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

A Phase II, Multicenter, Open Label Study of Bintrafusp Alfa (M7824) Monotherapy in Participants With HMGA2-expressing Triple Negative Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Triple Negative Breast Neoplasms
• Intervention / Treatment: Drug: Bintrafusp alfa

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium
    • Universitair Ziekenhuis Brussel - Geriatrie
  • Leuven, Belgium
    • UZ Leuven
  • Mechelen, Belgium
    • AZ Sint-Maarten - PARENT
• France
  • Caen Cedex 05, France
    • Centre François Baclesse - Pathologies Gynecologiques
  • Lyon, France
    • Centre Leon Berard
  • Nantes cedex 2, France
    • Hôpital privé du Confluent SAS
  • Paris, France
    • Groupe Hospitalier Diaconesses - Hôpital De La Croix Saint Simon - service d'oncologie medicale
  • Plérin, France
    • CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
  • Saint-cloud, France
    • Institut Curie - Centre René Huguenin - Service d'Oncologie Médicale
• Italy
  • Milano, Italy
    • Ospedale San Raffaele
  • Milano, Italy
    • Ieo Istituto Europeo Di Oncologia
  • Napoli, Italy
    • Istituto Nazionale Tumori Fondazione G. Pascale - Dipartimento di Senologia
  • Padova, Italy
    • IOV - Istituto Oncologico Veneto IRCCS - Oncologia Medica 2
  • Pisa, Italy
    • Azienda Ospedaliero Universitaria Pisana - U.O. Oncologia II
  • Roma, Italy
    • Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica
  • Rozzano, Italy
    • Istituto Clinico Humanitas
• Russian Federation
  • Arkhangelsk, Russian Federation
    • SBIH of Arkhangelsk region "Arkhangelsk Clinical Oncological Dispensary" - Chemotherapy
  • Krasnodar, Russian Federation
    • SBIH " Clinical Oncological Dispensary # 1" - Location
  • Krasnodar, Russian Federation
    • SBIH " Clinical Oncological Dispensary 1" - Location
  • Moscow, Russian Federation
    • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin" - Moscow Cancer Research Centre
  • Omsk, Russian Federation
    • BHI of Omsk region "Clinical oncology dispensary"
  • Pyatigorsk, Russian Federation
    • LLC "ClinicaUZI4D"
  • Saint Petersburg, Russian Federation
    • FSBI "Clinical Research and Practical Center for specialized medical care (oncology)"
  • Tomsk, Russian Federation
    • Tomsk Research Instutite of Oncology - Chemotherapy
  • Ufa, Russian Federation
    • SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
• Spain
  • Cordoba, Spain
    • Hospital Universitario Reina Sofia - Dept of Oncology
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
  • Madrid, Spain
    • Hospital Ruber Internacional - Servicio de Oncologia
  • Madrid, Spain
    • Hospital Universitario Ramon y Cajal - Servicio de Oncologia
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio - Servicio de Oncologia
• United States
  • Delaware
    • Newark, Delaware, United States, 19713-2055
      • Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, Suite 3400
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic-Jacksonville
  • Maryland
    • Silver Spring, Maryland, United States, 20904
      • Maryland Oncology Hematology, P.A.
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology, P.C. - Albany
  • Ohio
    • Columbus, Ohio, United States, 43212
      • TheOhio State University, Stefanie Spielman Comprehensive Breast Center
  • Pennsylvania
    • Monroeville, Pennsylvania, United States, 15146
      • UPMC Hillman Cancer Center - Hillman Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates, PA
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • The West Clinic
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology, P.A. - Austin - Austin Central Cancer Center
    • Dallas, Texas, United States, 75230
      • Texas Oncology, P.A. - Medical City Dallas - Pediatric Hematology/Oncology
    • Plano, Texas, United States, 75075
      • Texas Oncology, P.A. - Plano
    • San Antonio, Texas, United States, 78240
      • Texas Oncology-San Antonio Stone Oak
    • Tyler, Texas, United States, 75702
      • Texas Oncology, P.A. - Tyler
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates - Hampton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bintrafusp alfa	Drug: Bintrafusp alfa; 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.; Other Names: M7824

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) According to RECIST Version 1.1	DOR was defined for participants with a confirmed objective response as the time from first documentation of a confirmed objective response (CR or PR) according to RECIST 1.1 to the date of first documentation of objective PD or death due to any cause, whichever occurs first. 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. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC.	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)	DRR was defined as the number of participants having a DOR of at least 6 months, out of the total number of participants.	Time from first study intervention up to 321 days
Progression-Free Survival (PFS) According to RECIST Version 1.1 Assessed by the IRC	PFS was defined as the time from first study intervention until the first documentation of PD or death due to any cause in the absence of documented PD, whichever occurred first. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The tumor response was determined according to RECIST version 1.1 and 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	DOR was defined for participants with a confirmed objective response as the time from first documentation of a confirmed objective response (CR or PR) according to RECIST 1.1 to the date of first documentation of objective PD or death due to any cause, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in sum of longest diameter (SLD) of all lesions. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by 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	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 investigator. 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
Durable Response Rate (DRR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator	DRR was defined as the number of participants having a DOR of at least 6 months, out of the total number of participants.	Time from first study intervention up to 321 days
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator	PFS was defined as the time from first study intervention until the first documentation of PD or death due to any cause in the absence of documented PD, whichever occurred first. PD: At least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. The tumor response was determined according to RECIST version 1.1 and assessed by the investigator.	Time from first study intervention up to the first documentation of PD or death, assessed up to 321 days
Overall Survival (OS)	OS was defined as the time from first day of study treatment to death due to any cause. Participants without documented death at the time of analysis are censored at the date of the last follow-up. OS was summarized by Kaplan-Meier (KM) methods.	Time from the first dose of study drug until occurrence of death due to any cause, assessed up to 321 days
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, and Adverse Events of Special Interest (AESIs)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. The AESIs considered in this study are infusion-related reactions including immediate hypersensitivity, immune-related adverse events, skin adverse events, bleeding events and anemia.	Time from first study intervention up to 321 days
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa	Ceoi was the serum concentration observed immediately at the end of infusion. This was taken directly from the observed bintrafusp alfa concentration-time data.	Pre-dose, End of Infusion from Day 1 to 321
Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa	Ctrough was the serum concentration observed immediately before next dosing.	Pre-dose, End of Infusion from Day 1 to 321
Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa	The detection of antibodies to bintrafusp alfa was performed using a validated ADA assay method with tiered testing of screening, confirmatory and titration.	Pre-dose, End of Infusion from Day 1 to 321

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2020
• Primary Completion (Actual): January 27, 2022
• Study Completion (Actual): July 8, 2022

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; M7824; Bintrafusp alfa; Programmed death-ligand 1; Transforming growth factor-β (TGF-β); MS200647
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: MS200647_0020; 2019-004833-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing 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
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No