REGN4018 as monotherapy and in combination with cemiplimab. To assess the effects of REGN4018 as monotherapy and in combination with cemiplimab on patient-reported outcomes (PROs), including health-related quality of life (HRQoL), functioning, and symptoms In both the Dose Escalation and Dose Expansion Phases: To assess preliminary efficacy of REGN4018 as monotherapy and in combination with cemiplimab (separately by cohort) as measured by ORR based on iRECIST, best overall response (BOR), duration of response (DOR), disease control rate, complete response (CR) rate and progression-free survival (PFS) based on RECIST 1.1 and iRECIST To assess efficacy of REGN4018 as monotherapy and in combination with cemiplimab as measured by CA-125 level. Immunogenicity of REGN4018 and cemiplimab

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 during 6-week cycle (42 days).

Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (irAEs)) for REGN4018 monotherapy

Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for REGN4018 monotherapy

Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab

Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Eisenhauer 2009) for REGN4018 monotherapy

Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy

Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab

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."

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

Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 monotherapy

Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 with cemiplimab

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 MOST-T24 (MOST v2) (King et al. 2018) contains 24 of the original 35 items, focusing on symptoms (21 items) and well-being (3 items). 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). For all multi-item indexes, except the MOST-well-being index, compute the average of the component items (range 0-10) and then multiply this score by 10 (0-100 range). Thus, a higher score is equal to higher symptom burden. To calculate the MOST-Well-being index, repeat these same steps (i.e. take the average of the component items and multiply this score by 10) and then subtract this score from 100 so that a higher score is equal to greater well-being.

Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for REGN4018 with cemiplimab

Key Inclusion Criteria: 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 ≥2x 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 Adequate organ and bone marrow function as defined in the protocol Life expectancy of at least 3 months Randomized phase 2 expansion cohorts only: Platinum resistant ovarian cancer patients who have had 1 to 4 lines of platinum-based therapy and prior treatment with a poly ADP-ribose polymerase (PARP) inhibitor or bevacizumab as defined in the protocol. Key Exclusion Criteria: Recent treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy Expansion cohort only: More than 4 prior lines of cytotoxic chemotherapy Prior treatment with a Mucin 16 (MUC16)-targeted therapy Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression 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