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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
First received
Last updated
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
Health authority
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 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 Design


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 Korea University Guro Hospital 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 Imperial College Healthcare NHS Trust London
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 Virginia Commonwealth University Medical Center Richmond Virginia
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
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