Clinical trial NCT04489940: Bintrafusp Alfa in High Mobility Group AT-Hook 2 (HMGA2) Expressing Triple Negative Breast Cancer
Official title: A Phase II, Multicenter, Open Label Study of Bintrafusp Alfa (M7824) Monotherapy in Participants With HMGA2-expressing Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Triple Negative Breast Neoplasms
Keywords: M7824
Bintrafusp alfa
Programmed death-ligand 1
Transforming growth factor-β (TGF-β)
Breast Cancer
MS200647
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
First posted: 2020-07-28
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study was to evaluate bintrafusp alfa monotherapy in participants with triple negative breast cancer (TNBC) who express high levels of HMGA2 as determined by a centralized reverse transcriptase-polymerase chain reaction (RT-PCR) test.


Eligibility criteria: Inclusion Criteria:

* Study participants have histologically or cytologically confirmed TNBC
* Absence of human epidermal growth factor receptor 2 (HER2), estrogen receptor, and progesterone receptor expression must be documented (criteria for defining TNBC are outlined in the protocol)
* Participants must have received at least one line of systemic therapy for metastatic disease and have progressed on the line of therapy immediately prior to study entry. There is no limit to the number of prior therapies
* Participants may prescreen for HMGA2 expression while on preceding treatment, however screening should only occur if in the opinion of the Investigator, the participant would likely be eligible for study within 6 months
* Participants must have measurable disease
* Availability of either archival tumor tissue or fresh core or excisional biopsy of a tumor lesion (primary or metastatic, excluding bone biopsies) is mandatory to determine HMGA2 expression level prior to enrollment
* HMGA2 high tumor expression is required and will be determined by a central lab
* Participants who have Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1
* Participants have a life expectancy greater than or equal to (\>=) 12 weeks as judged by the Investigator at study start
* Participants have adequate hematological, hepatic and renal and coagulation function as defined in the protocol
* Participants with known Human Immunodeficiency Virus (HIV) infections are in general eligible if the criteria as defined in the protocol are met (Food and Drug Administration \[FDA\] Guidance on Cancer Clinical Trial Eligibility, March 2019)
* Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections are in general eligible if the criteria as defined in the protocol are met (FDA Guidance on Cancer Clinical Trial Eligibility, March 2019)
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participants with active central nervous system (CNS) metastases causing clinical symptoms or metastases that require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 4 weeks, and are not using steroids for at least 7 days prior to the start of study intervention
* Participants must not have received prior cancer treatment with any other immunotherapy or checkpoint inhibitors, or any other immune-modulating monoclonal antibody
* Participants that received any organ transplantation, including stem-cell transplantation, but with the exception of transplants that do not require immunosuppression
* Participants with significant acute or chronic infections
* Participants with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by an Independent Review Committee (IRC)
timeFrame: Time from first study intervention up to 321 days
Secondary outcomes:
measure: Duration of Response (DOR) According to RECIST Version 1.1
timeFrame: From first documented objective response to PD or death due to any cause, assessed up to 321 days
measure: Durable Response Rate (DRR) of at Least 6 Months Assessed by an Independent Review Committee (IRC)
timeFrame: Time from first study intervention up to 321 days
measure: Progression-Free Survival (PFS) According to RECIST Version 1.1 Assessed by the IRC
timeFrame: Time from first study intervention up to until the first documentation of PD or death, assessed up to 321 days
measure: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by the Investigator
timeFrame: From first documented objective response to PD or death due to any cause, assessed up to 321 days
measure: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by the Investigator
timeFrame: Time from first study intervention up to 321 days
measure: Durable Response Rate (DRR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
timeFrame: Time from first study intervention up to 321 days
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
timeFrame: Time from first study intervention up to the first documentation of PD or death, assessed up to 321 days
measure: Overall Survival (OS)
timeFrame: Time from the first dose of study drug until occurrence of death due to any cause, assessed up to 321 days
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, and Adverse Events of Special Interest (AESIs)
timeFrame: Time from first study intervention up to 321 days
measure: Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa
timeFrame: Pre-dose, End of Infusion from Day 1 to 321
measure: Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa
timeFrame: Pre-dose, End of Infusion from Day 1 to 321
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa
timeFrame: Pre-dose, End of Infusion from Day 1 to 321
Other outcomes:
Locations:
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, Suite 3400
state: Delaware
city: Jacksonville
country: United States
facility: Mayo Clinic-Jacksonville
state: Florida
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Albany
country: United States
facility: New York Oncology Hematology, P.C. - Albany
state: New York
city: Columbus
country: United States
facility: TheOhio State University, Stefanie Spielman Comprehensive Breast Center
state: Ohio
city: Monroeville
country: United States
facility: UPMC Hillman Cancer Center - Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology Oncology Associates, PA
state: South Carolina
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology, P.A. - Austin - Austin Central Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, P.A. - Medical City Dallas - Pediatric Hematology/Oncology
state: Texas
city: Plano
country: United States
facility: Texas Oncology, P.A. - Plano
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Stone Oak
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Tyler
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - Hampton
state: Virginia
city: Brussel
country: Belgium
facility: Universitair Ziekenhuis Brussel - Geriatrie
city: Leuven
country: Belgium
facility: UZ Leuven
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten - PARENT
city: Caen Cedex 05
country: France
facility: Centre François Baclesse - Pathologies Gynecologiques
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nantes cedex 2
country: France
facility: Hôpital Privé du Confluent SAS
city: Paris
country: France
facility: Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon - service d'oncologie medicale
city: Plérin
country: France
facility: CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
city: Saint-cloud
country: France
facility: Institut Curie - Centre René Huguenin - Service d'Oncologie Médicale
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale - Dipartimento di Senologia
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS - Oncologia Medica 2
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia II
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Arkhangelsk
country: Russian Federation
facility: SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary" - Chemotherapy
city: Krasnodar
country: Russian Federation
facility: SBIH " Clinical Oncological Dispensary # 1" - Location
city: Krasnodar
country: Russian Federation
facility: SBIH " Clinical Oncological Dispensary 1" - Location
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin" - Moscow Cancer Research Centre
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: Pyatigorsk
country: Russian Federation
facility: LLC "ClinicaUZI4D"
city: Saint Petersburg
country: Russian Federation
facility: FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"
city: Tomsk
country: Russian Federation
facility: Tomsk Research Instutite of Oncology - Chemotherapy
city: Ufa
country: Russian Federation
facility: SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia - Dept of Oncology
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Hospital Ruber Internacional - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal - Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - Servicio de Oncologia
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: