Bintrafusp Alfa in High Mobility Group AT-Hook 2 (HMGA2) Expressing Triple Negative Breast Cancer
- Registration Number
- NCT04489940
- 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
- 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
- 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)
UZ Leuven
🇧🇪Leuven, Belgium
Medical Oncology Hematology Consultants, PA, Helen F. Graham Cancer Center, Suite 3400
🇺🇸Newark, Delaware, United States
Mayo Clinic-Jacksonville
🇺🇸Jacksonville, Florida, United States
Maryland Oncology Hematology, P.A.
🇺🇸Silver Spring, Maryland, United States
New York Oncology Hematology, P.C. - Albany
🇺🇸Albany, New York, United States
TheOhio State University, Stefanie Spielman Comprehensive Breast Center
🇺🇸Columbus, Ohio, United States
UPMC Hillman Cancer Center - Hillman Cancer Center
🇺🇸Monroeville, Pennsylvania, United States
Charleston Hematology Oncology Associates, PA
🇺🇸Charleston, South Carolina, United States
Texas Oncology, P.A. - Austin - Austin Central Cancer Center
🇺🇸Austin, Texas, United States
The West Clinic
🇺🇸Germantown, Tennessee, United States
Texas Oncology, P.A. - Medical City Dallas - Pediatric Hematology/Oncology
🇺🇸Dallas, Texas, United States
Texas Oncology, P.A. - Tyler
🇺🇸Tyler, Texas, United States
Texas Oncology, P.A. - Plano
🇺🇸Plano, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates - Hampton
🇺🇸Norfolk, Virginia, United States
Universitair Ziekenhuis Brussel - Geriatrie
🇧🇪Brussel, Belgium
AZ Sint-Maarten - PARENT
🇧🇪Mechelen, Belgium
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, France
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, Russian Federation
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, Spain
Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica
🇮🇹Roma, 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
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Texas Oncology-San Antonio Stone Oak
🇺🇸San Antonio, Texas, United States