Recurrent Ovarian CancerPhase 1/2NCT03564340
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
A Phase 1/2 study testing Ubamatamab, Cemiplimab and Sarilumab in people with Recurrent Ovarian Cancer and Recurrent Fallopian Tube Cancer, run by Regeneron Pharmaceuticals at 54 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Ovarian Cancer, Recurrent Fallopian Tube Cancer, Recurrent Primary Peritoneal Cancer
- What is being tested?
- Ubamatamab, Cemiplimab and Sarilumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 890 participants
- Where
- 54 sitesin 10 countries
- Study dates
- 21 May 2018to 10 May 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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, not required for low-grade serous carcinoma)
- 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
Show all 11Show fewer
- Life expectancy of at least 3 months
- 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.
- 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), as defined in the protocol
- 1-4 prior lines of systemic therapy, as described in the protocol
Who cannot join
- 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 (does not apply to low-grade serous ovarian cancer cohort)
- 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-defined Inclusion/Exclusion Criteria apply
Trial locations and contacts
54 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
54 sites in 10 countries
United States12 sites, 10 recruiting
- Recruiting
University of Alabama_6th Ave
Birmingham, Alabama, 35294
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
Dana Farber / Harvard Cancer Center
Boston, Massachusetts, 02215
- Withdrawn
Roswell Park Cancer Institute
Buffalo, New York, 14263
- Recruiting
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
- Completed
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
- Recruiting
Columbia University Medical Center
New York, New York, 10032
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
- Recruiting
Virginia Commonwealth University
Richmond, Virginia, 23219
- Recruiting
Mayo Clinic - Rochester
Rochester, Minnesota, 55901
Spain8 sites, 8 recruiting
- Recruiting
Institut Catala dOncologia Badalona
Badalona, 08916
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
- Recruiting
Institut Catala d'Oncologia
Barcelona, 08908
- Recruiting
Clinica Universidad Navarra (CUN) Madrid
Madrid, 28027
- Recruiting
Fundacion Jimenez Diaz
Madrid, 28040
- Recruiting
Hospital Universitario San Carlos
Madrid, 28040
- Recruiting
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
- Recruiting
Hospital Clinico Universitatio Santiago de Compostela
Santiago de Compostela, 15706
France7 sites, 7 recruiting
- Recruiting
Institut Bergonie
Bordeaux, New Aquitaine, 33076
- Recruiting
Centre Francois Baclesse (CFB)
Caen, Normandy, 14076
- Recruiting
Centre Georges Francois Leclerc
Dijon, Bourgogne-Franche-Comté, 21000
- Recruiting
Centre Leon Berard
Lyon, 69008
- Recruiting
Centre Antoine Lacassagne
Nice, Provence Alpes Cote dAzur, 06189
- Recruiting
Hopital Lyon Sud
Pierre-Bénite, Auvergne-Rhône, 69310
- Recruiting
Institut Gustave Roussy
Villejuif, Île-de-France Region, 94800
United Kingdom7 sites, 6 recruiting
- Recruiting
University College London Hospitals
London, NW1 2PG
- Recruiting
Guys Hospital
London, SE1 9RT
- Recruiting
Imperial College Healthcare NHS Trust
London, W12 0HS
- Recruiting
The Christie NHS Foundation Trust
Manchester, M20 4BX
- Recruiting
University of Oxford
Oxford, Oxfordshire, OX1 2JD
- Withdrawn
Royal Marsden Hospital - Sutton
Sutton, Surrey, SM2 5PT
- Recruiting
The Royal Marsden NHS Foundation Trust
Sutton, Surrey, SM2 5PT
South Korea5 sites, 5 recruiting
- Recruiting
Yonsei University Health System
Seoul, 03722
- Recruiting
Asan Medical Center, Univ. of Ulsan
Seoul, 05505
- Recruiting
Samsung Medical Center
Seoul, 06351
- Recruiting
Korea University Guro Hospital
Seoul, 08307
- Recruiting
Seoul National University Hospital
Seoul, 3080
Italy4 sites, 4 recruiting
- Recruiting
Humanitas S. Pio X
Milan, 20159
- Recruiting
Istituto Europeo di Oncologia
Milan, 20141
- Recruiting
Instituto Nazionale Tumori- Fondazione Pascale
Naples, 80131
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Rome, Lazio, 00168
Belgium3 sites, 3 recruiting
- Recruiting
Grand Hopital de Charleroi
Charleroi, Hainaut, 6000
- Recruiting
Universitair Ziekenhuis Antwerpen
Edegem, Antwerp, 2650
- Recruiting
UZLeuven
Leuven, Vlaams-Brabant, 3000
Israel3 sites, 3 recruiting
- Recruiting
Rambam Health Care Campus
Haifa, 3109601
- Recruiting
Sharet Institute of Oncology
Jerusalem, 9112001
- Recruiting
Sheba Medical Center
Tel Litwinsky, 5265601
Netherlands3 sites, 3 recruiting
- Recruiting
University Medical Center Groningen
Groningen, 9713 GZ
- Recruiting
Radboudumc
Nijmegen, Gelderland, 6500HB
- Recruiting
Erasmus MC
Rotterdam, South Holland, 3000 DR
Australia2 sites
- Completed
Peter MacCallum Cancer Center
Melbourne, 3000
- Completed
Prince of Wales Hospital
Randwick, New South Wales, 2031
About this study
Official title: A Phase 1/2 Study of REGN4018 (Ubamatamab), a MUC16×CD3 Bispecific Antibody, Administered Alone or in Combination With Cemiplimab in Patients With Recurrent Ovarian Cancer or Other Recurrent MUC16+ Cancers
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)
- Conditions
- Recurrent Ovarian Cancer, Recurrent Fallopian Tube Cancer, Recurrent Primary Peritoneal Cancer, Recurrent Endometrial Cancer, Endometrial Cancer, Low-grade Serous Ovarian Cancer
- Being tested
- Ubamatamab, Cemiplimab, Sarilumab, Tocilizumab
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms, Endometrial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UbamatamabDrug
Also called REGN4018
Administered per the protocol
CemiplimabDrug
Also called REGN2810, Libtayo®
Administered per the protocol
SarilumabDrug
Also called Kevzara®, REGN88, SAR153191
Administered per the protocol
TocilizumabDrug
Also called ACTEMRA®, Biosimilar
Administered per the protocol
| Study group | Role | What they receive |
|---|---|---|
| Monotherapy | Experimental | REGN4018 administration Receives: Drug: Ubamatamab; Drug: Sarilumab; Drug: Tocilizumab |
| Combination Therapy | Experimental | REGN4018 and cemiplimab administration Receives: Drug: Ubamatamab; Drug: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Dose-limiting toxicity (DLTs) for ubamatamab monotherapy
Dose Escalation Phase
Measured: From Cycle 1, Day 1 up to 35 days
Number of participants with DLTs for ubamatamab with cemiplimab
Dose Escalation Phase
Measured: From Cycle 2, Day 1 up to 21 days
Number of participants with Treatment-emergent adverse event (TEAE)s (including immune-related adverse events (imAEs)) for ubamatamab monotherapy
Dose Escalation Phase
Measured: Up to 2 years
Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab
Dose Escalation Phase
Measured: Up to 2 years
Number of participants with serious adverse events (SAEs) for ubamatamab monotherapy
Dose Escalation Phase
Measured: Up to 2 years
Number of participants with SAEs for ubamatamab with cemiplimab
Dose Escalation Phase
Measured: Up to 2 years
Number of deaths for ubamatamab monotherapy
Dose Escalation Phase
Measured: Up to 2 years
Number of deaths for ubamatamab with cemiplimab
Dose Escalation Phase
Measured: Up to 2 years
Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for ubamatamab monotherapy
Dose Escalation Phase
Measured: Up to 2 years
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab
Dose Escalation Phase
Measured: Up to 2 years
Concentration of ubamatamab in serum over time for ubamatamab monotherapy
Dose Escalation Phase
Measured: Up to 2 years
Concentration of ubamatamab in serum over time for ubamatamab with cemiplimab
Dose Escalation Phase
Measured: Up to 2 years
Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
ORR defined by RECIST 1.1 for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Secondary outcomes (52)
ORR based on RECIST 1.1 for ubamatamab monotherapy
Dose Escalation Phase
Measured: Up to 2 years
ORR based on RECIST 1.1 for ubamatamab with cemiplimab
Dose Escalation Phase
Measured: Up to 2 years
Number of participants with TEAEs (including imAEs) for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Number of participants with TEAEs (including imAEs) for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Number of participants with SAEs for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Number of participants with SAEs for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Number of deaths for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Number of deaths for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Concentration of ubamatamab in serum over time for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Concentration of ubamatamab in serum over time for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
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 ubamatamab 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."
Measured: Baseline up to 2 years
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 ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Baseline up to 2 years
Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab monotherapy
Dose Expansion Phase
Measured: Baseline up to 2 years
Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Baseline up to 2 years
Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score for ubamatamab 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).
Measured: Baseline up to 2 years
Change from baseline in abdominal symptoms as measured by the MOST-Abdominal index score for ubamatamab with cemiplimab
Dose Expansion Phase Not applicable to Endometrial Cancer Cohort
Measured: Baseline up to 2 years
Time to deterioration in GHS/QoL for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Time to deterioration in GHS/QoL for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Time to deterioration in physical functioning for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Time to deterioration in physical functioning for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Time to deterioration in abdominal symptoms for ubamatamab monotherapy
Dose Expansion Phase
Measured: Up to 2 years
Time to deterioration in abdominal symptoms for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Up to 2 years
Change from baseline in QoL as measured by EQ-5D for ubamatamab monotherapy
Dose Expansion Phase
Measured: Baseline up to 2 years
Change from baseline in QoL as measured by EQ-5D for ubamatamab with cemiplimab
Dose Expansion Phase
Measured: Baseline up to 2 years
ORR based on iRECIST for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
ORR based on iRECIST for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Best overall response (BOR) based on RECIST 1.1 for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
BOR based on iRECIST for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
BOR based on RECIST 1.1 for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
BOR based on iRECIST for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Duration of response (DOR) based on RECIST 1.1 for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
DOR based on iRECIST for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
DOR based on RECIST 1.1 for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
DOR based on iRECIST for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Disease control rate based on RECIST 1.1 for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Disease control rate based on iRECIST for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Disease control rate based on RECIST 1.1 for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Disease control rate based on iRECIST for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Complete response (CR) rate based on RECIST 1.1 for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
CR rate based on iRECIST 1.1 for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
CR rate based on RECIST 1.1 for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
CR rate based on iRECIST 1.1 for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Progression-free survival (PFS) based on RECIST 1.1 for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
PFS based on iRECIST for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
PFS based on RECIST 1.1 for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
PFS based on iRECIST for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Cancer antigen-125 (CA-125) response for ubamatamab monotherapy
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
CA-125 response for ubamatamab with cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Presence or absence of anti-drug antibodies against ubamatamab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Presence or absence of anti-drug antibodies against cemiplimab
Dose Escalation and Dose Expansion Phases
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2018
- Study start21 May 2018
- Primary completion10 May 2027 (estimated)
- Study completion10 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 890 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03564340
- Sponsor's protocol ID
- R4018-ONC-1721
- Other IDs
- 2024-510783-23-00, 2019-003298-24, 2019
- Status last verified
- Sep 2026
- First submitted
- 17 May 2018
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Publications
Zhu M, Madia P, Crawford A, Brouwer-Visser J, Krueger P, Haber L, Peterman M, Uldrick TS, Miller E, Davis JD, Retter MW. Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 x CD3 bispecific antibody) in patients with recurrent ovarian cancer. Clin Transl Sci. 2024 Dec;17(12):e70082. doi: 10.1111/cts.70082.
PubMed 39652449