Clinical trial • Phase I/II • Oncology

UBAMATAMAB for Ovarian cancer | Endometrial cancer | Fallopian tube cancer | Primary peritoneal cancer

Phase I/II trial of UBAMATAMAB for Ovarian cancer | Endometrial cancer | Fallopian tube cancer | Primary peritoneal cancer. Randomised, adaptive.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Ovarian cancer | Endometrial cancer | Fallopian tube cancer | Primary peritoneal cancer
Trial Stage
Phase I/II
Drug Modality
Bispecific antibody | Monoclonal antibody

Key dates

Initial CTIS Submission Date
28-05-2024
First CTIS Authorization Date
25-06-2024

Trial design

Randomised, adaptive Phase I/II trial in Netherlands, Belgium, France and others.

Randomised
Yes
Adaptive
Yes
Biomarker Stratified
True, MUC16 tumor expression (MUC16 positivity ≥25% by IHC used for endometrial cohorts)
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
452

Eligibility

Recruits 452 No vulnerable populations selected (isVulnerablePopulationSelected: false). Trial enrolls adult patients only (public title and population indicate adult patients). Informed consent is obtained from adult participants; assent is not applicable..

Vulnerable Population
No vulnerable populations selected (isVulnerablePopulationSelected: false). Trial enrolls adult patients only (public title and population indicate adult patients). Informed consent is obtained from adult participants; assent is not applicable.

Inclusion criteria

  • {"criterion_text":"- 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: a. serum CA-125 level ≥2 x upper limit of normal (ULN) (in screening), not required for low-grade serous carcinoma); b. 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\n- Adequate organ and bone marrow function as defined in the protocol\n- Life expectancy of at least 3 months\n- 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.\n- 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: a. MUC16 positivity of tumor cells ≥25% by immunohistochemistry (IHC), as defined in the protocol; b. 1-4 prior lines of systemic therapy, as described in the protocol\n- Other protocol-defined inclusion criteria apply"}

Exclusion criteria

  • {"criterion_text":"- Prior treatment with anti-Programmed Cell Death (PD-1)/PD-L1 therapy, as described in the protocol\n- Ovarian Cancer Expansion cohorts only: More than 4 prior lines of cytotoxic chemotherapy (does not apply to low-grade serous ovarian cancer cohort)\n- Prior treatment with a MUC16 - targeted therapy\n- Untreated or active primary brain tumor, central nervous system (CNS) metastases, or spinal cord compression, as described in the protocol\n- History and/or current cardiac findings as defined in the protocol\n- Severe and/or uncontrolled hypertension at screening. Patients taking anti-hypertensive medication must be on a stable anti-hypertensive regimen\n- Other protocol-defined exclusion criteria apply"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- In the Dose Escalation Phase: Number of participants with Dose-limiting toxicity (DLTs) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Count of participants experiencing dose-limiting toxicity (DLT) during the Dose Escalation Phase for ubamatamab monotherapy and in combination with cemiplimab"}
  • {"endpoint_text":"- In the Dose Escalation Phase: Number of participants with Treatment-emergent adverse event (TEAE)s (including immune (imAEs)) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Count of participants with treatment-emergent adverse events (including immune-related AEs) during Dose Escalation Phase for ubamatamab monotherapy and in combination with cemiplimab"}
  • {"endpoint_text":"- In the Dose Escalation Phase: Number of participants with serious adverse events (SAEs) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Count of participants experiencing serious adverse events during Dose Escalation Phase for ubamatamab monotherapy and in combination with cemiplimab"}
  • {"endpoint_text":"- In the Dose Escalation Phase: Number of deaths for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Number of deaths observed during Dose Escalation Phase for ubamatamab monotherapy and in combination with cemiplimab"}
  • {"endpoint_text":"- In the Dose Escalation Phase: Number of participants with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Count of participants with laboratory abnormalities grade ≥3 per CTCAE during Dose Escalation Phase"}
  • {"endpoint_text":"- In the Dose Escalation Phase: Concentration of REGN4018 in serum over time for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Pharmacokinetic measurement: serum concentration of REGN4018 (ubamatamab) over time"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Objective response rate (ORR) defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"ORR as defined by RECIST 1.1 in Dose Expansion Phase for ubamatamab monotherapy and in combination with cemiplimab"}

Secondary endpoints

  • {"endpoint_text":"- In the Dose Escalation Phase: ORR based on RECIST 1.1 for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Objective response rate (RECIST 1.1) during Dose Escalation Phase"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Number of participants with TEAEs (including imAEs) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Count of treatment-emergent adverse events (including immune AEs) in Dose Expansion Phase"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Number of participants with SAEs for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Count of serious adverse events in Dose Expansion Phase"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Number of deaths for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Number of deaths in Dose Expansion Phase"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Number of participants with laboratory abnormalities (grade 3 or higher per CTCAE) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Count of grade ≥3 laboratory abnormalities per CTCAE in Dose Expansion Phase"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Concentration of ubamatamab in serum over time for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Pharmacokinetic measurement: serum concentration of ubamatamab over time in Dose Expansion Phase"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Change from baseline in 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 and in combination with cemiplimab","definition_or_measurement_approach":"Change from baseline in EORTC QLQ-C30 Global Health Status/Quality of Life score"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Change from baseline in physical functioning as measured by the EORTC QLQ-C30 physical functioning score for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Change from baseline in EORTC QLQ-C30 physical functioning score"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Change from baseline in abdominal symptoms as measured by the Measure of Ovarian Symptoms and Treatment (MOST)-Abdominal index score (Not applicable to Endometrial Cancer Cohort) for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Change from baseline in MOST-Abdominal index score (ovarian symptom measure); not applicable to Endometrial Cancer cohort"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Time to deterioration in GHS/QoL, physical functioning, and abdominal symptoms for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Time-to-event analysis for deterioration in GHS/QoL, physical functioning, and abdominal symptoms"}
  • {"endpoint_text":"- In the Dose Expansion Phase: Change from baseline in QoL as measured by EQ-5D for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Change from baseline in EQ-5D quality of life measure"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: ORR based on iRECIST for ubamatamab monotherapy and with cemiplimab","definition_or_measurement_approach":"Objective response rate per iRECIST across Dose Escalation and Expansion Phases"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: Best overall response (BOR) based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Best overall response assessed by RECIST 1.1 and iRECIST"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: Duration of response (DOR) based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Duration of response per RECIST 1.1 and iRECIST"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: Disease control rate based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Disease control rate per RECIST 1.1 and iRECIST"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: Progression-free survival (PFS) based on RECIST 1.1 and iRECIST for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Progression-free survival per RECIST 1.1 and iRECIST"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: Complete Response (CR) rate for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"Complete response rate as assessed by RECIST/iRECIST"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: Cancer antigen-125 (CA-125) response for ubamatamab monotherapy and in combination with cemiplimab","definition_or_measurement_approach":"CA-125 biomarker response measured per protocol"}
  • {"endpoint_text":"- In the Dose Escalation and Dose Expansion Phase: Presence or absence of anti-drug antibodies against ubamatamab and cemiplimab","definition_or_measurement_approach":"Assessment of immunogenicity: presence/absence of anti-drug antibodies against ubamatamab and cemiplimab"}

Recruitment

Planned Sample Size
452
Recruitment Window Months
97
Consent Approach
Informed consent obtained from adult participants. Subject information sheets and informed consent forms (L1_SIS and ICF) are provided in multiple languages (English, Dutch/NL, French/FR/BE, Italian, Spanish and country variants) and separate ICFs are present for genomics and pregnancy/birth substudies (separate genomics and pregnancy ICF documents listed).

Methods

  • K1_Recruitment Procedure / K1_Recruitment arrangements documents present (country-specific recruitment arrangements documents listed for NL, BE, IT, ES)
  • K2 recruitment materials including GP letter / Dear Dr Letter (indicates outreach to referring physicians/GPs)
  • Site-based recruitment at listed hospital/clinic trial sites (site contact details provided in country Part II records)
  • Recruitment materials / subject ID card (document titles present)

Geography

Total Number Of Sites
25
Total Number Of Participants
237

Netherlands

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
11-07-2024
Processing Time Days
35
Number Of Sites
3
Number Of Participants
20

Sites

Site Name
Universitair Medisch Centrum Groningen
Department Name
Medical Oncology
Principal Investigator Name
Anna Reyners
Principal Investigator Email
a.k.l.reyners@umcg.nl
Contact Person Name
Anna Reyners
Contact Person Email
a.k.l.reyners@umcg.nl
Site Name
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Department Name
Internal Oncology
Principal Investigator Name
Ingrid Boere
Principal Investigator Email
i.boere@erasmusmc.nl
Contact Person Name
Ingrid Boere
Contact Person Email
i.boere@erasmusmc.nl
Site Name
Stichting Radboud universitair medisch centrum
Department Name
Medical Oncology
Principal Investigator Name
Vicky Soomers
Principal Investigator Email
vicky.soomers@radboudumc.nl
Contact Person Name
Vicky Soomers
Contact Person Email
vicky.soomers@radboudumc.nl

Belgium

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
25-06-2024
Processing Time Days
19
Number Of Sites
3
Number Of Participants
66

Sites

Site Name
Grand Hopital De Charleroi
Department Name
Oncology and Haematology
Principal Investigator Name
David Schroder
Principal Investigator Email
David.SCHRODER@ghdc.be
Contact Person Name
David Schroder
Contact Person Email
David.SCHRODER@ghdc.be
Site Name
UZ Leuven
Department Name
Gynaecological Oncology
Principal Investigator Name
Els Van Nieuwenhuysen
Principal Investigator Email
els.vannieuwenhuysen@uzleuven.be
Contact Person Name
Els Van Nieuwenhuysen
Site Name
Antwerp University Hospital
Department Name
Oncology
Principal Investigator Name
Konstantinos Papadimitriou
Principal Investigator Email
Konstantinos.papadimitriou@uza.be
Contact Person Name
Konstantinos Papadimitriou

France

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
09-07-2024
Processing Time Days
33
Number Of Sites
7
Number Of Participants
51

Sites

Site Name
Institut Gustave Roussy
Department Name
Medical Oncology
Principal Investigator Name
Judith Michels
Principal Investigator Email
judith.michels@gustaveroussy.fr
Contact Person Name
Judith Michels
Site Name
Hospices Civils De Lyon
Department Name
Medical Oncology
Principal Investigator Name
Benoit You
Principal Investigator Email
benoit.you@chu-lyon.fr
Contact Person Name
Benoit You
Contact Person Email
benoit.you@chu-lyon.fr
Site Name
Centre Antoine Lacassagne
Department Name
Provence Alpes Cote dAzur
Principal Investigator Name
Follana Philippe
Principal Investigator Email
philippe.follana@nice.unicancer.fr
Contact Person Name
Follana Philippe
Site Name
Centr Georges Francois Leclerc
Department Name
Medical Oncology
Principal Investigator Name
Francois Ghiringhelli
Principal Investigator Email
fghiringhelli@cgfl.fr
Contact Person Name
Francois Ghiringhelli
Contact Person Email
fghiringhelli@cgfl.fr
Site Name
Centre Leon Berard
Department Name
Medical oncology
Principal Investigator Name
Isabelle RAY-COQUARD
Principal Investigator Email
Isabelle.ray-coquard@lyon.unicancer.fr
Contact Person Name
Isabelle RAY-COQUARD
Site Name
Institut Bergonie
Department Name
Medical Oncology
Principal Investigator Name
Coriolan Lebreton-Bourigault
Principal Investigator Email
c.lebreton@bordeaux.unicancer.fr
Contact Person Name
Coriolan Lebreton-Bourigault
Site Name
Centre Francois Baclesse
Department Name
Medical Oncology
Principal Investigator Name
Florence Joly
Principal Investigator Email
f.joly@baclesse.unicancer.fr
Contact Person Name
Florence Joly
Contact Person Email
f.joly@baclesse.unicancer.fr

Italy

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
09-07-2024
Processing Time Days
33
Number Of Sites
4
Number Of Participants
40

Sites

Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Gynecology Oncology Department
Principal Investigator Name
Nicoletta Colombo
Principal Investigator Email
Nicoletta.colombo@ieo.it
Contact Person Name
Nicoletta Colombo
Contact Person Email
Nicoletta.colombo@ieo.it
Site Name
Humanitas Mirasole S.p.A.
Department Name
Gynecologic Oncology
Principal Investigator Name
Domenica Lorusso
Principal Investigator Email
Domenica.lorusso@hunimed.eu
Contact Person Name
Domenica Lorusso
Contact Person Email
Domenica.lorusso@hunimed.eu
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Gynecological oncology
Principal Investigator Name
Sabrina Cecere
Principal Investigator Email
s.cecere@istitutotumori.na.it
Contact Person Name
Sabrina Cecere
Contact Person Email
s.cecere@istitutotumori.na.it
Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Gynecological Oncology
Principal Investigator Name
Vanda Salutari
Principal Investigator Email
Vanda.salutari@policlinicogemelli.it
Contact Person Name
Vanda Salutari

Spain

Earliest CTIS Part Ii Submission Date
06-06-2024
Latest Decision Or Authorization Date
28-06-2024
Processing Time Days
22
Number Of Sites
8
Number Of Participants
60

Sites

Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Oncology
Principal Investigator Name
Victor Moreno Garcia
Principal Investigator Email
Victor.Moreno@startmadrid.com
Contact Person Name
Victor Moreno Garcia
Contact Person Email
Victor.Moreno@startmadrid.com
Site Name
Complexo Hospitalario Universitario De Santiago
Department Name
Medical oncology
Principal Investigator Name
Alexandra Cortegoso
Contact Person Name
Alexandra Cortegoso
Site Name
Hospital Clinico San Carlos
Department Name
Medical Oncology
Principal Investigator Name
Antonio Casado Herraez
Principal Investigator Email
antoniocasado6@gmail.com
Contact Person Name
Antonio Casado Herraez
Contact Person Email
antoniocasado6@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Gynecological Oncology
Principal Investigator Name
Carmen García Durán
Principal Investigator Email
cgarciaduran@vhio.net
Contact Person Name
Carmen García Durán
Contact Person Email
cgarciaduran@vhio.net
Site Name
Clinica Universidad De Navarra
Department Name
Medical Oncology
Principal Investigator Name
Antonio Gonzalez Martin
Principal Investigator Email
agonzalezma@unav.es
Contact Person Name
Antonio Gonzalez Martin
Contact Person Email
agonzalezma@unav.es
Site Name
Institut Catala D'oncologia (Badalona)
Department Name
Medical Oncology
Principal Investigator Name
Maria Ochoa de Olza Amat
Principal Investigator Email
maochoa@iconcologia.net
Contact Person Name
Maria Ochoa de Olza Amat
Contact Person Email
maochoa@iconcologia.net
Site Name
Institut Catala D'oncologia (Girona)
Department Name
Oncology
Principal Investigator Name
Pilar Barretina
Principal Investigator Email
mpbarretina@iconcologia.net
Contact Person Name
Pilar Barretina
Contact Person Email
mpbarretina@iconcologia.net
Site Name
Complex additional Spanish site (listed)

Sponsor

Primary sponsor

Full Name
Regeneron Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Syneos Health Inc.
Responsibilities
Contract Research Organization, Pharmacovigilance Services
Name
Icon Clinical Research Limited
Responsibilities
Central Laboratory

Third parties

  • {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Contract Research Organization, Pharmacovigilance Services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"Interactive Voice Response System/ Interactive Web Response System","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Canada","full_name":"Cellcarta Biosciences Inc.","duties_or_roles":"Master Laboratory Services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ventana Medical Systems Inc.","duties_or_roles":"H&E Pathology review, PD-L1 and MUC16 analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"Central management of Image Data","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Andersonbrecon Inc.","duties_or_roles":"Investigational Product Distribution to Sites, Return and Destruction","organisation_type":"Pharmaceutical company"}
  • {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Central Laboratory","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
Ubamatamab
Active Substance
UBAMATAMAB
Modality
Bispecific antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
No marketing authorisation listed (investigational)
Investigational Product Name
Cemiplimab / LIBTAYO
Active Substance
CEMIPLIMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Marketing authorisation present for LIBTAYO (EU/1/19/1376/001) for cemiplimab (marketed product LIBTAYO); IMP variant used in study
Investigational Product Name
Sarilumab / Kevzara
Active Substance
SARILUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion / Subcutaneous injection (marketing product Kevzara listed as subcutaneous)
Route
Intravenous infusion / Subcutaneous injection
Authorisation Status
Kevzara marketing authorisation listed (EU/1/17/1196/013) for sarilumab; IMP variants used
Investigational Product Name
Tocilizumab
Active Substance
TOCILIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
No specific marketing authorisation number listed in product entry
Combination Treatment
Yes

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