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 A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma (NCT04501094), a na phase 2 study. The primary outcome is Proportion of Participants With an Objective Response Rate (ORR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04501094 |
| Phase | Phase 2 |
| Condition | Urothelial Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Adults with urothelial cancer that had spread to other parts of the body and who had previously received chemotherapy or immunotherapy were eligible. The study description separates participants into checkpoint inhibitor-naive and checkpoint inhibitor-refractory groups, with the refractory groups further described by platinum-treatment history or stable or progressive disease.
Intervention
Participants received bintrafusp alfa, also called M7824, as an intravenous infusion once every 2 weeks in 28-day treatment cycles. Treatment was described as continuing until disease worsened, side effects became unacceptable, or participants chose to stop.
Comparator
There was no concurrent control arm. The registry identifies a single-group study, with no allocation to different treatments and no masking. The two participant cohorts are not described as a randomized or like-for-like comparison.
Primary question
The primary question was what proportion of evaluable participants had an objective response, defined as a complete or partial response at the end of treatment. The registry does not report the observed response proportion or its confidence interval, so the clinical question cannot be answered from the posted results.
3. Trial Design
This was a Phase II, single-group study of bintrafusp alfa in participants with urothelial cancer. The registry lists allocation as not applicable and masking as none, so the study was open label. The record describes checkpoint inhibitor-naive and checkpoint inhibitor-refractory participants, including cohorts with different prior-treatment or disease-status characteristics. These cohorts do not constitute a randomized comparison or a concurrent untreated control.
The registry records enrollment of 2 and lists the study as terminated. Its recorded start date is 2020-10-26, and its primary completion date is 2021-01-19. The reason for termination is not reported in the registry record. The record does not provide enough information to determine why enrollment was limited or why the study ended.
Participants were to receive bintrafusp alfa by intravenous infusion once every 2 weeks, within 28-day cycles. The summary describes repeated assessments during treatment and a follow-up visit 30 days after treatment ended. Treatment could continue until disease progression, unacceptable side effects, or a participant's decision to stop. This description is not a substitute for a complete protocol or statistical analysis plan; those details are not reported in the registry record.
The primary endpoint concerned objective response, assessed using RECIST v1.1. Secondary outcomes listed in the registry include toxicity grade >1, progression-free survival, and survival. The registry lists 5 outcome measures, but it does not post numerical primary efficacy results or statistical analyses. The limited enrollment and absent results constrain what can be learned about response, precision, and comparisons between the cohorts.
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.
Overall Study
| Stage | Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease |
|---|---|---|
| STARTED | 1 | 1 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease |
|---|---|---|
| Death (unrelated to research) | 1 | 0 |
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.
| Characteristic | Unit | Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease | Total |
|---|---|---|---|---|
| Participants analysed | 1 | 1 | 2 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 | 0 | 1 |
| Age, Categorical: >=65 years | Participants | 0 | 1 | 1 |
| Age, Continuous | years | 61.3 (SD 0) | 71.5 (SD 0) | 66.4 (SD 7.21) |
| Sex: Female, Male: Female | Participants | 1 | 1 | 2 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 1 | 1 | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Proportion of Participants With an Objective Response Rate (ORR), measured over From time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, approximately 3 months..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Proportion of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the proportion of evaluable participants with an objective response to bintrafusp alfa at the end of treatment. An objective response is defined as either a partial response or a complete response, assessed using RECIST v1.1. A partial response requires at least a 30% decrease in the sum of the diameters of target lesions relative to the baseline sum. A complete response means disappearance of all target lesions.
A response proportion is a binary-outcome summary: each evaluable participant is classified as having or not having the specified response, and the endpoint describes the fraction classified as responders. In general, response endpoints can provide a concise measure of tumor change during a defined assessment period. They do not by themselves describe how long a response lasts, whether disease remains controlled after treatment, or how the treatment compares with another option.
The registry specifies a 95% confidence interval as the dispersion measure. A confidence interval communicates the statistical precision of an estimated response proportion: a wider interval indicates greater uncertainty about the underlying response frequency, while a narrower interval indicates greater precision. The registry record does not report the observed proportion, its confidence interval, or the number of evaluable participants. It therefore does not allow the endpoint's magnitude or precision to be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a Phase II study of bintrafusp alfa in urothelial cancer, but the posted information does not include a numerical result for the primary objective response endpoint. No response proportion, confidence interval, or number of evaluable participants is reported. Consequently, the primary efficacy result cannot be interpreted from the registry record, and no conclusion about the observed frequency or precision of response is warranted.
Enrollment is recorded as 2, and the study status is terminated. This is important context for reading any outcome information: the record describes a very limited study population, and it does not provide a reported primary analysis. The enrollment figure alone does not establish how many participants were evaluable for the endpoint, how many received treatment, or how missing outcomes were handled. Those details are not reported in the registry record.
The study is single group, open label, and has no concurrent control. Any reported outcome would therefore describe what occurred among participants receiving the study treatment, rather than estimate a treatment effect relative to a control group. The separate cohorts also have differing clinical descriptions, so their outcomes should not be treated as a randomized comparison. The registry record does not report an adjusted or unadjusted comparison between them.
The listed secondary outcomes include toxicity grade >1, progression-free survival, and survival. The record does not provide numerical results or analyses for these outcomes. The adverse-event listing names serious-event terms and includes cohort-level figures, but those entries do not fill the gap in the primary efficacy result. They should be read as registry safety reporting, not as evidence of a comparative treatment effect.
The registry status is terminated, but the reason is not reported. It would be inappropriate to infer that termination resulted from efficacy, safety, recruitment, or any other specific cause. Likewise, the record does not establish whether an interim analysis took place, whether the study ended according to a prespecified stopping rule, or whether a planned sample size was reached. These matters are not reported in the registry record.
Overall, the posted data support a description of the intended endpoint, treatment schedule, study structure, enrollment, status, and recorded adverse-event terms. They do not support a quantitative estimate of objective response or a claim that the treatment did or did not have an effect. The central statistical issue is not a subtle interpretation of an estimate; it is the absence of a reported primary result and its uncertainty.
9. Statistical Methods Explained
Statistical interpretation begins with identifying the outcome, the population included in its analysis, and the way the estimate was calculated. For this study, the primary outcome is a proportion: evaluable participants are classified according to whether they had a complete or partial response under RECIST v1.1. The registry specifies a 95% confidence interval as the measure of uncertainty. However, it does not report the response count, denominator, estimate, or interval. Without these elements, readers cannot assess either the observed response frequency or its precision.
What does a confidence interval communicate?
In general, a confidence interval describes uncertainty around an estimate under the assumptions of the statistical method used. For a response proportion, the estimate depends on both the number of participants classified as responders and the number included in the endpoint analysis. With limited information about the analyzed population, readers cannot determine how the interval was obtained or whether it reflects the intended analysis population. No confidence interval is posted for this endpoint, so the statistical uncertainty is not quantifiable from the registry record.
Why does the analysis population matter?
The endpoint is defined for evaluable participants, but the registry does not state how evaluability was determined or report the number evaluated. A study's enrolled population, treated population, and endpoint-evaluable population can differ. In general, exclusions from an endpoint analysis can affect both the estimated proportion and its interpretation, particularly when the reasons for exclusion are related to treatment exposure or outcome assessment. The registry record does not describe such exclusions, the handling of participants without an assessment, or a missing-data strategy.
What can a single-group design estimate?
A single-group study can describe outcomes observed among participants receiving the intervention. It does not, by itself, separate a treatment effect from other explanations for those outcomes, such as the course of disease or differences in participant characteristics. A concurrent control group can support a direct comparison when the design and analysis are appropriate; this study does not have one. Because allocation is listed as not applicable, there is no random assignment to treatment groups. The cohorts described in the registry should not be interpreted as randomized arms.
Open-label status means that masking was absent. In general, knowledge of treatment can influence assessments or reporting, although objective response criteria are intended to apply defined rules to tumor measurements. The registry does not report whether response assessments were independently reviewed, whether assessors were blinded, or what procedures were used to resolve assessment differences. Those design details are not reported in the registry record.
How should the safety listings be interpreted?
Adverse-event summaries describe events recorded in the specified safety population and observation period. The registry lists cohort counts for serious events, other events, and deaths, alongside serious-event terms. These entries are descriptive. They do not establish that the study treatment caused an event, and they do not provide a comparative risk estimate. Interpretation also depends on definitions, follow-up, coding, and the number of participants observed; the registry record does not give all of those details. The percentage attached to a listed serious-event term should not be treated as a treatment-effect estimate.
What do the planning calculations mean?
The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and distinguishes between participants per arm for other outcomes and total events for time-to-event outcomes. These are planning assumptions, not evidence about what was observed in this study. The actual study is single group, and the record does not report a two-arm design or its own sample-size justification. Since a primary observed effect is not posted, those assumptions cannot supply a clinical efficacy result or validate the study's enrollment.
In general, over-dispersion occurs when outcome variability exceeds what a statistical model assumes. Accounting for it can prevent uncertainty from being understated when the model otherwise fits the data poorly. The registry record does not identify a model for the primary endpoint or report whether over-dispersion was assessed. No model-specific conclusions can therefore be drawn.
The registry lists no analyses. It does not report the estimator, confidence-interval method, covariate adjustment, prespecified analysis hierarchy, or sensitivity analyses. Such details matter because different analytic choices can lead to different estimates or uncertainty intervals, particularly when the population is small or outcome information is incomplete. These methods are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary response endpoint and secondary outcomes that include toxicity grade >1, progression-free survival, and survival. It does not report a multiplicity procedure or an ordering of hypotheses. In general, when several outcomes or comparisons are tested, the chance of a false-positive finding can increase unless the analysis plan addresses multiplicity. No confirmatory interpretation of multiple statistical tests can be made from the registry record because no analyses are posted and the approach to multiplicity is not reported.
The record does not describe missing-data rules, how participants without an endpoint assessment were handled, or whether any sensitivity analysis was planned. It also does not give the endpoint-evaluable population. These omissions matter for a proportion endpoint because the denominator and classification of participants without an assessment affect the interpretation of the estimate. No assumptions about missing responses should be made.
The registry identifies the primary endpoint as applying to evaluable participants, but it does not define the analysis population in further detail. It does not report whether an intention-to-treat, treated, or other population was used. The registry lists 0 analyses. Interim analyses, stopping boundaries, and a prespecified statistical analysis plan are not reported in the registry record. The status of terminated does not, on its own, establish what analytic decisions were made or why.
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 |
|---|---|---|---|
| Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | 1 | 1 | 100.0% |
| Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | 1 of 1 |
| Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | 1 of 1 |
| Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease |
|---|---|---|---|
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Death from progressive | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 1 | 0 of 1 |
| Pain | General disorders | 1 of 1 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1B - Checkpoint Inhibitor Naïve Participants Who Are Refractory Post-platinum Therapy | Cohort 2B - Checkpoint Inhibitor Refractory Participants With Stable Disease or Progressive Disease |
|---|---|---|---|
| Lymphocyte count decreased | Investigations | 1 of 1 | 1 of 1 |
| Anemia | Blood and lymphatic system disorders | 1 of 1 | 0 of 1 |
| Bacteremia | Infections and infestations | 1 of 1 | 0 of 1 |
| Bruising | Injury, poisoning and procedural complications | 0 of 1 | 1 of 1 |
| Diarrhea | Gastrointestinal disorders | 1 of 1 | 0 of 1 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 0 of 1 | 1 of 1 |
| Fatigue | General disorders | 0 of 1 | 1 of 1 |
| Headache | Nervous system disorders | 0 of 1 | 1 of 1 |
| Hypertension | Vascular disorders | 1 of 1 | 0 of 1 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 1 of 1 | 0 of 1 |
Serious events with the highest arm-level rate: neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, death from progressive (100.0%), pain (100.0%).
The safety listing separates two cohorts: checkpoint inhibitor-naive participants refractory after platinum therapy, and checkpoint inhibitor-refractory participants with stable or progressive disease. Each cohort is listed with one participant at risk for serious adverse events and one at risk for other adverse events. The record lists one serious adverse event and one other adverse event in the first cohort; in the second, it lists no serious adverse events and one other adverse event. Deaths are listed as one and zero, respectively.
The serious-event terms include death from progressive disease under a neoplasms category and pain; each is displayed as 100.0%. These percentages are descriptive registry entries, not estimates comparing treatments. The record does not establish that a listed event was caused by bintrafusp alfa. Nor does it provide the duration of individual safety observation or further detail about event attribution and coding. With the small listed safety populations and no control group, the entries cannot quantify comparative safety or establish a causal relationship.
12. What the Result Does, and Does Not, Mean
The record establishes that a Phase II study of bintrafusp alfa was registered for urothelial cancer, that the design was single group and open label, and that the study was terminated. It describes an intended primary endpoint based on complete or partial response by RECIST v1.1, as well as a treatment schedule and selected safety outcomes. The posted safety information includes cohort-level event figures and serious-event terms.
It does not establish the observed objective response proportion, its confidence interval, the number of evaluable participants, or the results of the listed secondary outcomes. No statistical analyses are posted. The record also does not explain the reason for termination, document a sample-size justification, or state how missing outcomes and multiple endpoints were handled. These gaps prevent a quantitative assessment of efficacy and limit interpretation of safety.
A response endpoint is not the same as a comparison with another treatment, and an event count is not by itself evidence of causation. Because there is no concurrent control group, the study design cannot directly estimate a comparative treatment effect. The registry information does not support saying that bintrafusp alfa works or does not work. It supports only a careful account of the study's stated question, structure, and posted data, while making clear that the primary result is not reported in the registry record.
13. Why This Trial Matters Statistically
This record illustrates why registry status and numerical results should be read separately. The study is marked terminated, but that status does not say why it ended, what analyses were conducted, or whether the primary endpoint was met. The registry records enrollment of 2, yet provides no numerical objective response result, analysis population, or confidence interval. Statistical interpretation depends on those outcome details, not on the study label alone.
The design also clarifies the distinction between describing outcomes and estimating a treatment effect. A single-group study can report what happened among those treated, but without a concurrent comparator it cannot make a direct randomized comparison. Separate clinical cohorts do not remedy that limitation when they are not assigned as comparable groups.
For readers evaluating evidence, the key contribution of this record is therefore methodological context rather than an estimate of treatment benefit. It specifies a response definition, a confidence-interval measure, treatment delivery, and safety categories, while leaving the main efficacy result and important analysis details unreported. Recognizing this boundary helps prevent registry descriptions, planning illustrations, or safety listings from being mistaken for a complete statistical assessment.
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 principal limitation is that the registry record does not report a numerical primary endpoint result. It also omits the response count, endpoint denominator, confidence interval, and number of evaluable participants. As a result, neither the magnitude nor precision of the primary outcome can be assessed.
Enrollment is recorded as 2, and the study is terminated. The record does not explain the termination or provide enough detail to assess whether follow-up and outcome collection were complete. The duration of safety observation, missing-data handling, analysis populations, and methods for response assessment beyond the stated RECIST v1.1 criteria are not reported in the registry record.
The study is open label and has no concurrent control group. Its cohorts have different clinical descriptions and do not provide a randomized comparison. The record does not report adjustment for baseline differences, an analysis plan, multiplicity handling, interim analyses, or the reason for choosing the enrollment target. The planning assumptions described in the registry are not evidence of the actual study design or a justification for its enrollment. Together, these limitations mean that the record supports a description of the registered study but not a reliable quantitative assessment of efficacy or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Phase II Study of Bintrafusp Alfa (M7824) in Checkpoint Inhibitor Naive and Refractory Subjects With Urothelial Carcinoma — NCT04501094.
- Registry record last updated 2022-03-22; status last verified 2022-02.
- Results first posted 2022-03-22.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This Phase II study evaluated bintrafusp alfa in checkpoint inhibitor-naive and refractory participants with urothelial cancer. The design was open label and single group, with no concurrent control. The registry records enrollment of 2, a start date of 2020-10-26, a primary completion date of 2021-01-19, and terminated status.
The primary endpoint was the proportion of evaluable participants with a complete or partial response under RECIST v1.1, with a 95% confidence interval specified. The registry does not report the primary result, its interval, or any statistical analyses. It lists selected secondary outcomes and descriptive safety information, but does not report the reason for termination or key analysis details. The record therefore describes the study and its intended outcomes without providing a quantitative primary efficacy finding.