This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Bintrafusp Alfa in High Mobility Group AT-Hook 2 (HMGA2) Expressing Triple Negative Breast Cancer (NCT04489940), a na phase 2 study. The primary outcome is Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by an Independent Review Committee (IRC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04489940 |
| Phase | Phase 2 |
| Condition | Triple Negative Breast Neoplasms |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 11 |
| Arms in the primary outcome | n/a |
| Lead sponsor | EMD Serono Research & Development Institute, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants with triple negative breast cancer whose tumors expressed high levels of HMGA2, as determined by a centralized reverse transcriptase-polymerase chain reaction test. The registry record lists 11 participants enrolled. Further eligibility details and participant characteristics are not reported in the registry record.
Intervention
Bintrafusp alfa given as monotherapy. The registry record identifies the intervention as a drug but does not report the dose, schedule, route, or treatment duration.
Comparator
There was no comparison group. The study is listed as a single-group study, with allocation recorded as not applicable and masking as none. It was not a randomized comparison.
Primary question
The planned primary outcome was the objective response rate assessed by an independent review committee using RECIST version 1.1. It was intended to measure the percentage of participants with a confirmed complete or partial response. The registry record states that the efficacy outcome measures were not assessed following changes in planned analysis.
3. Trial Design
This was a phase II, multicenter, open-label, single-group study of bintrafusp alfa monotherapy in participants with HMGA2-expressing triple negative breast cancer. The registry lists 11 participants as enrolled. Because there was no control arm and the study was not randomized, its design does not provide a concurrent treatment comparison.
The study began on 2020-10-12, and its primary completion date is listed as 2022-01-27. Its status is terminated. The reason for termination is not reported in the registry record. The planned primary outcome covered the time from first study intervention up to 321 days and was objective response rate assessed by an independent review committee according to RECIST version 1.1.
The study summary describes the target population as participants with triple negative breast cancer who had high HMGA2 expression determined by a centralized reverse transcriptase-polymerase chain reaction test. Other eligibility criteria, participant demographics, the treatment schedule, and the number of participants who received treatment are not reported in the registry record. The registry lists eight secondary outcome descriptions, including response duration, durable response rate, progression-free survival, and overall survival, with some assessed by an independent review committee and others by the investigator.
The registry record says that, following changes in planned analysis, the efficacy outcome measures were not assessed. It therefore does not provide an efficacy result for the planned primary endpoint. The fact that the study enrolled participants and has a listed primary completion date does not establish that the planned efficacy analyses were completed.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: A total of 15 participants were screened, of which 11 participants received bintrafusp alfa monotherapy.
Overall Study
| Stage | Bintrafusp Alfa |
|---|---|
| STARTED | 11 |
| COMPLETED | 1 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Bintrafusp Alfa |
|---|---|
| Other | 2 |
| Withdrawal by Subject | 2 |
| Death | 5 |
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: As per changes in planned analysis, the outcome measure related to efficacy were not assessed.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: The Full analysis set (FAS) included all participants, who were administered at least one infusion of bintrafusp alfa.
| Characteristic | Unit | Bintrafusp Alfa |
|---|---|---|
| Participants analysed | 11 | |
| Age, Continuous | Years | 59 (SD 11.3) |
| Sex: Female, Male: Female | Participants | 11 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 9 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by an Independent Review Committee (IRC), measured over Time from first study intervention up to 321 days.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The planned primary endpoint was objective response rate, or ORR, according to RECIST version 1.1, assessed by an independent review committee. ORR is the percentage of participants with a confirmed complete response or partial response. In the registry description, complete response means disappearance of all evidence of target and non-target lesions. Partial response means at least 30 percent (%) reduction from baseline in the sum of the longest diameters of all lesions.
As a general statistical concept, ORR reduces a set of tumor assessments to the proportion of participants who meet a defined response criterion during the specified assessment period. It can describe observed tumor shrinkage without, by itself, measuring how long a response lasts or how outcomes compare with another treatment. That is why the registry also lists separate outcomes for duration of response and other measures.
Use of an independent review committee provides an assessment distinct from the investigator’s assessment, according to the endpoint description. However, the registry record does not report the committee’s findings or an ORR estimate. It states that efficacy outcomes were not assessed after changes in planned analysis. The reason for the analysis change and any details about assessment procedures beyond those in the endpoint description are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive point is that the registry record does not report an efficacy result for the planned primary endpoint. Although the primary outcome is defined as the proportion of participants with a confirmed complete or partial response, the record states that efficacy outcome measures were not assessed following changes in planned analysis. There is therefore no posted ORR estimate to interpret as evidence for or against a response in this study.
The record lists 11 participants enrolled in a single-group study. That enrollment figure describes the study’s recorded size; it is not an efficacy denominator. The registry does not report how many participants received treatment, had evaluable tumor assessments, or were included in an analysis population. Without those details and the number of confirmed responses, an ORR cannot be reconstructed from the registry information.
The study’s open-label, single-group design also matters when interpreting any outcome that might have been reported. Without a control group, observed outcomes would not establish how results compare with another treatment or with outcomes under a different care strategy. The independent review committee was named for the planned primary assessment, but its results are not reported in the registry record.
The registry lists secondary outcomes such as duration of response, durable response rate, progression-free survival, and overall survival. Their presence as planned outcomes is not evidence that results were collected or analyzed. The record reports no analyses and does not provide numerical efficacy findings for these outcomes. It also does not describe the reason efficacy measures were not assessed.
Consequently, this record supports a description of the study’s question, design, status, and posted safety figures, but it does not support a conclusion about the primary efficacy outcome. Lack of a posted efficacy estimate is not the same as an estimate showing no response, and it is not evidence that the treatment was effective. The amount of uncertainty around efficacy cannot be quantified from a missing result. Any claims about response, treatment benefit, or lack of benefit would go beyond what the registry record reports.
For the same reason, planning illustrations based on an observed effect should not be read as trial findings or as observed power. The registry record does not report an efficacy effect estimate from which to assess precision. The reported status is terminated, but the reason for termination is not reported in the registry record. These points limit what can be learned about efficacy from the posted information.
9. Statistical Methods Explained
The planned primary outcome is a proportion: the number of participants meeting the confirmed response definition divided by the relevant analysis population. The endpoint description specifies that response was to be assessed under RECIST version 1.1 by an independent review committee. It defines complete and partial response, but it does not report a numerator, a denominator, or a calculated percentage. The record explicitly states that efficacy outcomes were not assessed following changes in planned analysis.
What does an objective response rate represent?
As a general statistical explanation, a response rate is a binary-outcome summary: each participant either meets the response definition or does not, within the specified assessment rules. The resulting proportion gives a compact description of how often the defined response was observed in the analyzed group. Its meaning depends on a clear response definition, a defined analysis population, and adequate follow-up and assessment. The endpoint description supplies the response criteria and an assessment period, but the analyzed population and response findings are not reported in the registry record.
A proportion is also subject to sampling uncertainty. As a general concept, a confidence interval expresses a range of values compatible with the observed data under a stated statistical method. A narrow interval generally indicates greater precision than a wide interval, while neither interval nor point estimate alone resolves limitations such as the absence of a control group. No ORR estimate or confidence interval is reported in the registry record, so the precision of the planned efficacy result cannot be evaluated.
Why distinguish the reviewer from the investigator?
The primary endpoint names an independent review committee, while several secondary outcomes name investigator assessments. As a general methodological matter, separate assessors can produce distinct evaluations of the same clinical measurements. The registry’s designation tells the reader who was to assess the endpoint, but it does not establish that assessments were performed or provide a comparison between assessors. No such results are reported in the registry record.
What can a single-group design estimate?
In general, a single-group study can describe outcomes among participants receiving the intervention, if those outcomes are measured and analyzed. It does not include a concurrent control group for estimating a between-group treatment contrast. This study is listed as single-group, with allocation not applicable and masking none. No randomized comparison can therefore be inferred from its design. Open-label status means masking is not part of the listed design; it does not, on its own, establish how any assessment might have been affected.
Several registry-listed outcomes involve time, including duration of response, progression-free survival, and overall survival. As a general concept, time-to-event analyses address both when an event occurs and the possibility that some participants have not experienced the event by the end of observation. Their interpretation depends on event definitions, follow-up, censoring rules, and analysis populations. Those details and numerical analyses are not reported in the registry record. The registry lists these outcomes but does not provide results for them.
How should planning illustrations be understood?
The planning assumptions describe an illustration based on a stated fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The assumptions distinguish participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes. As a general explanation, such an illustration asks what sample size might be needed under chosen assumptions; it is not a report of the trial’s actual design or enrollment target. The stated assumptions are not evidence that this single-group study planned a two-arm comparison.
Sample-size illustrations are planning calculations, not observed power and not outcome evidence. Their interpretation depends on the assumed effect and analysis framework. The registry record does not report a trial-specific sample-size justification, and it does not report an efficacy result for the primary endpoint. Any planning illustration should therefore be kept separate from the study’s observed findings. It cannot fill in the missing efficacy analysis or establish that the study was designed around the illustration’s assumptions.
The registry reports zero analyses. The statistical analysis plan, including methods for handling missing observations, multiplicity, and analysis populations, is not reported in the registry record. Those absences matter because they prevent readers from checking how planned outcomes were translated into analyses or how uncertainty and incomplete follow-up were handled.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures overall and names several secondary outcomes, including response duration, durable response rate, progression-free survival, and overall survival. Multiple outcomes can raise a multiplicity question: as a general statistical concept, examining several outcomes can increase the chance of finding a seemingly notable result by chance if the analyses are treated as independent confirmatory tests. A prespecified testing hierarchy or adjustment can address that issue, but the multiplicity strategy is not reported in the registry record.
The record reports zero analyses and states that efficacy outcome measures were not assessed following changes in planned analysis. The nature and timing of those changes, whether any analyses were conducted outside the posted record, and whether the primary or secondary endpoints were revised are not reported in the registry record. No efficacy estimates are available to evaluate.
Missing-data methods and analysis populations are also not reported in the registry record. In particular, it does not identify the number treated, the number with evaluable assessments, the population used for each outcome, or how missing assessments or incomplete follow-up were handled. These are important details for interpreting a response percentage or a time-to-event analysis. The enrolled count alone cannot establish the denominator for an efficacy analysis.
The record’s statement that efficacy outcomes were not assessed should not be interpreted as a zero response rate or as an analysis showing no effect. It means that the posted registry information does not provide those efficacy results. The reason for not assessing them and the consequences for any planned statistical testing are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Bintrafusp Alfa | 7 | 11 | 63.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Bintrafusp Alfa | 6 of 11 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bintrafusp Alfa | 9 of 11 |
Most frequent serious adverse event terms
| Event term | Organ system | Bintrafusp Alfa |
|---|---|---|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 11 |
| Disease progression | General disorders | 1 of 11 |
| General physical health deterioration | General disorders | 1 of 11 |
| Pain | General disorders | 1 of 11 |
| COVID-19 pneumonia | Infections and infestations | 1 of 11 |
| Gastroenteritis | Infections and infestations | 1 of 11 |
| Epilepsy | Nervous system disorders | 1 of 11 |
| Haemorrhagic stroke | Nervous system disorders | 1 of 11 |
| Vaginal haemorrhage | Reproductive system and breast disorders | 1 of 11 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bintrafusp Alfa |
|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 3 of 11 |
| Diarrhoea | Gastrointestinal disorders | 3 of 11 |
| Vomiting | Gastrointestinal disorders | 3 of 11 |
| Alanine aminotransferase increased | Investigations | 3 of 11 |
| Aspartate aminotransferase increased | Investigations | 3 of 11 |
| C-reactive protein increased | Investigations | 3 of 11 |
| Gingival bleeding | Gastrointestinal disorders | 2 of 11 |
| Stomatitis | Gastrointestinal disorders | 2 of 11 |
| Asthenia | General disorders | 2 of 11 |
| Blood alkaline phosphatase increased | Investigations | 2 of 11 |
Serious events with the highest arm-level rate: gastrointestinal haemorrhage (9.1%), disease progression (9.1%), general physical health deterioration (9.1%), pain (9.1%), covid-19 pneumonia (9.1%).
The posted safety figures list 11 participants at risk in the bintrafusp alfa group. Seven participants are listed as affected by at least one serious adverse event, and nine are listed as affected by other adverse events. The record also lists six deaths. These are descriptive counts; they do not establish that the intervention caused an event or a death.
The serious-event terms listed at 9.1% each are gastrointestinal haemorrhage, disease progression, general physical health deterioration, pain, COVID-19 pneumonia, and gastroenteritis. The registry record does not provide further context for these terms in the figures described, such as timing, severity details beyond the serious-event classification, recurrence, or attribution. The listed percentages should be read as posted, not as evidence of a causal relationship.
As a general safety interpretation, event counts in a single group describe what was recorded among participants at risk; they do not provide a comparison with an untreated or alternative-treatment group. The registry record does not report the causes of the six deaths or whether any were considered related to treatment. The study’s terminated status does not, by itself, explain the safety figures or establish why the study ended.
12. What the Result Does, and Does Not, Mean
The registry record documents a phase II, open-label, single-group study of bintrafusp alfa monotherapy in participants with HMGA2-expressing triple negative breast cancer. It also documents that 11 participants were enrolled, that the study is terminated, and that efficacy outcome measures were not assessed following changes in planned analysis. Those details describe the record; they do not provide a measured primary efficacy outcome.
The planned endpoint would have summarized the proportion of participants with a confirmed complete or partial response under RECIST version 1.1, as assessed by an independent review committee. Because no estimate, response count, or analysis population is reported, readers cannot determine the observed response rate or how precisely it might have been estimated. The registry record therefore supports neither a conclusion of efficacy nor a conclusion of no efficacy.
The listed safety counts describe adverse events and deaths recorded in the bintrafusp alfa group. Without a control group, these counts cannot show how the observed safety experience compares with another intervention. The registry record does not report whether events or deaths were considered related to treatment, and the listed counts should not be taken as causal effects.
More broadly, the design does not support a randomized treatment comparison. The registry lists secondary efficacy outcomes, but does not report their analyses. It also does not report the reason for termination, the reason for the planned-analysis changes, or the methods for handling missing data and defining analysis populations. These gaps constrain interpretation of both efficacy and the context of the posted safety information.
The most accurate conclusion is limited: the registry records a study and its planned outcomes, but does not post the planned efficacy assessments. That missing information is distinct from a negative finding. It leaves the central efficacy question unanswered by the registry record.
13. Why This Trial Matters Statistically
This study is statistically notable because its planned primary question and its posted record do not align as a complete efficacy analysis. The registry defines an objective response endpoint, identifies the assessment criteria and reviewer, and specifies an assessment period. It then states that efficacy outcome measures were not assessed following changes in planned analysis. Readers therefore have a defined question but no reported estimate with which to answer it.
The design also illustrates the limits of single-group evidence. In general, outcomes in one group can describe what was observed in that group, but do not by themselves estimate a contrast against another treatment. This study is listed as single-group, open-label, and not randomized. Even if its planned response rate had been reported, it would not constitute a randomized comparison of treatments.
The record is also a reminder to distinguish planned outcomes from analyzed outcomes. Response rate, response duration, durable response, progression-free survival, and overall survival appear among the listed outcomes, but their listing does not establish that results were collected or analyzed. The record reports zero analyses and says efficacy outcomes were not assessed.
Finally, the safety counts and the efficacy information answer different questions. The posted adverse-event figures describe events recorded in the study group, while the primary efficacy result is absent. Neither the presence of safety counts nor the study’s terminated status supplies the missing efficacy analysis or explains why it was not assessed. Statistically, the key contribution of this record is to make clear what the planned design was and where the posted evidence stops.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main trial-specific limitation is that the registry record does not report an efficacy analysis, despite defining objective response rate as the primary outcome. It states that efficacy measures were not assessed following changes in planned analysis. The reason for those changes and the reason for termination are not reported in the registry record.
The study enrolled 11 participants and had no control group. Its single-group, open-label design cannot provide a randomized comparison. In addition, the registry does not report participant characteristics, the number who received treatment, or the analysis population and denominator for the planned primary endpoint. The registry record therefore does not allow readers to assess how representative the enrolled group was or how many participants could have contributed to an efficacy assessment.
The record lists secondary outcomes but does not provide numerical results or analyses for them. It does not report the statistical analysis plan, multiplicity handling, missing-data methods, interim analyses, or a trial-specific sample-size justification. These details should not be inferred from the outcome descriptions or from planning illustrations.
Safety information is also limited to the posted figures and event terms. The registry record does not report attribution of adverse events or deaths to treatment, causes of death, or a comparison group. These constraints mean that the record can describe the study and its listed safety counts, but cannot resolve its efficacy question or support causal conclusions from the safety figures.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bintrafusp Alfa in High Mobility Group AT-Hook 2 (HMGA2) Expressing Triple Negative Breast Cancer — NCT04489940.
- Registry record last updated 2023-04-10; status last verified 2023-03.
- Results first posted 2023-04-10.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT04489940 is a phase II, multicenter, open-label, single-group study of bintrafusp alfa monotherapy in participants with HMGA2-expressing triple negative breast cancer. The registry lists 11 participants enrolled, a start date of 2020-10-12, a primary completion date of 2022-01-27, and a status of terminated.
The planned primary outcome was objective response rate according to RECIST version 1.1, assessed by an independent review committee, from first study intervention up to 321 days. The registry states that efficacy outcome measures were not assessed following changes in planned analysis. No primary efficacy estimate or secondary outcome analyses are reported. The record lists seven participants with serious adverse events, nine with other adverse events, and six deaths; it does not establish causal attribution. The reason for termination and the reason for the analysis changes are not reported in the registry record.