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

Triple Negative Breast Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04489940
• Other study ID #: MS200647_0020
• Secondary ID: 2019-004833-18
• Status: Terminated
• Phase: Phase 2
• Start date: October 12, 2020
• Est. completion date: July 8, 2022

Study information

• Verified date: March 2023
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 11
• Est. completion date: July 8, 2022
• Est. primary completion date: January 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

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.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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