A Study to Find Out How Safe REGN5668 is and How Well it Works In Adult Women When Given With Either Cemiplimab, or Cemiplimab + Fianlimab, or Ubamatamab

Official title

A Phase 1/2 Study of REGN5668 (MUC16xCD28, a Costimulatory Bispecific Antibody) Administered in Combination With Other Agents in MUC16 + Malignancies

Overview

This study is researching an investigational drug called REGN5668 : * alone or, * combined with cemiplimab (also known as REGN2810) or, * combined with both cemiplimab and fianlimab (also known as REGN3767), or * combined with ubamatamab (also known as 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) is 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, cemiplimab and fianlimab, or ubamatamab * How REGN5668 works in the body either alone and/or in combination with cemiplimab, cemiplimab and fianlimab, or ubamatamab * How much of the study drugs (REGN5668, cemiplimab, fianlimab, ubamatamab) are in the blood * To see if REGN5668 in combination with cemiplimab, cemiplimab and fianlimab, or ubamatamab works to treat cancer

Interventions

• Drug REGN5668
  Administer per the protocol
• Drug Cemiplimab
  Administer per the protocol
• Drug Ubamatamab
  Administer per the protocol
• Drug Sarilumab
  Administer per the protocol
• Drug Cemiplimab + Fianlimab [Fixed Dose Combination (FDC)]
  Administer per the protocol

Primary outcome measures

• Incidence of Dose Limiting Toxicities (DLT) [Time frame: 42 days]
• Incidence of DLTs [Time frame: 21 days post combination administration]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Through study completion, up to 5 years]
• Incidence of Serious Adverse Events (SAEs) [Time frame: Through study completion, up to 5 years]
• Incidence of deaths [Time frame: 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]) [Time frame: Through study completion, up to 5 years]
• Concentrations of REGN5668 in serum when dosed alone and in combination with cemiplimab or ubamatamab [Time frame: Through study completion, up to 5 years]
• Objective Response Rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Eisenhauer, 2009) of REGN5668 in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination) [Time frame: Through study completion, up to 5 years]

Secondary outcome measures (11)

• ORR based on RECIST 1.1 [Time frame: Through study completion, up to 5 years]
• Best Overall Response (BOR) based on RECIST 1.1 [Time frame: Through study completion, up to 5 years]
• Duration Of Response (DOR) based on RECIST 1.1 [Time frame: Through study completion, up to 5 years]
• Disease Control Rate (DCR) based on RECIST 1.1 [Time frame: Through study completion, up to 5 years]
• Progression-Free Survival (PFS) based on RECIST 1.1 [Time frame: Through study completion, up to 5 years]
• Cancer Antigen 125 (CA-125) change from baseline after treatment with REGN5668 in combinations with cemiplimab, cemiplimab + fianlimab, or ubamatamab (separately by cohort and combination) [Time frame: Through study completion, up to 5 years]
• Concentration of REGN5668 in serum over time when dosed alone and in combination with cemiplimab, cemiplimab + fianlimab, or ubamatamab [Time frame: Through study completion, up to 5 years]
• Presence or absence of anti-drug antibodies against REGN5668 [Time frame: Through study completion, up to 5 years]
• Presence or absence of anti-drug antibodies against ubamatamab [Time frame: Through study completion, up to 5 years]
• Presence or absence of anti-drug antibodies against cemiplimab [Time frame: Through study completion, up to 5 years]
• Presence or absence of anti-drug antibodies against fianlimab [Time frame: Through study completion, up to 5 years]

Eligibility criteria

Inclusion criteria

• 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
• Expansion cohorts only: Has at least 1 lesion that is measurable by RECIST 1.1 as described in the protocol.
• Has a serum CA-125 level ≥2x ULN (in screening, not applicable to endometrial cohorts)
• 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
• 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

Exclusion criteria

• Current or recent (as defined in the protocol) treatment with an investigational agent, systemic biologic therapy, or anti-cancer immunotherapy
• 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 Mucin 16 (MUC16)-targeted therapy
• Ovarian Expansion cohorts only: More than 5 prior lines of systemic therapy
• 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
• Has known allergy or hypersensitivity to cemiplimab and/or components of study drug(s).

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 13 centers

• City of Hope Comprehensive Cancer Center — Duarte
• The City of Hope Orange County Lennar Foundation Cancer Center — Irvine
• Chao Family Comprehensive Cancer Center — Orange
• H. Lee Moffitt Cancer Center — Tampa
• Robert H. Lurie Comprehensive Cancer Center of Northwestern University — Chicago
• University of Chicago Medical Center — Chicago
• Massachusetts General Hospital — Boston
• Dana Farber Cancer Institute Brookline Avenue — Boston
• … and 5 more centers

France · 5 centers

• Hopital Lyon Sud — Pierre-Bénite
• Centre Georges Francois Leclerc — Dijon
• Institut Bergonie — Bordeaux
• Centre Francois Baclesse (CFB) — Caen
• Institut Gustave Roussy — Villejuif

Spain · 5 centers

• Hospital Clinico Universitario Santiago de Compostela — Santiago de Compostela
• Institut Catala dOncologia Girona — Girona
• Ciudad Universitaria — Madrid
• Hospital Universitario Fundacion Jimenez — Madrid
• Hospital Universitario 12 de Octubre Universidad Complutense de Madrid UCM — Madrid

Belgium · 1 center

• Universitair Ziekenhuis Leuven — Leuven

Identifiers

NCT: NCT04590326 · R5668-ONC-1938 · 2022-501904-83-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗