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

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

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

Study Overview

• Status: Recruiting
• Conditions: Recurrent Endometrial Cancer; Recurrent Ovarian Cancer; Recurrent Fallopian Tube Cancer; Recurrent Primary Peritoneal Cancer
• Intervention / Treatment: Drug: REGN4018; Drug: Sarilumab; Drug: cemiplimab

• Study Type: Interventional
• Enrollment (Estimated): 690
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, NSW 2031
      • Recruiting
      • Prince of Wales Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Center
• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • Recruiting
      • Universitair Ziekenhuis Antwerpen
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6000
      • Recruiting
      • Grand Hôpital de Charleroi
  • Vlaams Brabant
    • Leuven, Vlaams Brabant, Belgium, 3000
      • Recruiting
      • UZLeuven
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Centre Regional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest - Institut Bergonie
  • Caen cedex 5, France, 14076
    • Recruiting
    • UNICANCER - Centre Francois Baclesse (CFB)
  • Villejuif Cedex, France, 94800
    • Recruiting
    • Institut Gustave Roussy
  • Bourgogne
    • Dijon cedex, Bourgogne, France, 21079
      • Recruiting
      • Centre Georges-Francois Leclerc
  • Cedex 2
    • Nice, Cedex 2, France, 06189
      • Recruiting
      • Centre Antoine Lacassagne
  • Lyon
    • Pierre-Benite, Lyon, France, 69310
      • Recruiting
      • Centre Hospitalier Lyon Sud, Hospices Civils de Lyon
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus RHCC - Rambam Medical Center
  • Tel Hashomer, Israel, 5265601
    • Recruiting
    • The Chaim Sheba Medical Center
• Italy
  • Milano, Italy, 20141
    • Recruiting
    • Istituto Europeo Di Oncologia
  • Naples, Italy, 80131
    • Recruiting
    • Instituto Nazionale Tumori- Fondazione Pascale
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Agostino Gemelli IRCCS di Roma
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 6351
    • Recruiting
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 08307
    • Recruiting
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Yonsei University Health System
  • Seoul, Korea, Republic of, 3080
    • Recruiting
    • Seoul National University College of Medicine
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • University Medical Center Groningen
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Recruiting
      • Radboudumc, dept Medical Oncology hp 452
  • Zuid Holland
    • Rotterdam, Zuid Holland, Netherlands, 3000 DR
      • Recruiting
      • Erasmus MC
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 8908
    • Recruiting
    • Institut Catala d'Oncologia
  • Barcelona, Spain, 08916
    • Recruiting
    • Institut Catala d'Oncologia
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario San Carlos
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Universitario Fundacion Jimenez Diaz
  • Santiago de Compostela, Spain, 15706
    • Recruiting
    • Hospital Clinico Universitatio Santiago de Compostela
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
  • Navarre
    • Madrid, Navarre, Spain, 28027
      • Recruiting
      • Clinica Universidad de Navarra
• United Kingdom
  • London, United Kingdom, W12 OHS
    • Recruiting
    • Imperial College Healthcare NHS Trust
  • England
    • London, England, United Kingdom, NW1 2BU
      • Recruiting
      • University College London Hospitals
    • London, England, United Kingdom, SE1 9RT
      • Recruiting
      • Guy's Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • Recruiting
      • The Christie NHS Foundation Trust
  • London
    • Sutton, London, United Kingdom, SM25PT
      • Recruiting
      • The Royal Marsden NHS Foundation Trust
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX1 2JD
      • Recruiting
      • University of Oxford
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Recruiting
      • Royal Marsden Hospital - Sutton
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02214
      • Recruiting
      • The General Hospital Corporation d/b/a Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Hospital Rochester
  • New York
    • Buffalo, New York, United States, 14263
      • Withdrawn
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center
  • Ohio
    • Hilliard, Ohio, United States, 43026
      • Recruiting
      • James Care Gynecologic Oncology at Mill Run
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Stephenson Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Recruiting
      • Virginia Commonwealth University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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:

   1. serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening)
   2. 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)
   3. documented relapse or progression on or after the most recent line of therapy
   4. no standard therapy options likely to convey clinical benefit
2. Adequate organ and bone marrow function as defined in the protocol
3. Life expectancy of at least 3 months
4. 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.

5. 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:

   1. MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC)
   2. 1-2 prior lines of systemic therapy

Key Exclusion Criteria:

1. Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol
2. Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy
3. Prior treatment with a MUC16 - targeted therapy
4. Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol
5. History and/or current cardiovascular disease, as defined in the protocol
6. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy; REGN4018 administration	Drug: REGN4018; 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.; Other Names: Ubamatamab®; Drug: Sarilumab; Sarilumab will be administered by IV, one-time-only, prior to IV/SC REGN4018.
Experimental: Combination Therapy; REGN4018 and cemiplimab administration	Drug: REGN4018; 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.; Other Names: Ubamatamab®; Drug: cemiplimab; Cemiplimab will be administered by IV infusion after REGN4018 monotherapy lead-in phase.; Other Names: REGN2810

What is the study measuring?

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 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
ORR defined by RECIST 1.1 for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR based on RECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation 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
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 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
ORR based on RECIST 1.1 for REGN4018 monotherapy	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
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
ORR based on iRECIST for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2018
• Primary Completion (Estimated): June 21, 2026
• Study Completion (Estimated): June 21, 2026

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: June 8, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 31, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Recurrence; Ovarian Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Carcinoma, Ovarian Epithelial; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: R4018-ONC-1721; 2019-003298-24 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No