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

Recurrent Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03564340
• Other study ID #: R4018-ONC-1721
• Secondary ID: 2019-003298-24
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 21, 2018
• Est. completion date: June 21, 2026

Study information

• Verified date: December 2023
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 690
• Est. completion date: June 21, 2026
• Est. primary completion date: June 21, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 cardiac findings 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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Endometrial Neoplasms
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Recurrence
• Recurrent Endometrial Cancer
• Recurrent Fallopian Tube Cancer
• Recurrent Ovarian Cancer
• Recurrent Primary Peritoneal Cancer

Intervention

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.
• cemiplimab
Cemiplimab will be administered by IV infusion after REGN4018 monotherapy lead-in phase.
• Sarilumab
Sarilumab will be administered by IV, one-time-only, prior to IV/SC REGN4018.

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Center	Melbourne	Victoria
Australia	Prince of Wales Hospital	Randwick	New South Wales
Belgium	Grand Hôpital de Charleroi	Charleroi	Hainaut
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Antwerp
Belgium	UZLeuven	Leuven	Vlaams Brabant
France	Centre Regional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest - Institut Bergonie	Bordeaux
France	UNICANCER - Centre Francois Baclesse (CFB)	Caen cedex 5
France	Centre Georges-Francois Leclerc	Dijon cedex	Bourgogne
France	Centre Antoine Lacassagne	Nice	Cedex 2
France	Centre Hospitalier Lyon Sud, Hospices Civils de Lyon	Pierre-Benite	Lyon
France	Institut Gustave Roussy	Villejuif Cedex
Israel	Rambam Health Care Campus RHCC - Rambam Medical Center	Haifa
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Italy	Istituto Europeo di Oncologia	Milano
Italy	Instituto Nazionale Tumori- Fondazione Pascale	Naples
Italy	Fondazione Policlinico Agostino Gemelli IRCCS di Roma	Roma	Lazio
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University College of Medicine	Seoul
Korea, Republic of	Yonsei University Health System	Seoul
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Radboudumc, dept Medical Oncology hp 452	Nijmegen	Gelderland
Netherlands	Erasmus MC	Rotterdam	Zuid Holland
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Institut Catala d'Oncologia	Barcelona
Spain	Institut Catala d'Oncologia	Barcelona
Spain	Clinica Universidad de Navarra	Madrid	Navarre
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitario San Carlos	Madrid
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Clinico Universitatio Santiago de Compostela	Santiago de Compostela
United Kingdom	Guy's Hospital	London	England
United Kingdom	University College London Hospitals	London	England
United Kingdom	The Christie NHS Foundation Trust	Manchester	Greater Manchester
United Kingdom	University of Oxford	Oxford	Oxfordshire
United Kingdom	Royal Marsden Hospital - Sutton	Sutton	Surrey
United Kingdom	The Royal Marsden NHS Foundation Trust	Sutton	London
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	The General Hospital Corporation d/b/a Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	James Care Gynecologic Oncology at Mill Run	Hilliard	Ohio
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Columbia University Irving Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Mayo Clinic Hospital Rochester	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Israel,  Italy,  Korea, Republic of,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy	Dose Escalation Phase	From Cycle 1, Day 1 up to 35 days
Primary	Number of participants with DLTs for REGN4018 with cemiplimab	Dose Escalation Phase	From Cycle 2, Day 1 up to 21 days
Primary	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
Primary	Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab	Dose Escalation Phase	Up to 62 weeks
Primary	Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy	Dose Escalation Phase	Up to 62 weeks
Primary	Number of participants with SAEs for REGN4018 with cemiplimab	Dose Escalation Phase	Up to 62 weeks
Primary	Number of deaths for REGN4018 monotherapy	Dose Escalation Phase	Up to 62 weeks
Primary	Number of deaths for REGN4018 with cemiplimab	Dose Escalation Phase	Up to 62 weeks
Primary	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
Primary	Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab	Dose Escalation Phase	Up to 62 weeks
Primary	Concentration of REGN4018 in serum over time for REGN4018 monotherapy	Dose Escalation Phase	Up to 62 weeks
Primary	Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab	Dose Escalation Phase	Up to 62 weeks
Primary	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
Primary	ORR defined by RECIST 1.1 for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	ORR based on RECIST 1.1 for REGN4018 monotherapy	Dose Escalation Phase	Up to 62 weeks
Secondary	ORR based on RECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation Phase	Up to 62 weeks
Secondary	Number of participants with TEAEs (including imAEs) for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	Number of participants with SAEs for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Number of participants with SAEs for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	Number of deaths for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Number of deaths for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	Concentration of REGN4018 in serum over time for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to deterioration in GHS/QoL for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Time to deterioration in GHS/QoL for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	Time to deterioration in physical functioning for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Time to deterioration in physical functioning for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	Time to deterioration in abdominal symptoms for REGN4018 monotherapy	Dose Expansion Phase	Up to 62 weeks
Secondary	Time to deterioration in abdominal symptoms for REGN4018 with cemiplimab	Dose Expansion Phase	Up to 62 weeks
Secondary	Change from baseline in QoL as measured by EQ-5D for REGN4018 monotherapy	Dose Expansion Phase	Baseline up to 62 weeks
Secondary	Change from baseline in QoL as measured by EQ-5D for REGN4018 with cemiplimab	Dose Expansion Phase	Baseline up to 62 weeks
Secondary	ORR based on iRECIST for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	ORR based on iRECIST for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	BOR based on iRECIST for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	BOR based on RECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	BOR based on iRECIST for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	DOR based on iRECIST for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	DOR based on RECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	DOR based on iRECIST for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Disease control rate based on RECIST 1.1 for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Disease control rate based on iRECIST for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Disease control rate based on iRECIST for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	CR rate based on iRECIST 1.1 for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	CR rate based on RECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	PFS based on iRECIST for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	PFS based on RECIST 1.1 for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	PFS based on iRECIST for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Cancer antigen-125 (CA-125) response for REGN4018 monotherapy	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	CA-125 response for REGN4018 with cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Presence or absence of anti-drug antibodies against REGN4018	Dose Escalation and Dose Expansion Phases	Up to 62 weeks
Secondary	Presence or absence of anti-drug antibodies against cemiplimab	Dose Escalation and Dose Expansion Phases	Up to 62 weeks