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NCT03564340PHASE1, PHASE2Recruiting

Study of REGN4018 (Ubamatamab) Administered Alone or in Combination With Cemiplimab in Adult Patients With Recurrent Ovarian Cancer or Other Recurrent Mucin-16 Expressing (MUC16+) Cancers

Regeneron Pharmaceuticals

Start Date

5/21/2018

Completion Date

5/10/2027

Summary

The main purpose of this study is to: * Learn about the safety of ubamatamab and to find out what dose of ubamatamab 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 ubamatamab and/or cemiplimab in the body and measure how well the body can remove the study drug(s). This is called pharmacokinetics * The study will also look at any signs that ubamatamab alone or with cemiplimab can treat recurrent advanced ovarian cancer or cancer of the uterus * To find out how safe and tolerable pretreatment is in combination with ubamatamab and to see how well it works to prevent or minimize Cytokine Release Syndrome (CRS)

Eligibility Criteria

Age Range: 18 years to No maximum

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, not required for low-grade serous carcinoma) 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 2 to 4 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), as defined in the protocol 2. 1-4 prior lines of systemic therapy, as described in the protocol 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 (does not apply to low-grade serous ovarian cancer cohort) 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-defined Inclusion/Exclusion Criteria apply

Interventions

DRUG

Ubamatamab

DRUG

Cemiplimab

DRUG

Sarilumab

DRUG

Tocilizumab

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Conditions

Recurrent Ovarian CancerRecurrent Fallopian Tube CancerRecurrent Primary Peritoneal CancerRecurrent Endometrial CancerEndometrial CancerLow-grade Serous Ovarian Cancer

Locations

University of Alabama_6th Ave

Birmingham, Alabama 35294

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana Farber / Harvard Cancer Center

Boston, Massachusetts 02215

United States

Mayo Clinic - Rochester

Rochester, Minnesota 55901

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Columbia University Medical Center

New York, New York 10032

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

The Ohio State University Wexner Medical Center

Columbus, Ohio 43210

United States

Stephenson Cancer Center

Oklahoma City, Oklahoma 73104

United States

Sarah Cannon Research Institute

Nashville, Tennessee 37203

United States

Virginia Commonwealth University

Richmond, Virginia 23219

United States

Prince of Wales Hospital

Randwick, New South Wales 2031

Australia

Peter MacCallum Cancer Center

Melbourne, 3000

Australia

Universitair Ziekenhuis Antwerpen

Edegem, Antwerp 2650

Belgium

Grand Hopital de Charleroi

Charleroi, Hainaut 6000

Belgium

UZLeuven

Leuven, Vlaams-Brabant 3000

Belgium

Hopital Lyon Sud

Pierre-Bénite, Auvergne-Rhône 69310

France

Centre Georges Francois Leclerc

Dijon, Bourgogne-Franche-Comté 21000

France

Institut Bergonie

Bordeaux, New Aquitaine 33076

France

Centre Francois Baclesse (CFB)

Caen, Normandy 14076

France

Centre Antoine Lacassagne

Nice, Provence Alpes Cote dAzur 06189

France

Institut Gustave Roussy

Villejuif, Île-de-France Region 94800

France

Rambam Health Care Campus

Haifa, 3109601

Israel

Sharet Institute of Oncology

Jerusalem, 9112001

Israel

Sheba Medical Center

Tel Litwinsky, 5265601

Israel

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio 00168

Italy

Humanitas S. Pio X

Milan, 20159

Italy

Istituto Europeo di Oncologia

Milan, 20141

Italy

Instituto Nazionale Tumori- Fondazione Pascale

Naples, 80131

Italy

Radboudumc

Nijmegen, Gelderland 6500HB

Netherlands

Erasmus MC

Rotterdam, South Holland 3000 DR

Netherlands

University Medical Center Groningen

Groningen, 9713 GZ

Netherlands

Yonsei University Health System

Seoul, 03722

South Korea

Asan Medical Center, Univ. of Ulsan

Seoul, 05505

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Korea University Guro Hospital

Seoul, 08307

South Korea

Seoul National University Hospital

Seoul, 3080

South Korea

Clinica Universidad de Navarra

Pamplona, Navarre 31008

Spain

Institut Catala dOncologia Badalona

Badalona, 08916

Spain

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Institut Catala d'Oncologia

Barcelona, 8908

Spain

Clinica Universidad Navarra (CUN) Madrid

Madrid, 28027

Spain

Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario San Carlos

Madrid, 28040

Spain

Hospital Clinico Universitatio Santiago de Compostela

Santiago de Compostela, 15706

Spain

University of Oxford

Oxford, Oxfordshire OX1 2JD

United Kingdom

Royal Marsden Hospital - Sutton

Sutton, Surrey SM2 5PT

United Kingdom

The Royal Marsden NHS Foundation Trust

Sutton, Surrey SM2 5PT

United Kingdom

University College London Hospitals

London, NW1 2PG

United Kingdom

Guys Hospital

London, SE1 9RT

United Kingdom

Imperial College Healthcare NHS Trust

London, W12 0HS

United Kingdom

The Christie NHS Foundation Trust

Manchester, M20 4BX

United Kingdom