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

Phase 2

Terminated

Conditions: Triple Negative Breast Neoplasms

Interventions: Drug: Bintrafusp alfa

Registration Number: NCT04489940

Lead Sponsor: EMD Serono Research & Development Institute, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 11

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bintrafusp alfa	Bintrafusp alfa	-

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by an Independent Review Committee (IRC)	Time from first study intervention up to 321 days	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Time from the first dose of study drug until occurrence of death due to any cause, assessed up to 321 days	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, and Adverse Events of Special Interest (AESIs)	Time from first study intervention up to 321 days	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.
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	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.
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	DRR was defined as the number of participants having a DOR of at least 6 months, out of the total number of participants.
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	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.
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	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.
Durable Response Rate (DRR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator	Time from first study intervention up to 321 days	DRR was defined as the number of participants having a DOR of at least 6 months, out of the total number of participants.
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	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.
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa	Pre-dose, End of Infusion from Day 1 to 321	Ceoi was the serum concentration observed immediately at the end of infusion. This was taken directly from the observed bintrafusp alfa concentration-time data.
Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa	Pre-dose, End of Infusion from Day 1 to 321	Ctrough was the serum concentration observed immediately before next dosing.
Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa	Pre-dose, End of Infusion from Day 1 to 321	The detection of antibodies to bintrafusp alfa was performed using a validated ADA assay method with tiered testing of screening, confirmatory and titration.
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator	Time from first study intervention up to the first documentation of PD or death, assessed up to 321 days	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.

Trial Locations

Locations (45): Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, Suite 3400
🇺🇸
Newark, Delaware, United States
Mayo Clinic-Jacksonville
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Jacksonville, Florida, United States
Maryland Oncology Hematology, P.A.
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Silver Spring, Maryland, United States
New York Oncology Hematology, P.C. - Albany
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Albany, New York, United States
TheOhio State University, Stefanie Spielman Comprehensive Breast Center
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Columbus, Ohio, United States
UPMC Hillman Cancer Center - Hillman Cancer Center
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Monroeville, Pennsylvania, United States
Charleston Hematology Oncology Associates, PA
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Charleston, South Carolina, United States
The West Clinic
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Germantown, Tennessee, United States
Texas Oncology, P.A. - Austin - Austin Central Cancer Center
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Austin, Texas, United States
Texas Oncology, P.A. - Medical City Dallas - Pediatric Hematology/Oncology
🇺🇸
Dallas, Texas, United States
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Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, Suite 3400
🇺🇸Newark, Delaware, United States