Clinical trial NCT03564340: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Recurrent Ovarian Cancer
Recurrent Fallopian Tube Cancer
Recurrent Primary Peritoneal Cancer
Recurrent Endometrial Cancer
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-06-20
Enrollment: 690
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with Dose-limiting toxicity (DLTs) for REGN4018 monotherapy
timeFrame: From Cycle 1, Day 1 up to 35 days
measure: Number of participants with DLTs for REGN4018 with cemiplimab
timeFrame: From Cycle 2, Day 1 up to 21 days
measure: Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Number of participants with serious adverse events (SAEs) for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of participants with SAEs for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Number of deaths for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of deaths for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Concentration of REGN4018 in serum over time for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: ORR defined by RECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
Secondary outcomes:
measure: ORR based on RECIST 1.1 for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: ORR based on RECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Number of participants with TEAEs (including imAEs) for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of participants with TEAEs (including imAEs) for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Number of participants with SAEs for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of participants with SAEs for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Number of deaths for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of deaths for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Concentration of REGN4018 in serum over time for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Concentration of REGN4018 in serum over time for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: 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
timeFrame: Baseline up to 62 weeks
measure: 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
timeFrame: Baseline up to 62 weeks
measure: Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 monotherapy
timeFrame: Baseline up to 62 weeks
measure: Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for REGN4018 with cemiplimab
timeFrame: Baseline up to 62 weeks
measure: Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for REGN4018 monotherapy
timeFrame: Baseline up to 62 weeks
measure: Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for REGN4018 with cemiplimab
timeFrame: Baseline up to 62 weeks
measure: Time to deterioration in GHS/QoL for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Time to deterioration in GHS/QoL for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Time to deterioration in physical functioning for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Time to deterioration in physical functioning for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Time to deterioration in abdominal symptoms for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Time to deterioration in abdominal symptoms for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Change from baseline in QoL as measured by EQ-5D for REGN4018 monotherapy
timeFrame: Baseline up to 62 weeks
measure: Change from baseline in QoL as measured by EQ-5D for REGN4018 with cemiplimab
timeFrame: Baseline up to 62 weeks
measure: ORR based on iRECIST for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: ORR based on iRECIST for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Best overall response (BOR) based on RECIST 1.1 for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: BOR based on iRECIST for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: BOR based on RECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: BOR based on iRECIST for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Duration of response (DOR) based on RECIST 1.1 for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: DOR based on iRECIST for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: DOR based on RECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: DOR based on iRECIST for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Disease control rate based on RECIST 1.1 for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Disease control rate based on iRECIST for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: Disease control rate based on RECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Disease control rate based on iRECIST for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Complete response (CR) rate based on RECIST 1.1 for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: CR rate based on iRECIST 1.1 for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: CR rate based on RECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: CR rate based on iRECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Progression-free survival (PFS) based on RECIST 1.1 for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: PFS based on iRECIST for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: PFS based on RECIST 1.1 for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: PFS based on iRECIST for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Cancer antigen-125 (CA-125) response for REGN4018 monotherapy
timeFrame: Up to 62 weeks
measure: CA-125 response for REGN4018 with cemiplimab
timeFrame: Up to 62 weeks
measure: Presence or absence of anti-drug antibodies against REGN4018
timeFrame: Up to 62 weeks
measure: Presence or absence of anti-drug antibodies against cemiplimab
timeFrame: Up to 62 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama_6th Ave
state: Alabama
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber / Harvard Cancer Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Hilliard
country: United States
facility: The Ohio State University Wexner Medical Center James Comprehensive Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
city: Randwick
country: Australia
facility: Prince of Wales Hospital
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
state: Antwerp
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
state: Hainaut
city: Leuven
country: Belgium
facility: UZLeuven
state: Vlaams Brabant
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
state: Bourgogne
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Ile De France
city: Pierre-Benite
country: France
facility: Hopital Lyon Sud
state: Lyon
city: Caen
country: France
facility: Centre Francois Baclesse (CFB)
state: Normandy
city: Nice
country: France
facility: Centre Antoine Lacassagne
state: Provence Alpes Cote dAzur
city: Bordeaux
country: France
facility: Institut Bergonie
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Sharet Institute of Oncology
city: Tel Hashomer
country: Israel
facility: Sheba Medical Center
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
state: Lazio
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Naples
country: Italy
facility: Instituto Nazionale Tumori- Fondazione Pascale
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Univ. of Ulsan
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Nijmegen
country: Netherlands
facility: Radboudumc
state: Gelderland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Badalona
country: Spain
facility: Institut Catala dOncologia Badalona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia
city: Madrid
country: Spain
facility: Clinica Universidad Navarra (CUN) Madrid
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Santiago de Compostela
country: Spain
facility: Hospital Clinico Universitatio Santiago de Compostela
city: Oxford
country: United Kingdom
facility: University of Oxford
state: Oxfordshire
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital - Sutton
state: Surrey
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
city: London
country: United Kingdom
facility: University College London Hospitals
city: London
country: United Kingdom
facility: Guys Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: