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 MK-3475 Immunotherapy in Endometrial Carcinoma (NCT02630823), a na phase 1 study. The primary outcome is Safety as Measured by Any Grade Treatment Related Adverse Events Experienced by ≥ 2 Patients.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02630823 |
| Phase | Phase 1 |
| Condition | Endometrial Cancer, Endometrial Carcinoma, Neoplasms, Endometrial |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 10 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Washington University School of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
Participants with surgically resectable endometrial carcinoma were the study population. The registry record lists an enrollment of 10. Further eligibility details, including participant characteristics and selection criteria, are not reported in the registry record.
Intervention
The study examined MK-3475, also called pembrolizumab in the study summary, before surgery. Participants were to have an endometrial biopsy followed by 2 doses of MK-3475 3 weeks apart. Surgical resection and subsequent standard-of-care adjuvant therapy were part of the described treatment sequence.
Comparator
There was no concurrent control group. The record describes a single-group study and lists allocation as not applicable. Standard-of-care surgery and adjuvant treatments were included in the sequence, but they were not a separate comparison arm.
Primary question
The primary safety question concerned any-grade treatment-related adverse events experienced by at least 2 participants. The registry record does not report a numerical primary endpoint result, so it is not possible to determine from the posted results how many participants met that endpoint criterion.
The study also sought to examine the tumor environment before and after MK-3475 exposure. Its summary describes collecting a research-related endometrial biopsy before treatment and surgical tissue after treatment. This makes the investigation different from a comparative trial asking whether one treatment produces better clinical outcomes than another: the design centered on a treatment sequence in a small group, with safety as the stated primary endpoint and biological evaluation as a stated rationale.
Progression-free survival is listed as a secondary outcome. A result for that outcome is not reported in the registry record. Because there was no control group, the design does not provide a randomized treatment contrast. The clinical question that can be addressed by the posted information is therefore limited to what was planned and what safety counts are recorded, rather than a comparison of treatment effects.
3. Trial Design
This was a completed phase 1, single-group study sponsored by Washington University School of Medicine. The registry record lists 10 participants as enrolled. It does not describe random assignment or a concurrent control group, and masking was listed as none. These design features matter when interpreting outcomes: results from the group can describe events during the study, but there is no parallel group in the registry record against which to compare them.
The treatment sequence began with an endometrial biopsy, followed by 2 doses of MK-3475 3 weeks apart. The description states that standard-of-care surgical resection would take place 3-4 weeks after the second dose, followed by standard-of-care adjuvant therapy. The listed standard-of-care interventions include surgery, paclitaxel, carboplatin and radiation. Tissue and blood collection are also listed. The record's description of the arm ends mid-sentence, so additional details about collection procedures are not reported in the registry record.
The study began on 2016-02-05, reached primary completion on 2019-01-01, and is marked completed. The primary endpoint timeframe was through 90 days following the last dose of MK-3475, described as approximately 56 weeks. This timeframe defines the period specified for the primary safety outcome; it does not establish that every participant received the same duration of follow-up.
As a single-group study, the design can describe safety events and biological observations in participants treated according to the study sequence. It cannot by itself separate effects associated with MK-3475 from events associated with surgery, subsequent standard-of-care treatment, the underlying disease, or other factors. The registry record does not report a protocol rationale for the enrollment target or further details of the statistical 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.
Overall Study
| Stage | Arm 1: MK-3475 |
|---|---|
| STARTED | 10 |
| COMPLETED | 8 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Arm 1: MK-3475 |
|---|---|
| Withdrawal by Subject | 1 |
| Did not undergo cytoreductive surgery due to pre-operative disease progression | 1 |
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 1: MK-3475 |
|---|---|---|
| Participants analysed | 10 | |
| Age, Continuous | years | 60 (46 to 71) |
| Sex: Female, Male: Female | Participants | 10 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 9 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 |
| Race (NIH/OMB): White | Participants | 7 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Safety as Measured by Any Grade Treatment Related Adverse Events Experienced by ≥ 2 Patients, measured over Through 90 days following last dose of MK-3475 (approximately 56 weeks).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled as safety measured by any-grade treatment-related adverse events experienced by at least 2 participants. It is a participant-count outcome: the relevant quantity is how many participants had an event meeting the endpoint definition, not how many separate event episodes occurred. The adverse-event grading approach is identified as the revised NCI Common Terminology Criteria for Adverse Events, version 4.0. The specified observation period is through 90 days following the last MK-3475 dose, approximately 56 weeks.
A safety endpoint is used in an early-phase study to describe adverse events observed during treatment and follow-up. Grading gives a structured way to classify event severity, while the treatment-related wording indicates that attribution to treatment is part of the endpoint definition. The threshold of at least 2 participants specifies which event frequencies the endpoint title focuses on. It does not mean that events occurring in fewer participants could not be relevant to safety; it defines the stated endpoint criterion.
The registry record does not report a numerical result for this primary endpoint, nor does it report the event terms included in the endpoint count or a participant-level breakdown. The serious adverse event counts are separate safety information and should not be substituted for the primary endpoint: seriousness and grade are distinct concepts, and the primary endpoint explicitly concerns treatment-related events of any grade.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study enrolled 10 participants and had a single-group design. The posted safety information reports that 1 of 10 participants was affected by a serious adverse event, while 10 of 10 were affected by other adverse events. Five deaths are recorded. These counts describe what the registry lists; they do not by themselves establish whether an event was caused by MK-3475 or by another part of the treatment sequence. The registry record does not report the cause of death or a numerical result for the primary endpoint of treatment-related events.
Three serious adverse event terms are listed: congestive heart failure, pulmonary pretension and hypotension, each with a recorded frequency of 10.0%. The record does not give event-specific counts alongside those percentages or explain whether the terms overlap. The percentages should therefore be read as registry-reported figures, not as evidence that the events were attributable to treatment. The label “serious” describes a category of adverse event and is not interchangeable with the primary endpoint's “any grade” wording.
Progression-free survival is listed as a secondary outcome, but a numerical result is not reported in the registry record. There is consequently no posted estimate or uncertainty interval for that outcome to interpret. The registry record also reports no statistical analyses. It does not provide an estimate of treatment effect, a confidence interval, or a hypothesis-test result for the primary endpoint.
With no concurrent comparison group, the safety counts are descriptive. They cannot estimate how event rates would have differed under another treatment or without MK-3475. The study's sequence included surgery and standard-of-care adjuvant therapy, so the record does not offer a design-based way to distinguish events associated with each component. In general, a confidence interval expresses the precision of an estimated quantity under a statistical model; no such interval for the primary safety result is reported in the registry record.
The small enrollment also means that counts should be interpreted as observations among the participants in this study, not as a precise characterization of event frequency in a broader population. This is a general limitation of interpreting small descriptive samples. No formal uncertainty estimate is reported, and no conclusion about comparative safety or efficacy follows from the available counts alone.
9. Statistical Methods Explained
What does a single-group design tell us?
In a single-group study, participants receive the study treatment sequence and outcomes are described within that group. Such a design can document events occurring during the observation period and can support exploratory study of biological changes. It does not create a concurrent control group. Without a control group, the contrast needed to estimate how outcomes differ under an alternative treatment is absent. General statistical interpretation therefore treats the safety counts as descriptive rather than as a comparative treatment effect.
This distinction is especially important when a treatment sequence includes multiple components. The registry describes MK-3475 before surgical resection, followed by standard-of-care adjuvant therapy. If an event occurs during follow-up, timing and clinical attribution may help characterize it, but the single-group design alone cannot identify which component caused it. The registry record does not report a component-specific causal analysis.
How should a participant count be read?
The primary endpoint is expressed as a count of participants meeting an adverse-event criterion. Participant counts and event counts answer different questions. A participant may experience more than one event, while a participant-level endpoint generally counts that person once if the endpoint condition is met. The primary endpoint title focuses on treatment-related events of any grade experienced by at least 2 participants. The numerical count meeting that definition is not reported in the registry record, so it cannot be reconstructed from the serious-event summary.
In general, adverse-event summaries depend on their definitions: the event window, severity grading, attribution, and whether results count participants or episodes. The record identifies the CTCAE version and a timeframe for the primary endpoint. It does not report detailed rules for handling repeated events, multiple terms in one participant, or uncertain attribution. These details matter because different counting rules can produce different summaries from the same underlying clinical observations.
What is the role of confidence intervals and tests?
In general, a confidence interval describes the range of values reasonably compatible with an estimate under the assumptions of the statistical method. Its width communicates precision: a wider interval indicates greater uncertainty than a narrower interval. A hypothesis test evaluates a specified null hypothesis under a statistical model. These tools do not replace the need to understand the design, endpoint definition, and data quality.
No confidence interval, hypothesis-test result, or numerical estimate for the primary endpoint is reported in the registry record. There are no posted analyses listed. Therefore, interpretation should not imply that statistical significance was assessed or that a treatment effect was estimated. The reported participant counts and event-term frequencies are descriptive information, not a substitute for an inferential analysis.
What do the planning assumptions mean?
In general, a sample-size calculation is a planning exercise: it estimates how much information a future study may need under specified assumptions about the effect, significance level, allocation, and statistical model. It does not report the outcome observed in the completed study. A planning illustration based on an observed effect is distinct from a protocol's prospective design justification, and its assumptions need to match the design being considered.
The registry record does not report the trial's sample-size justification. A planning illustration is described with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not describe this trial's single-group design. The illustration therefore should not be treated as the study's own design plan or as a direct description of the information collected from its participants. Its numerical planning results are not reported in the registry record. Any sample sizes in such a planning context are hypothetical design quantities, not observed participant counts and not evidence of the study's precision.
General planning calculations are also sensitive to the assumed effect. If the effect used for planning is derived from a small study, it may be imprecise. A planning result should be interpreted as conditional on its assumptions, rather than as a guarantee that a future study will detect an effect. The registry record does not report an original protocol calculation, a target effect, or the rationale for enrolling 10 participants.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variation in count data exceeds what a chosen probability model expects. If a model assumes less variability than is present, its standard errors may be too small and its intervals too narrow. Methods that allow extra variation can yield uncertainty estimates that better reflect heterogeneity, when the data and design support those methods.
The primary endpoint is a participant count, and the registry record does not report a model-based analysis of that endpoint. There is no reported dispersion estimate or analysis method to assess. Over-dispersion is therefore a general statistical consideration, not a reported feature of this study. The available registry information supports a descriptive reading of counts, not a claim that a particular count model was fitted.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists the primary safety endpoint and names progression-free survival as a secondary outcome. It does not report a multiplicity strategy, such as a prespecified method for controlling the chance of false-positive findings when assessing multiple outcomes. No statistical analyses are listed, so there are no posted outcome-specific tests to interpret in light of multiplicity. The existence of more than one outcome does not by itself establish that confirmatory testing occurred.
Missing-data handling is not reported in the registry record. The record does not state how participants with incomplete follow-up, missing assessments, or unavailable outcome information were handled. It also does not report the number of participants with evaluable primary endpoint data, or explain whether missing safety observations were considered absent events. These details affect interpretation because observed counts depend on which participants and follow-up periods contribute information.
Analysis populations are not reported in the registry record. The posted enrollment is 10, but the record does not specify whether every enrolled participant was included in each outcome summary, nor does it describe a safety population or an intention-to-treat population. Without those definitions, the enrollment figure should not automatically be taken as the denominator for every endpoint. The adverse-event summary separately identifies 10 participants at risk for its listed categories, but the record does not explain how that set relates to each outcome analysis.
These reporting gaps limit assessment of endpoint completeness and the strength of any statistical inference. They do not show that data were missing or analyses were mishandled; they mean the relevant procedures 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 |
|---|---|---|---|
| Arm 1: MK-3475 | 1 | 10 | 10.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm 1: MK-3475 | 5 of 10 |
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 1: MK-3475 | 10 of 10 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1: MK-3475 |
|---|---|---|
| Congestive heart failure | Cardiac disorders | 1 of 10 |
| Pulmonary pretension | Respiratory, thoracic and mediastinal disorders | 1 of 10 |
| Hypotension | Vascular disorders | 1 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1: MK-3475 |
|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 9 of 10 |
| Nausea | Gastrointestinal disorders | 9 of 10 |
| Constipation | Gastrointestinal disorders | 8 of 10 |
| Peripheral sensory neuropathy | Nervous system disorders | 8 of 10 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 8 of 10 |
| Fatigue | General disorders | 7 of 10 |
| Cough | Respiratory, thoracic and mediastinal disorders | 7 of 10 |
| Alopecia | Skin and subcutaneous tissue disorders | 7 of 10 |
| Anemia | Blood and lymphatic system disorders | 6 of 10 |
| Blurred vision | Eye disorders | 6 of 10 |
Serious events with the highest arm-level rate: congestive heart failure (10.0%), pulmonary pretension (10.0%), hypotension (10.0%).
The registry lists 1 of 10 participants as affected by a serious adverse event and 10 of 10 as affected by other adverse events. It also records 5 deaths. These are separate descriptive counts in the posted safety information. The registry record does not report the cause of death or establish whether the deaths were related to MK-3475, surgery, adjuvant therapy, the underlying cancer, or another cause.
Congestive heart failure, pulmonary pretension and hypotension are the listed serious adverse event terms, each recorded at 10.0%. The registry does not report event-specific counts or clarify whether a participant could contribute to more than one term. The percentages should be read as recorded, without assuming a causal relationship or that the categories are mutually exclusive.
Seriousness, severity grade, and treatment attribution are different dimensions of safety reporting. The primary endpoint concerns any-grade treatment-related events meeting a frequency threshold; the serious-event listing does not provide that primary endpoint result. The registry record does not report enough detail to reconcile the serious-event terms with the primary endpoint count, or to determine the timing and duration of each event.
12. What the Result Does, and Does Not, Mean
The posted results provide limited descriptive safety information from a completed phase 1 study with 10 enrolled participants. They record serious adverse events in 1 of 10 participants, other adverse events in 10 of 10, and 5 deaths. Three serious event terms are listed, each at 10.0%. These observations describe the registry's safety record; they do not identify the cause of each event or establish whether an event was treatment-related.
The study's primary endpoint was defined around any-grade treatment-related adverse events experienced by at least 2 participants. The numerical result for that endpoint is not reported in the registry record. Progression-free survival is named as a secondary outcome, but its result is also not reported. There is no posted estimate with an uncertainty interval or statistical test for either outcome. As a result, the record does not support a quantified estimate of the primary endpoint or a comparative estimate of progression-free survival.
The single-group design is important to what can be concluded. Without a concurrent comparator, event counts cannot establish what would have occurred under a different treatment strategy. Because surgery and standard-of-care adjuvant therapy followed MK-3475 in the described sequence, the record also does not separate the contribution of each component to the observed safety events.
In general, a small study can identify observations that warrant further characterization, but the precision of event-frequency estimates depends on the amount and completeness of information. Here, the registry does not report a confidence interval or analysis population for the primary endpoint. The result should not be read as proof of benefit, lack of benefit, or comparative safety. It records a study design and selected safety information, while key clinical outcome estimates and their uncertainty are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates why a statistical reading begins with the design and endpoint definition rather than with isolated event counts. It is a completed phase 1 study of MK-3475 before surgery, with a single group and no concurrent control. Those features determine what the data can describe: observed safety information in the enrolled participants, rather than a randomized comparison of treatment strategies.
The primary endpoint is a participant-level safety criterion based on treatment-related events of any grade and a stated frequency threshold. The serious adverse event summaries are relevant but are not interchangeable with that endpoint. Keeping endpoint definitions separate prevents a serious-event count from being mistaken for the primary safety result, especially when that result is not numerically reported in the registry record.
The registry also demonstrates the importance of distinguishing a study's design rationale from a statistical result. The summary describes biological evaluation using pre-treatment and surgical tissue, while progression-free survival is listed as a secondary outcome. Yet no numerical result for the primary endpoint or progression-free survival is reported. A named outcome is not equivalent to a reported analysis, and a completed status does not fill in missing estimates.
Finally, the planning assumptions described in the record use a two-arm framework, whereas the study itself is single-group. This is a reminder that sample-size illustrations are conditional on design assumptions and should not be mistaken for the original justification or for evidence about the observed study. Statistical interpretation depends on matching the method to the question and clearly identifying which quantities are descriptive, inferential, or hypothetical.
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 enrollment of 10 and the single-group design limit what can be concluded from the posted record. There is no concurrent control group for comparison, and the design cannot separate events associated with MK-3475 from those associated with surgery, adjuvant therapy, the disease, or other factors. The registry does not report a numerical primary endpoint result, a progression-free survival result, or uncertainty estimates for either outcome.
The adverse-event information is also incomplete for detailed interpretation. Although counts and serious-event terms are listed, the registry record does not report event timing, duration, participant-level detail, or the cause of the 5 deaths. It does not explain whether serious-event terms overlap, or how the serious-event summary relates to treatment attribution and the primary endpoint's any-grade criterion.
Eligibility details, participant characteristics, analysis populations, and missing-data procedures are not reported in the registry record. The arm description ends mid-sentence, leaving some collection details unavailable. The record does not report a sample-size justification, a multiplicity strategy, interim analyses, or a statistical analysis plan. These items cannot be inferred from the study's phase, enrollment, or completed status.
These limitations concern what is documented in the registry record. They do not establish that procedures were absent from the protocol or that data were incomplete; those matters are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: MK-3475 Immunotherapy in Endometrial Carcinoma — NCT02630823.
- Registry record last updated 2025-01-03; status last verified 2024-11.
- Results first posted 2025-01-03.
- 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
NCT02630823 is a completed phase 1, single-group study sponsored by Washington University School of Medicine. The registry lists 10 participants enrolled and describes MK-3475 before surgical resection and standard-of-care adjuvant therapy. The study began on 2016-02-05, with primary completion on 2019-01-01.
The primary endpoint concerns any-grade treatment-related adverse events experienced by at least 2 participants, through 90 days following the last MK-3475 dose, approximately 56 weeks. The registry lists serious adverse events in 1 of 10 participants, other adverse events in 10 of 10, and 5 deaths. The primary endpoint's numerical result and the secondary progression-free survival result are not reported in the registry record. No statistical analyses are listed.