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 Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung Cancer (NCT04560686), a na phase 2 study. The primary outcome is Major Pathologic Response (MPR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04560686 |
| Phase | Phase 2 |
| Condition | Resectable Lung Non-Small Cell Carcinoma, Stage I Lung Cancer AJCC v8, Stage IA1 Lung Cancer AJCC v8 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with untreated, resectable non-small cell lung cancer. The registry lists several stages, from Stage I through Stage IIIB, including substages. Enrollment is recorded as 2. The primary endpoint description says data were not collected, so the record does not establish an analyzed population for that endpoint.
Intervention
Participants in the single treatment group were to receive bintrafusp alfa by intravenous administration on days 1, 15, and 29, unless unacceptable toxicity occurred. Surgery was planned within 4-6 weeks after the last dose, at the treating surgeon’s discretion. The registry also lists therapeutic conventional surgery as an intervention.
Comparator
There was no separate comparator group. The design is listed as single-group, with allocation recorded as NA and masking as none. Consequently, the study was not set up to estimate a randomized between-group treatment contrast. Outcomes in the treatment group cannot, by themselves, separate treatment effects from other explanations.
Primary question
The primary endpoint was major pathologic response at surgery: the proportion of resected specimens with 10% or less viable tumor cells. The study description planned to estimate that rate with a 95% credible interval using a beta prior. However, the registry states that data were not collected for the primary endpoint. It therefore does not report an observed response rate or an interval estimate.
In practical terms, the research question was whether this preoperative treatment strategy could be evaluated through tumor findings in tissue removed at surgery. The endpoint focuses on the tumor remaining in the resected specimen, rather than on symptoms or survival. That makes it a measure of pathologic response at a defined treatment stage, not a direct comparison of long-term outcomes.
The registry describes the treatment as investigational and the study as phase II. Its brief summary gives a rationale for administering immunotherapy before surgery, but a rationale is not evidence of benefit. With no collected primary endpoint data recorded and no comparator group, this record cannot establish whether bintrafusp alfa changed pathologic response relative to another treatment strategy.
3. Trial Design
This was a phase II, single-group study sponsored by M.D. Anderson Cancer Center. The registry lists the study start as 2020-08-05, primary completion as 2021-07-01, and status as terminated. Enrollment is recorded as 2. The record does not explain why the study was terminated or provide a detailed account of the circumstances surrounding its conduct.
The study population was described as patients with untreated, surgically resectable non-small cell lung cancer. The registry’s condition list spans Stage I through Stage IIIB, with several Stage I subdivisions. These entries describe the intended disease scope; they do not show which disease stages were represented among participants or define the characteristics of an analyzed population.
The treatment group was to receive bintrafusp alfa intravenously on days 1, 15, and 29, if there was no unacceptable toxicity. Surgery was planned within 4-6 weeks after the final dose, at the surgeon’s discretion. The record also says that chemotherapy or radiation might be given after surgery within 8 weeks, but the postoperative arm description ends mid-word after “radia”. The full postoperative description is therefore not reported in the registry record.
Allocation is listed as NA, masking as none, and the model as single group. These entries indicate that the study was not a masked randomized comparison. The registry lists surgery as well as bintrafusp alfa among the interventions, reflecting the sequence of preoperative treatment followed by resection. It does not give a separate control arm receiving surgery alone or another preoperative regimen.
The primary endpoint was major pathologic response at surgery. Secondary outcomes include adverse events, peri-operative morbidity and mortality, induction response rates, recurrence-free survival, and overall survival. The record lists repeated entries for recurrence-free and overall survival, but does not provide a detailed analysis plan for those outcomes. The study’s termination and lack of collected primary endpoint data limit what can be learned from its planned design.
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: Two participants were consented; one screen failure. The trial was terminated earlier than planned due to an administrative decision taken by the PI/co-PI in collaboration with the study sponsor based on emerging data made available with the investigational agent being tested in other diseases in the perioperative setting.
Overall Study
| Stage | Arm A: M7824 , Surgery, SOC Post-Op |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Data were not collected.
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 | Arm A: M7824 , Surgery, SOC Post-Op |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| 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 | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Major Pathologic Response (MPR), measured over At time of surgery.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
Major pathologic response (MPR) was the primary endpoint, assessed at the time of surgery. The registry defines it as 10% or less viable tumor cells in the resected specimen, using methods attributed in the record to Pataer et al. The endpoint is a binary classification at the specimen level: a resected tumor either meets the stated viable-cell threshold or does not. The intended rate would describe the share of evaluated specimens meeting that definition.
Pathologic response is used in neoadjuvant research because it assesses tumor tissue after preoperative treatment and at the time of planned surgery. It can provide a measure of treatment-associated change in the tumor that is distinct from later outcomes such as recurrence or survival. As a general statistical point, an endpoint must be defined consistently so that classifications can be compared across participants and studies; the registry gives a threshold for this endpoint but does not report collected MPR data.
The study description planned to estimate the MPR rate with a 95% credible interval, using a beta prior described as (0.5, 0.5) with one patient worth of information. This is a stated analysis plan, not a reported estimate. The registry explicitly says that data were not collected for the primary endpoint. It therefore provides neither an observed MPR rate nor an interval describing uncertainty around such a rate.
MPR should not be treated as interchangeable with recurrence-free survival, overall survival, or peri-operative outcomes. Those outcomes address different questions and have different time structures. The record lists them as secondary outcomes, but it does not provide their analysis results in the information available for this study.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive fact is that the registry record says primary endpoint data were not collected. Although the endpoint and a planned estimation approach are described, no observed major pathologic response rate is reported. There is consequently no MPR estimate to interpret, and no confidence or credible interval showing its precision. The planned definition and method should not be mistaken for completed results.
Enrollment is recorded as 2, but enrollment alone does not supply an outcome denominator. The registry does not say how many participants underwent surgery, had an evaluable resection specimen, or contributed to any endpoint analysis. It also does not report participant-level MPR classifications. No assumptions about those details can substitute for endpoint data.
The single-group structure matters. Even if an outcome estimate had been reported, there would be no randomized control group in this design against which to estimate a treatment contrast. A single-group result can describe what was observed among participants, but cannot by itself establish what would have happened to comparable participants under another strategy. Differences in patient characteristics, clinical decisions, natural disease course, and other care can complicate causal interpretation.
The registry lists the study as terminated. The reason for termination is not reported in the registry record. Termination is relevant context for understanding why the record may not contain the anticipated endpoint results, but it does not establish the cause of missing data or imply a particular safety or efficacy finding.
The safety record should also be read narrowly. It reports one serious adverse event affected and at risk in the listed group, and identifies pneumothorax at 100.0% among the top serious terms. The group’s recorded count is small, and the record does not provide a comparative safety rate. The percentage therefore describes the registry’s listed serious-event entry and should not be interpreted as a stable estimate of risk in a broader population.
Secondary outcomes are named, including adverse events, peri-operative morbidity and mortality, induction response, recurrence-free survival, and overall survival. Naming an outcome does not mean an estimate is available. The registry record does not report analyses for these endpoints in the registry record describing this study. In particular, no survival curve, hazard estimate, or comparative effect can be inferred from outcome titles alone.
Overall, the record documents a planned preoperative treatment study and a small recorded enrollment, but it does not provide the primary outcome data needed to quantify pathologic response. It also lacks a randomized comparator. The evidence in this record is therefore descriptive of the study plan and its status, rather than evidence establishing an effect on MPR, survival, or safety relative to another approach.
9. Statistical Methods Explained
The registry describes an intended Bayesian estimation of the major pathologic response rate. The planned prior is a beta distribution with parameters (0.5, 0.5), described as providing one patient worth of information, and the target summary is a 95% credible interval. These details describe the stated method. Because the record says primary endpoint data were not collected, they do not yield a posterior estimate for this study.
What does a credible interval mean?
As a general statistical explanation, a credible interval is an interval calculated from a posterior distribution. Under the Bayesian model, it expresses uncertainty about an unknown quantity, conditional on the observed data and the prior assumptions. A 95% credible interval is intended to contain 95% of the posterior probability for the quantity under that model. It is not the same construction as a frequentist confidence interval, which is interpreted through the long-run behavior of a procedure across repeated samples.
The interpretation depends on the likelihood, the prior, and the data. For a response-rate endpoint, the data would need to identify how many evaluated specimens met the MPR definition and how many were evaluated. Neither an observed response count nor an evaluable denominator is reported for the primary endpoint. Without those data, there is no study-specific posterior distribution to summarize, even though the registry describes the planned prior and interval.
Why use a beta prior for a rate?
As a general explanation, a beta distribution is commonly used to represent uncertainty about a probability or rate constrained between zero and one. In a simple binomial model, the observed outcomes update the prior distribution to produce a posterior distribution for the response probability. The beta prior can place different degrees of probability across possible rates, so the choice of prior can affect inference, particularly when the data are sparse. The record’s stated prior is part of its planned analysis specification; it is not evidence that an analysis was completed.
The description that the prior represents one patient worth of information is a way to convey its intended contribution relative to observed data. It does not mean that a participant’s endpoint result was recorded. Nor does it replace the need to know the actual number of evaluable specimens and responses. Since MPR data were not collected according to the record, readers cannot assess the observed-data contribution or determine the resulting interval.
What can an interval say about precision?
In general, an interval communicates uncertainty as well as a point estimate. A narrower interval indicates greater concentration of the estimate under the stated model; a wider interval indicates more uncertainty. With a limited amount of outcome information, estimates are generally less precise than they would be with more informative data, though the actual precision depends on the design, outcome pattern, and model. No study-specific interval width can be discussed for MPR because none is reported.
An interval does not remove design limitations. Even a precisely estimated single-group response rate would describe that group under the study conditions, not a causal difference versus a comparator. Precision and causal validity are separate properties: an estimate may be precise for a descriptive quantity while still not identify the effect of treatment relative to another strategy.
How should the design affect interpretation?
As a general statistical point, random allocation helps balance measured and unmeasured prognostic factors between treatment groups, on average, and supports estimation of a treatment contrast. This study is listed as single group, with allocation NA and no masking. It therefore has no like-for-like randomized control comparison. A result from the treatment group alone could not isolate treatment effects from other causes of the observed outcome.
Masking is also listed as none. For a tissue-based endpoint, the registry does not report whether pathologic assessments were conducted independently or under blinded review. That detail is not reported in the registry record. General concerns about assessment bias should not be turned into a claim that bias occurred; the record does not establish that.
The study description gives the surgical timing as within 4-6 weeks after the last dose, at the treating surgeon’s discretion. This makes clear that surgery was part of the planned treatment pathway, but does not establish whether surgery occurred for participants or when it occurred. Those details are not reported in the registry record.
How should planning illustrations be read?
Any sample-size figures associated with observed effects are planning illustrations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. The illustrations are not the trial’s own design, and the study itself is listed as single group. They should not be read as a trial power analysis or as evidence that the study had a particular probability of detecting an effect.
In general, sample-size planning asks what information a future design might need under explicit assumptions about an effect, variability, allocation, and error rates. Such calculations do not create evidence about an outcome and do not compensate for absent endpoint observations. The registry does not report the study’s own sample-size justification. No planning figure can be interpreted as observed response, observed power, or a substitute for the missing MPR data.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple secondary outcomes: adverse events, peri-operative morbidity and mortality, induction response rates, recurrence-free survival, and overall survival. It also includes repeated entries for recurrence-free and overall survival. However, the registry record does not report a multiplicity strategy, such as a hierarchy of hypotheses, an adjustment procedure, or a distinction between confirmatory and exploratory tests. The number and organization of listed outcomes alone do not reveal how statistical error across analyses was intended to be controlled.
Multiplicity is a general concern when several hypotheses are tested: the chance of at least one apparently notable result can rise as the number of tests increases, depending on their relationships and the analysis strategy. This concept does not establish that a false-positive finding occurred in this study. The record does not report outcome analyses for which such a finding could be assessed.
Missing data are a more immediate interpretive issue. For the primary endpoint, the registry states that data were not collected. It does not report reasons, timing, participant flow, surgery completion, specimen evaluability, or any method for handling missing endpoint observations. It is therefore not possible to distinguish a planned endpoint that was never measured from other possible forms of unavailable data based on this record alone.
Analysis populations are not described in sufficient detail. The registry record does not report whether analyses were intended for all enrolled participants, those receiving treatment, those undergoing surgery, or those with evaluable specimens. It also does not report endpoint-specific denominators. These omissions prevent assessment of how participants would have been included in outcome summaries.
The planned Bayesian method for MPR does not resolve these issues. A model can describe uncertainty given data and assumptions, but it cannot recover uncollected outcomes without additional assumptions that are not reported. The registry does not describe a missing-data model or a sensitivity analysis for the primary endpoint.
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 |
|---|---|---|---|
| Arm A: M7824 , Surgery, SOC Post-Op | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A: M7824 , Surgery, SOC Post-Op | 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 |
|---|---|
| Arm A: M7824 , Surgery, SOC Post-Op | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A: M7824 , Surgery, SOC Post-Op |
|---|---|---|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: M7824 , Surgery, SOC Post-Op |
|---|---|---|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 1 of 1 |
| Bone pain | Musculoskeletal and connective tissue disorders | 1 of 1 |
| Fall | Injury, poisoning and procedural complications | 1 of 1 |
Serious events with the highest arm-level rate: pneumothorax (100.0%).
The serious adverse event entry lists one participant at risk and one affected in the reported group, with zero deaths recorded. Pneumothorax is listed as the top serious term at 100.0%. These are the figures reported for that group; they are not a comparative estimate against another treatment, because the study is single group and no comparator arm is listed.
The percentage needs context. It reflects the serious-event term and denominator recorded in the registry, which is one in the group entry. With such a limited recorded denominator, the percentage is highly sensitive to the experience of the individual represented. It should not be generalized as a population risk estimate, nor should it be read as a stable estimate of the frequency of pneumothorax among all patients receiving this treatment strategy.
The record does not provide enough detail to determine the timing, severity grade, causal attribution, duration, or clinical course of the pneumothorax. It also does not report a complete narrative of the event. These details are not reported in the registry record. A serious adverse event listing is not, by itself, proof that the study treatment caused the event.
Safety figures should be distinguished from the study’s primary MPR endpoint. The record states that MPR data were not collected; the serious adverse event entry does not fill that gap or answer the primary efficacy question. The study’s terminated status also does not establish why it ended or whether the event contributed to termination.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase II, single-group study of bintrafusp alfa before surgery was planned for untreated, resectable non-small cell lung cancer. It records enrollment as 2, identifies major pathologic response as the primary endpoint, and lists the study status as terminated. It also states that data were not collected for the primary endpoint. These registry entries describe the study and the limits of the available outcome evidence.
The record does not establish an MPR rate. There is no reported response count, evaluable specimen count, point estimate, or credible interval for that endpoint. The planned Bayesian method is not a substitute for observed tissue outcomes. Nor does the registry provide a primary endpoint finding that could be interpreted as favorable, unfavorable, or inconclusive.
The design cannot estimate a randomized treatment contrast because there is no control group. Even if a response rate were available, the single-group design would not show what would have occurred under surgery alone or another preoperative regimen. The record therefore cannot establish that bintrafusp alfa caused a response, altered recurrence, affected survival, or changed peri-operative outcomes.
The secondary outcomes listed in the record likewise do not constitute results. Outcome names indicate what the study intended to assess, not what happened or what was analyzed. The serious-event entry is a limited descriptive safety record and does not provide a comparative rate or establish causation.
The study should not be interpreted as demonstrating that the treatment works or does not work. The appropriate conclusion is narrower: the registry documents a planned single-group study with enrollment recorded as 2, but it does not report collected primary endpoint data. The reason for termination, analysis populations, participant flow, and detailed results for the listed secondary outcomes are not reported in the registry record. Any conclusion beyond those statements would require evidence not contained in this record.
13. Why This Trial Matters Statistically
The study illustrates an important distinction between a registered statistical plan and an analyzed result. The record specifies a primary endpoint, a threshold for classifying major pathologic response, and a Bayesian estimation approach. Yet it also states that primary endpoint data were not collected. A well-defined endpoint and model describe how evidence might have been summarized; they do not provide evidence when the outcome itself is unavailable.
It also shows why the design determines the question that can be answered. A single-group study can potentially describe outcomes within its treatment pathway, but it cannot provide the same direct treatment contrast as a randomized comparison. Without a comparator, statistical precision for a within-group rate would not resolve the central causal question of what would have happened under another strategy.
Registry status and enrollment are important context, but they are not substitutes for participant flow or outcome denominators. Enrollment is recorded as 2, while the record does not specify how many participants had surgery or evaluable tissue. For endpoint interpretation, that distinction matters because the relevant denominator depends on the endpoint and analysis population.
The safety entry further demonstrates why denominators must accompany percentages. A reported 100.0% for pneumothorax is tied to a very limited group entry, not a broad population estimate. Statistical interpretation requires attention to both the numerator and the number of people whose outcomes could have been observed, as well as the study design and event definitions.
Finally, the record underscores the value of separating planned methods from completed analyses. The prior, credible interval, secondary outcomes, and sample-size assumptions provide methodological context, but they cannot be treated as observed results. Clear reporting of endpoint collection, analysis populations, and missingness would be needed to support stronger conclusions.
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 most consequential limitation is the registry’s statement that primary endpoint data were not collected. No MPR result or interval estimate is available, despite the endpoint’s definition and planned Bayesian method. As a result, the primary research question cannot be answered from this record.
Enrollment is recorded as 2, but participant flow is not reported. The record does not say whether participants received all planned doses, underwent surgery, or had specimens suitable for MPR assessment. It also does not provide endpoint-specific denominators or explain why primary endpoint data were not collected.
The single-group design has no randomized comparator. Any within-group outcome, if one were available, could not alone estimate the causal difference between bintrafusp alfa and another treatment strategy. Masking is listed as none, and details of endpoint assessment procedures are not reported in the registry record.
The study is listed as terminated, but the reason for termination is not reported in the registry record. The record does not establish whether termination was related to recruitment, operational circumstances, safety, efficacy, or another reason. The listed dates and status should not be used to infer an explanation.
Several secondary outcomes are named, but detailed results and analysis methods are not reported in the registry record. Multiplicity handling, analysis populations, and missing-data methods are also not reported. The postoperative arm description is incomplete, ending after “radia”, so the full description of possible postoperative care is unavailable.
The serious adverse event information is sparse and has a very limited recorded denominator. It does not provide event timing, severity grade, causal attribution, or a comparator. These limitations prevent generalization of the listed percentage and prevent a full assessment of the safety experience.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bintrafusp Alfa Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung Cancer — NCT04560686.
- Registry record last updated 2022-07-28; status last verified 2022-07.
- Results first posted 2022-07-28.
- 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
This phase II study evaluated a planned strategy of bintrafusp alfa before surgery for untreated, resectable non-small cell lung cancer. The design is listed as single group, with no masking, and enrollment recorded as 2. The registry lists M.D. Anderson Cancer Center as sponsor, a start date of 2020-08-05, primary completion of 2021-07-01, and status as terminated.
The primary endpoint was major pathologic response at surgery, defined as 10% or less viable tumor cells in the resected specimen. The planned analysis used a beta prior and a 95% credible interval. The registry states that data were not collected for this endpoint, so no MPR estimate is reported. The reason for termination, participant flow, analysis populations, missing-data methods, and detailed secondary outcome results are not reported in the registry record.
The serious adverse event record lists pneumothorax at 100.0% in a group entry with one affected and one at risk, and zero deaths. Given the single-group design and very limited denominator, this is a descriptive entry, not a comparative safety estimate.