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
- Conditions
- Recurrent Primary Peritoneal CancerRecurrent Endometrial CancerRecurrent Ovarian CancerRecurrent Fallopian Tube Cancer
- Interventions
- Registration Number
- NCT03564340
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 690
-
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:
- serum CA-125 level ≥2 x 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 likely to convey clinical benefit
-
Adequate organ and bone marrow function as defined in the protocol
-
Life expectancy of at least 3 months
-
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.
-
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:
- MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC)
- 1-2 prior lines of systemic therapy
Key
- Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol
- Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy
- Prior treatment with a MUC16 - targeted therapy
- Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol
- History and/or current cardiovascular disease, 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Monotherapy REGN4018 REGN4018 administration Combination Therapy REGN4018 REGN4018 and cemiplimab administration Monotherapy Sarilumab REGN4018 administration Combination Therapy cemiplimab REGN4018 and cemiplimab administration
- Primary Outcome Measures
Name Time Method Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation Phase
Concentration of REGN4018 in serum over time for REGN4018 monotherapy Up to 62 weeks Dose Escalation Phase
Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for REGN4018 monotherapy Up to 62 weeks Dose Escalation Phase
Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation Phase
Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Number of participants with DLTs for REGN4018 with cemiplimab From Cycle 2, Day 1 up to 21 days Dose Escalation Phase
ORR defined by RECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy From Cycle 1, Day 1 up to 35 days Dose Escalation Phase
Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy Up to 62 weeks Dose Escalation Phase
Number of participants with SAEs for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation Phase
Number of deaths for REGN4018 monotherapy Up to 62 weeks Dose Escalation Phase
Number of deaths for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation Phase
Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for REGN4018 monotherapy Up to 62 weeks Dose Escalation Phase
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation Phase
- Secondary Outcome Measures
Name Time Method ORR based on RECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation Phase
ORR based on RECIST 1.1 for REGN4018 monotherapy Up to 62 weeks Dose Escalation Phase
Number of participants with TEAEs (including imAEs) for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Number of participants with SAEs for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Number of participants with SAEs for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Number of deaths for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Number of deaths for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Concentration of REGN4018 in serum over time for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
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 Baseline up to 62 weeks 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 Baseline up to 62 weeks Dose Expansion Phase
Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 monotherapy Baseline up to 62 weeks Dose Expansion Phase
Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 with cemiplimab Baseline up to 62 weeks Dose Expansion Phase
Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for REGN4018 monotherapy Baseline up to 62 weeks 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).Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for REGN4018 with cemiplimab Baseline up to 62 weeks Dose Expansion Phase Not applicable to Endometrial Cancer Cohort
Time to deterioration in GHS/QoL for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Time to deterioration in GHS/QoL for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Time to deterioration in physical functioning for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Time to deterioration in physical functioning for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Time to deterioration in abdominal symptoms for REGN4018 monotherapy Up to 62 weeks Dose Expansion Phase
Time to deterioration in abdominal symptoms for REGN4018 with cemiplimab Up to 62 weeks Dose Expansion Phase
Change from baseline in QoL as measured by EQ-5D for REGN4018 monotherapy Baseline up to 62 weeks Dose Expansion Phase
Change from baseline in QoL as measured by EQ-5D for REGN4018 with cemiplimab Baseline up to 62 weeks Dose Expansion Phase
ORR based on iRECIST for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
ORR based on iRECIST for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
BOR based on iRECIST for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
BOR based on RECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
BOR based on iRECIST for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
DOR based on iRECIST for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
DOR based on RECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
DOR based on iRECIST for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Disease control rate based on RECIST 1.1 for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
Disease control rate based on iRECIST for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Disease control rate based on iRECIST for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
CR rate based on iRECIST 1.1 for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
CR rate based on RECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
PFS based on iRECIST for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
PFS based on RECIST 1.1 for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
PFS based on iRECIST for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Cancer antigen-125 (CA-125) response for REGN4018 monotherapy Up to 62 weeks Dose Escalation and Dose Expansion Phases
CA-125 response for REGN4018 with cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Presence or absence of anti-drug antibodies against REGN4018 Up to 62 weeks Dose Escalation and Dose Expansion Phases
Presence or absence of anti-drug antibodies against cemiplimab Up to 62 weeks Dose Escalation and Dose Expansion Phases
Related Research Topics
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Trial Locations
- Locations (51)
Guys Hospital
🇬🇧London, United Kingdom
Sharet Institute of Oncology
🇮🇱Jerusalem, Israel
University of Alabama_6th Ave
🇺🇸Birmingham, Alabama, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber / Harvard Cancer Center
🇺🇸Boston, Massachusetts, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
The Ohio State University Wexner Medical Center James Comprehensive Cancer Center
🇺🇸Hilliard, Ohio, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University College London Hospitals
🇬🇧London, United Kingdom
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Peter MacCallum Cancer Center
🇦🇺Melbourne, Australia
Prince of Wales Hospital
🇦🇺Randwick, Australia
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Antwerp, Belgium
Grand Hopital de Charleroi
🇧🇪Charleroi, Hainaut, Belgium
UZLeuven
🇧🇪Leuven, Vlaams Brabant, Belgium
Centre Georges Francois Leclerc
🇫🇷Dijon, Bourgogne, France
Institut Gustave Roussy
🇫🇷Villejuif, Ile De France, France
Hopital Lyon Sud
🇫🇷Pierre-Benite, Lyon, France
Centre Francois Baclesse (CFB)
🇫🇷Caen, Normandy, France
Centre Antoine Lacassagne
🇫🇷Nice, Provence Alpes Cote dAzur, France
Institut Bergonie
🇫🇷Bordeaux, France
Rambam Health Care Campus
🇮🇱Haifa, Israel
Sheba Medical Center
🇮🇱Tel Hashomer, Israel
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Lazio, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Instituto Nazionale Tumori- Fondazione Pascale
🇮🇹Naples, Italy
Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center, Univ. of Ulsan
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Radboudumc
🇳🇱Nijmegen, Gelderland, Netherlands
Erasmus MC
🇳🇱Rotterdam, Zuid Holland, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Clinica Universidad de Navarra
🇪🇸Pamplona, Navarra, Spain
Institut Catala dOncologia Badalona
🇪🇸Badalona, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Institut Catala d'Oncologia
🇪🇸Barcelona, Spain
Clinica Universidad Navarra (CUN) Madrid
🇪🇸Madrid, Spain
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario San Carlos
🇪🇸Madrid, Spain
Hospital Clinico Universitatio Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
University of Oxford
🇬🇧Oxford, Oxfordshire, United Kingdom
Royal Marsden Hospital - Sutton
🇬🇧Sutton, Surrey, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, Surrey, United Kingdom
Imperial College Healthcare NHS Trust
🇬🇧London, United Kingdom
The Christie
🇬🇧Manchester, United Kingdom