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 Pembrolizumab in Treating Patients With Advanced Merkel Cell Cancer (NCT02267603), a na phase 2 study. The primary outcome is Objective Response Rate (ORR) Defined as the Proportion of Patients Who Have Achieved Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02267603 |
| Phase | Phase 2 |
| Condition | Recurrent Merkel Cell Carcinoma, Stage III Merkel Cell Carcinoma AJCC v7, Stage IIIA Merkel Cell Carcinoma AJCC v7 |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced Merkel cell carcinoma, including recurrent disease and stage III or stage IV disease. The registry summary describes cancer that cannot be removed by surgery or controlled with treatment, or that has spread to other parts of the body. The primary endpoint description defines its analysis population as eligible participants who received at least one dose; the number meeting that definition is not reported in the registry record.
Intervention
Pembrolizumab, given intravenously over 30 minutes on day 1 and repeated every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Laboratory biomarker analysis is also listed as an intervention.
Comparator
There is no separate comparator arm. The study is registered as a single-group trial, with allocation listed as not applicable and no masking. Consequently, the design does not provide a randomized control group for estimating a treatment contrast.
Primary question
The primary endpoint asks what proportion of eligible participants who received at least one dose achieved a complete or partial response under RECIST version 1.1. The registry record defines this objective response rate but does not report the observed number or proportion of responders. The record therefore identifies the question and its response criteria, but does not establish the study’s observed response result.
3. Trial Design
This is a phase II study of pembrolizumab in patients with advanced Merkel cell carcinoma. The National Cancer Institute is the listed sponsor. The registry describes a single-group model, with allocation not applicable and no masking. There is no randomized comparator arm, so comparisons between treatment and control groups cannot be made within this trial.
The registry enrollment is 50. The study start date is 2014-11-25, and the primary completion date is 2018-02-06; its status is completed. These dates describe the registry record and do not, by themselves, specify the duration of observation for each participant. Participant-level follow-up duration is not reported in the registry record.
Participants in the treatment group receive pembrolizumab intravenously over 30 minutes on day 1, with treatment repeating every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. The treatment description notes that some participants with confirmed progression may continue treatment under stated circumstances, but the available registry wording is truncated before those circumstances are fully specified. The complete continuation criteria are not reported in the registry record.
The primary outcome is objective response rate according to RECIST version 1.1, with a timeframe of up to 3 years. Secondary outcomes include progression-free survival, duration of response, overall survival, and adverse events graded using NCI CTCAE version 5.0. The registry lists 7 outcome measures and 1 analysis. The full definitions and results for every listed outcome are not reported in the registry record. The design details establish how treatment was administered and which outcomes were of interest; they do not supply an observed treatment effect.
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 | Treatment (Pembrolizumab) |
|---|---|
| STARTED | 50 |
| COMPLETED | 6 |
| NOT COMPLETED | 44 |
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 | Treatment (Pembrolizumab) |
|---|---|---|
| Participants analysed | 50 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 40 |
| Age, Categorical: >=65 years | Participants | 10 |
| Sex: Female, Male: Female | Participants | 16 |
| Sex: Female, Male: Male | Participants | 34 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| 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 | 45 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 4 |
| Region of Enrollment: United States | participants | 50 |
6. Primary Endpoint
The registry lists the primary outcome as Objective Response Rate (ORR) Defined as the Proportion of Patients Who Have Achieved Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, measured over Up to 3 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is objective response rate, defined as the proportion of participants who achieve a complete response or partial response according to RECIST version 1.1. The registry specifies that the estimate uses eligible participants who received at least one dose of treatment as its denominator. It does not report the number of participants in that analysis population, the number of responders, or the resulting response rate.
General: A response endpoint classifies whether a participant’s disease meets predefined criteria for a complete or partial response. Combining those categories into an objective response rate gives a proportion of participants meeting either criterion during the specified assessment period. It is a measure of observed tumor response, not a direct measure of how long a response lasts, whether disease remains controlled, or how long participants live. Those are distinct questions, reflected in the separately listed duration of response, progression-free survival, and overall survival outcomes.
The registry gives the primary outcome timeframe as up to 3 years. It describes a binomial generalized linear model as a possible approach if substantial outcome data are missing, with available baseline predictors of missing outcomes included as covariates. The registry record does not report the observed primary endpoint result, the amount of missing response data, or whether that conditional missing-data analysis was needed. Accordingly, the endpoint definition is clear, but the response estimate and its precision cannot be assessed from the reported primary outcome information.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies objective response rate as the primary outcome and defines response using complete or partial response under RECIST version 1.1. However, it does not report the observed number of responders, the denominator used in the completed analysis, an estimated response rate, or a confidence interval. The principal efficacy result and its statistical precision therefore are not available in the registry record. No conclusion about the observed response frequency can be drawn from the endpoint definition alone.
The trial’s single-group structure is important for interpreting any outcome. Participants received pembrolizumab; the registered design has no randomized control group. An outcome observed in this group would describe what happened among participants in the study, but would not by itself estimate how their outcomes compare with a concurrent control group. Differences in patient characteristics, disease course, other care, or observation could not be separated from a treatment contrast using this design alone.
The registry describes a response assessment timeframe of up to 3 years. It also lists progression-free survival, duration of response, overall survival, and adverse events as secondary outcomes. Their definitions or numerical results are not reported in the registry record. A timeframe does not state how often assessments occurred, how complete follow-up was, or how many participants contributed data at each assessment. Those details are not reported in the registry record.
The enrollment is 50, and the safety information lists 50 participants at risk for the treatment group. Serious adverse events are reported for 22 participants, and other adverse events are reported for 50. Sixteen deaths are also listed. These figures describe the posted safety data; they do not establish that pembrolizumab caused any particular event or death. The registry record does not provide a causal attribution for these figures in the information available.
General: An estimate is more informative when accompanied by an interval that conveys the statistical uncertainty associated with the estimate. Without the response estimate and its interval, neither the observed response frequency nor its precision can be evaluated. The absence of a reported result is not evidence that the endpoint was zero, favorable, or unfavorable; it means the primary outcome result is not reported in the registry record. The same distinction applies to secondary outcomes whose numerical results are not included.
The registry describes a missing-data approach conditionally: if a substantial amount of data is missing, a maximum-likelihood parametric generalized linear model with binomial error and available baseline predictors of missing outcomes may be used for the response analysis. It does not say whether this condition occurred or provide the model estimate. Thus, the record contains an analysis description but not enough outcome reporting to assess the primary result or the effect of missing data on it.
9. Statistical Methods Explained
The primary outcome is a binary response classification: each participant is counted as having achieved complete or partial response, or not. The registry defines objective response rate as the number of responders expressed as a proportion of eligible participants who received at least one treatment dose. This is a participant-level proportion rather than a count of response assessments. The actual numerator, denominator, estimate, and uncertainty interval are not reported in the registry record.
What does a binomial model represent?
General: A binomial model is commonly used when an outcome records whether each participant has an event or meets a specified criterion. In this study description, the criterion is complete or partial response. The model relates the probability of that classification to any included predictors. The registry specifies a binomial error distribution for the generalized linear model it describes, but the result of such a model is not reported in the registry record.
The registry says that if a substantial amount of data is missing, analyses will be performed using parametric generalized linear models fit by maximum likelihood. The model for objective response rate will include available baseline predictors of missing outcomes as covariates. This is a conditional plan, not confirmation that substantial missingness occurred or that the model was used. The extent and pattern of missing response data, the predictors included, and any fitted estimates are not reported in the registry record.
Why can missingness matter?
General: If response status is unavailable for some participants, the estimated proportion may depend on which participants have observed outcomes and on the assumptions used to handle missing values. A model can use observed information and specified assumptions to estimate an outcome, but it does not reveal unobserved response statuses without assumptions. Assessing such an analysis requires details about missingness, the model, and the resulting estimates. Those details are not reported in the registry record beyond the conditional method description.
The analysis population is defined as eligible participants who received at least one dose. This differs conceptually from simply counting everyone enrolled: eligibility and treatment receipt determine the stated denominator. The registry enrollment is 50, but the number of participants who were eligible and received at least one dose is not reported in the registry record. It is therefore not possible to infer the primary endpoint denominator from enrollment alone.
What does the single-group structure imply?
General: In a single-group study, an outcome proportion describes the participants observed under the study’s treatment and assessment conditions. Without a concurrent randomized comparator, the design does not directly estimate a between-group treatment effect. A response rate, if reported, would need to be interpreted as a study-group observation rather than a randomized comparison. This trial is registered as single group, with allocation not applicable and no masking.
The registry also lists progression-free survival, duration of response, overall survival, and adverse events as secondary outcomes. These outcomes address different questions from the primary response proportion. General: time-to-event outcomes concern the timing of an event and can require methods that account for participants whose event has not been observed by the end of follow-up. The registry record does not provide the analysis details or results needed to describe how those secondary outcomes were analyzed.
The record lists 7 outcome measures and 1 analysis. Those counts do not identify how many statistical tests were performed, which outcomes were included in the analysis, or how inferential conclusions were coordinated. Multiplicity procedures are not reported in the registry record. Sample-size justification and interim analyses are also not reported in the registry record.
General: A confidence interval is a way to express uncertainty around an estimated quantity under a statistical model and its assumptions. A wider interval indicates less precision than a narrower interval, while the interval’s endpoints describe a range of values compatible with the analysis at its stated confidence level. No confidence interval for the primary response endpoint is reported in the registry record, so its precision cannot be evaluated from the posted primary outcome information.
The record includes a general description of planning illustrations based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that participant counts per arm would be used for non-time-to-event outcomes and total event counts for time-to-event outcomes. These are planning assumptions, not observed trial results, and this study is not a two-arm randomized comparison. The actual illustration values and the trial’s own sample-size rationale are not reported in the registry record. Such planning quantities would not be observed power or evidence that the study achieved a particular level of precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures, including objective response rate, progression-free survival, duration of response, overall survival, and adverse events. It records 1 analysis. The record does not explain how inferential testing across multiple outcomes was handled, whether any outcomes were prioritized beyond the designated primary endpoint, or whether adjustment for multiple comparisons was planned. Multiplicity procedures are not reported in the registry record, so the risk of interpreting several outcome tests without adjustment cannot be assessed from the available analysis description.
For the primary response endpoint, the registry identifies eligible participants who received at least one dose as the denominator. It does not report how many participants met these criteria, how many had an evaluable response, or the amount and pattern of missing outcome data. Enrollment is 50, but that alone does not establish the endpoint analysis population.
The registry describes a conditional missing-data method. If a substantial amount of data is missing, a parametric generalized linear model fit by maximum likelihood may be used, with binomial error and available baseline predictors of missing outcomes as covariates. The record does not indicate whether substantial missingness occurred, whether the model was used, which predictors were included, or how conclusions might change under other assumptions. Thus, a missing-data plan is described, but its implementation and impact are not reported in the registry record.
The primary endpoint description says responses to continued pembrolizumab will be chronicled and reported. The results of that reporting are not reported in the registry record. Analysis populations for the secondary outcomes, handling of withdrawals, and procedures for incomplete follow-up are likewise not reported. General: transparent reporting of these details helps readers distinguish the population originally enrolled from the population contributing to each outcome analysis.
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 |
|---|---|---|---|
| Treatment (Pembrolizumab) | 22 | 50 | 44.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Treatment (Pembrolizumab) | 16 of 50 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Treatment (Pembrolizumab) | 50 of 50 |
Most frequent serious adverse event terms
| Event term | Organ system | Treatment (Pembrolizumab) |
|---|---|---|
| Disease progression | General disorders | 8 of 50 |
| Dehydration | Metabolism and nutrition disorders | 4 of 50 |
| Aspartate aminotransferase increased | Investigations | 3 of 50 |
| Embolism | Vascular disorders | 3 of 50 |
| Small intestinal haemorrhage | Gastrointestinal disorders | 2 of 50 |
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | 2 of 50 |
| Fatigue | General disorders | 2 of 50 |
| Pyrexia | General disorders | 2 of 50 |
| Alanine aminotransferase increased | Investigations | 2 of 50 |
| Hyperglycaemia | Metabolism and nutrition disorders | 2 of 50 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Treatment (Pembrolizumab) |
|---|---|---|
| Fatigue | General disorders | 28 of 50 |
| Anaemia | Blood and lymphatic system disorders | 16 of 50 |
| Constipation | Gastrointestinal disorders | 14 of 50 |
| Upper respiratory tract infection | Infections and infestations | 14 of 50 |
| Diarrhoea | Gastrointestinal disorders | 11 of 50 |
| Alanine aminotransferase increased | Investigations | 11 of 50 |
| Decreased appetite | Metabolism and nutrition disorders | 11 of 50 |
| Hyperglycaemia | Metabolism and nutrition disorders | 11 of 50 |
| Cough | Respiratory, thoracic and mediastinal disorders | 11 of 50 |
| Pruritus | Skin and subcutaneous tissue disorders | 11 of 50 |
Serious events with the highest arm-level rate: disease progression (16.0%), dehydration (8.0%), aspartate aminotransferase increased (6.0%), embolism (6.0%), small intestinal haemorrhage (4.0%).
The posted safety figures list 50 participants at risk in the pembrolizumab treatment group. Serious adverse events are reported for 22 participants, and other adverse events are reported for 50 participants. The registry also lists 16 deaths. These are safety counts in the registry record; they should not be read as proof that treatment caused the events or deaths. Causal attribution is not reported in the registry record.
The most frequently listed serious adverse event terms include disease progression at 16.0%, dehydration at 8.0%, aspartate aminotransferase increased at 6.0%, and embolism at 6.0%. Small intestinal haemorrhage and upper gastrointestinal haemorrhage are each listed at 4.0%. The registry identifies adverse events as graded using NCI CTCAE version 5.0. The displayed terms and percentages describe reported serious events; they do not establish that each event was treatment-related.
General: Adverse-event categories can overlap at the participant level, so a participant may contribute to more than one event term. Seriousness and severity are also distinct concepts: an event’s serious classification does not, by itself, show its cause or establish how severe it was under every grading system. The registry record does not provide additional detail on event timing, duration, resolution, or attribution in the reported safety figures. Counts should therefore be interpreted as descriptions of reported events in this study group, not as a controlled estimate of comparative risk.
12. What the Result Does, and Does Not, Mean
The registry record establishes the study question, treatment schedule, primary endpoint definition, and some safety counts. It does not report the observed objective response rate, the response numerator or denominator, or an uncertainty interval. As a result, the principal efficacy outcome cannot be quantified from the registry record. An endpoint definition is not itself an outcome result, and the lack of a posted numerical result does not indicate any particular response level.
The study is a phase II, single-group trial of pembrolizumab in advanced Merkel cell carcinoma. A single group can describe outcomes among participants treated in the study, but it does not provide a randomized comparison against another treatment or a control condition. Even if an outcome estimate were available, it would not by itself distinguish the contribution of treatment from other influences on observed outcomes. This design limitation is central to interpreting any response or safety figure.
The posted safety data report serious adverse events for 22 participants, other adverse events for 50 participants, and 16 deaths among the treatment group. Several serious event terms and their percentages are listed. These are descriptive reports and are not a causal assessment. The record does not state that the events or deaths were caused by pembrolizumab, and the listed figures should not be used to make that attribution.
General: Statistical precision concerns how much uncertainty surrounds an estimate, while causal interpretation concerns whether an observed difference can be attributed to an intervention. These are separate issues. Here, the primary estimate and its precision are not reported, and the single-group design also lacks a randomized comparator. Therefore, neither the size and precision of the primary response result nor a comparative treatment effect can be evaluated from the registry record.
The registry describes secondary outcomes that could address durability, disease progression, survival, and safety, but their numerical results are not reported in the registry record. The completion status and study dates do not substitute for those results. The most defensible reading is limited to what is explicitly registered: a study designed to assess response and other outcomes, with the reported treatment and safety information, but without a posted primary response result.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why a clearly defined endpoint and a reported endpoint result are both necessary. The registry defines objective response rate as the proportion of eligible participants who received at least one dose and achieved complete or partial response by RECIST version 1.1. That definition specifies what is to be counted, but without the responder count, denominator, estimate, and uncertainty interval, readers cannot assess the observed response frequency or its precision.
The single-group design also illustrates the difference between describing an outcome and estimating a comparative effect. The study can be understood as a treatment-group investigation, but the registered design includes no randomized comparator. An observed result in one group would not on its own show how outcomes would have differed under another treatment or under no study treatment. This matters when interpreting both efficacy outcomes and adverse events.
The registry’s conditional description of a binomial generalized linear model is another important statistical detail. It specifies a possible approach if substantial response data are missing and identifies baseline predictors of missing outcomes as covariates. Yet the amount of missing data, actual model use, and model results are not reported. A stated method is not evidence that an analysis was conducted or that its assumptions were satisfied.
The posted safety counts offer descriptive information, but causal attribution and a controlled risk contrast are not reported. Similarly, the listed secondary outcomes signal questions about progression, response duration, survival, and adverse events, while their results and analysis details are not reported in the registry record. Distinguishing registered aims, reported data, and unavailable results is therefore essential to statistical interpretation of this study.
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 primary limitation for interpreting efficacy is that the registry record does not report the objective response result. It gives the endpoint definition and timeframe, but not the responder count, analysis denominator, estimate, or confidence interval. The number of eligible participants who received at least one dose is not reported, so the primary analysis population cannot be reconstructed from the registry enrollment of 50.
The study is single group, with allocation not applicable and no masking. There is no randomized control group for a direct comparison. The design therefore limits causal and comparative interpretation of any outcome estimate. The registry record does not report a sample-size justification, interim analyses, or multiplicity procedures. Although it describes general planning assumptions for sample-size illustrations, the actual values and the trial’s own design justification are not reported in the registry record.
The record’s missing-data approach is conditional on substantial missingness. It does not report whether that condition arose, how much response data were missing, which baseline predictors were used, or whether the described model was fitted. The record does not give enough information to assess the influence of missing outcomes on the primary analysis.
The primary outcome timeframe is up to 3 years, but participant-level follow-up, assessment timing, and completeness are not reported in the registry record. Secondary outcomes are named, but their numerical results and analysis details are not reported. The safety listing contains counts and selected event terms, but does not report causal attribution in the information available. Finally, the treatment description is truncated after noting that some participants with confirmed progression may continue treatment; the full criteria for continuation are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pembrolizumab in Treating Patients With Advanced Merkel Cell Cancer — NCT02267603.
- Registry record last updated 2023-07-05; status last verified 2023-06.
- Results first posted 2019-03-01.
- 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
NCT02267603 is a completed phase II, single-group study sponsored by the National Cancer Institute. It evaluates pembrolizumab in patients with advanced Merkel cell carcinoma, with registry enrollment of 50. The recorded start date is 2014-11-25, and primary completion is dated 2018-02-06. Treatment is described as intravenous pembrolizumab over 30 minutes on day 1, repeated every 21 days for up to 24 months in the absence of progression or unacceptable toxicity.
The primary endpoint is objective response rate by RECIST version 1.1, defined using complete or partial responses among eligible participants who received at least one dose. The outcome timeframe is up to 3 years. The observed response result and its precision are not reported in the registry record. The record lists secondary outcomes for progression-free survival, duration of response, overall survival, and adverse events.
For safety, 22 participants are listed with serious adverse events, 50 with other adverse events, and 16 deaths. These counts do not establish causal attribution. The registry describes a conditional missing-data analysis plan but does not report whether it was used. No randomized comparator is registered.