Trial Outcomes & Findings for Bintrafusp Alfa in High Mobility Group AT-Hook 2 (HMGA2) Expressing Triple Negative Breast Cancer (NCT NCT04489940)
NCT ID: NCT04489940
Last Updated: 2023-04-10
Results Overview
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.
TERMINATED
PHASE2
11 participants
Time from first study intervention up to 321 days
2023-04-10
Participant Flow
A total of 15 participants were screened, of which 11 participants received bintrafusp alfa monotherapy.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
COMPLETED
|
1
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Other
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Death
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Bintrafusp Alfa in High Mobility Group AT-Hook 2 (HMGA2) Expressing Triple Negative Breast Cancer
Baseline characteristics by cohort
| Measure |
Bintrafusp Alfa
n=11 Participants
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.
|
|---|---|
|
Age, Continuous
|
59 Years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Time from first study intervention up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first documented objective response to PD or death due to any cause, assessed up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first study intervention up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
DRR was defined as the number of participants having a DOR of at least 6 months, out of the total number of participants.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first study intervention up to until the first documentation of PD or death, assessed up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first documented objective response to PD or death due to any cause, assessed up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first study intervention up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first study intervention up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
DRR was defined as the number of participants having a DOR of at least 6 months, out of the total number of participants.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first study intervention up to the first documentation of PD or death, assessed up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from the first dose of study drug until occurrence of death due to any cause, assessed up to 321 daysPopulation: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Time from first study intervention up to 321 daysPopulation: The Safety Analysis Set (SAF) analysis set included all participants who received at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Bintrafusp Alfa
n=11 Participants
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.
|
|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, and Adverse Events of Special Interest (AESIs)
Participants with TEAEs
|
10 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, and Adverse Events of Special Interest (AESIs)
Participants with Treatment-Related TEAEs
|
5 Count of Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related AEs, and Adverse Events of Special Interest (AESIs)
Participants with AESIs
|
4 Count of Participants
|
SECONDARY outcome
Timeframe: Pre-dose, End of Infusion from Day 1 to 321Population: As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Ceoi was the serum concentration observed immediately at the end of infusion. This was taken directly from the observed bintrafusp alfa concentration-time data.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, End of Infusion from Day 1 to 321Population: As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
Ctrough was the serum concentration observed immediately before next dosing.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-dose, End of Infusion from Day 1 to 321Population: As per changes in planned analysis, the outcome measure related to pharmacokinetics were not assessed.
The detection of antibodies to bintrafusp alfa was performed using a validated ADA assay method with tiered testing of screening, confirmatory and titration.
Outcome measures
Outcome data not reported
Adverse Events
Bintrafusp Alfa
Serious adverse events
| Measure |
Bintrafusp Alfa
n=11 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
General disorders
Disease progression
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
General disorders
General physical health deterioration
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
General disorders
Pain
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Infections and infestations
COVID-19 pneumonia
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Infections and infestations
Gastroenteritis
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Nervous system disorders
Epilepsy
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Nervous system disorders
Haemorrhagic stroke
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
Other adverse events
| Measure |
Bintrafusp Alfa
n=11 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
27.3%
3/11 • Time from first study intervention up to 321 days.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Ear and labyrinth disorders
Ear pruritus
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Abdominal distension
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Abdominal pain
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Constipation
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
27.3%
3/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Gastritis
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Gingival bleeding
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Nausea
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Stomatitis
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
Gastrointestinal disorders
Vomiting
|
27.3%
3/11 • Time from first study intervention up to 321 days.
|
|
General disorders
Asthenia
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
General disorders
Fatigue
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
General disorders
Pyrexia
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Infections and infestations
Diverticulitis
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Infections and infestations
Oral candidiasis
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Infections and infestations
Urinary tract infection
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Infections and infestations
Vaginal infection
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Injury, poisoning and procedural complications
Fall
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Alanine aminotransferase increased
|
27.3%
3/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Amylase increased
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Aspartate aminotransferase increased
|
27.3%
3/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Blood alkaline phosphatase increased
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Blood creatine phosphokinase increase
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Blood lactate dehydrogenase increased
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Blood phosphorus increased
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Blood thyroid stimulating hormone dec
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Blood urea increased
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
C-reactive protein increased
|
27.3%
3/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Investigations
Thyroxine free increased
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Nervous system disorders
Headache
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
Nervous system disorders
Neuropathy peripheral
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Psychiatric disorders
Insomnia
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
Skin and subcutaneous tissue disorders
Rash
|
18.2%
2/11 • Time from first study intervention up to 321 days.
|
|
Vascular disorders
Hypertension
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
|
Infections and infestations
Respiratory tract infection viral
|
9.1%
1/11 • Time from first study intervention up to 321 days.
|
Additional Information
Communication Center,
Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place