Bintrafusp Alfa in High Mobility Group AT-Hook 2 (HMGA2) Expressing Triple Negative Breast Cancer

NCT04489940 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: MS200647_00202019-004833-18
• Study Type: interventional
• Target: 11
• Locations: 6 countries
• Sites: 45

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.

Conditions

Triple Negative Breast Neoplasms

Keywords

M7824; Bintrafusp alfa; Programmed death-ligand 1; Transforming growth factor-β (TGF-β); Breast Cancer; MS200647

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by an Independent Review Committee (IRC)

  The ORR was defined as the percentage of participants with a confirmed objective response of Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 as assessed by IRC. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.

  Time from first study intervention up to 321 days

Secondary Outcomes (12)

• Duration of Response (DOR) According to RECIST Version 1.1

  From first documented objective response to PD or death due to any cause, assessed up to 321 days

• Durable Response Rate (DRR) of at Least 6 Months Assessed by an Independent Review Committee (IRC)

  Time from first study intervention up to 321 days

• Progression-Free Survival (PFS) According to RECIST Version 1.1 Assessed by the IRC

  Time from first study intervention up to until the first documentation of PD or death, assessed up to 321 days

• Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by the Investigator

  From first documented objective response to PD or death due to any cause, assessed up to 321 days

• Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by the Investigator

  Time from first study intervention up to 321 days

Study Arms (1)

Bintrafusp alfa

EXPERIMENTAL

Drug: Bintrafusp alfa

Interventions

Bintrafusp alfa DRUG

Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

Also known as: M7824

Bintrafusp alfa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (45)

Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, Suite 3400

Newark, Delaware, 19713-2055, United States

Location

Mayo Clinic-Jacksonville

Jacksonville, Florida, 32224, United States

Location

Maryland Oncology Hematology, P.A.

Silver Spring, Maryland, 20904, United States

Location

New York Oncology Hematology, P.C. - Albany

Albany, New York, 12206, United States

Location

TheOhio State University, Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

Location

UPMC Hillman Cancer Center - Hillman Cancer Center

Monroeville, Pennsylvania, 15146, United States

Location

Charleston Hematology Oncology Associates, PA

Charleston, South Carolina, 29414, United States

Location

The West Clinic

Germantown, Tennessee, 38138, United States

Location

Texas Oncology, P.A. - Austin - Austin Central Cancer Center

Austin, Texas, 78731, United States

Location

Texas Oncology, P.A. - Medical City Dallas - Pediatric Hematology/Oncology

Dallas, Texas, 75230, United States

Location

Texas Oncology, P.A. - Plano

Plano, Texas, 75075, United States

Location

Texas Oncology-San Antonio Stone Oak

San Antonio, Texas, 78240, United States

Location

Texas Oncology, P.A. - Tyler

Tyler, Texas, 75702, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Virginia Oncology Associates - Hampton

Norfolk, Virginia, 23502, United States

Location

Universitair Ziekenhuis Brussel - Geriatrie

Brussels, Belgium

Location

UZ Leuven

Leuven, Belgium

Location

AZ Sint-Maarten - PARENT

Mechelen, Belgium

Location

Centre François Baclesse - Pathologies Gynecologiques

Caen, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital Privé du Confluent SAS

Nantes, France

Location

Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon - service d'oncologie medicale

Paris, France

Location

CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie

Plérin, France

Location

Institut Curie - Centre René Huguenin - Service d'Oncologie Médicale

Saint-Cloud, France

Location

IEO Istituto Europeo di Oncologia

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale - Dipartimento di Senologia

Napoli, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS - Oncologia Medica 2

Padua, Italy

Location

Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia II

Pisa, Italy

Location

Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica

Roma, Italy

Location

Istituto Clinico Humanitas

Rozzano, Italy

Location

SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary" - Chemotherapy

Arkhangelsk, Russia

Location

SBIH " Clinical Oncological Dispensary # 1" - Location

Krasnodar, Russia

Location

SBIH " Clinical Oncological Dispensary 1" - Location

Krasnodar, Russia

Location

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin" - Moscow Cancer Research Centre

Moscow, Russia

Location

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, Russia

Location

LLC "ClinicaUZI4D"

Pyatigorsk, Russia

Location

FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"

Saint Petersburg, Russia

Location

Tomsk Research Instutite of Oncology - Chemotherapy

Tomsk, Russia

Location

SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan

Ufa, Russia

Location

Hospital Universitario Reina Sofia - Dept of Oncology

Córdoba, Spain

Location

Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

Madrid, Spain

Location

Hospital Ruber Internacional - Servicio de Oncologia

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal - Servicio de Oncologia

Madrid, Spain

Location

Hospital Universitario Virgen del Rocio - Servicio de Oncologia

Seville, Spain

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

Based on sponsors decision for early termination of the study due to lack of probability to achieve interim data allowing expansion of this study. Hence, analysis for efficacy, or biomarker were not performed.

Results Point of Contact

• Title: Communication Center,
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49 6151725200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: July 28, 2020
• Study Start: October 12, 2020
• Primary Completion: January 27, 2022
• Study Completion: July 8, 2022
• Last Updated: April 10, 2023
• Results First Posted: April 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

IT (7); RU (9); ES (5); BE (3); US (15); FR (6)