Neoadjuvant Lenvatinib Plus Pembrolizumab in Merkel Cell Carcinoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neoadjuvant Lenvatinib Plus Pembrolizumab in Merkel Cell Carcinoma (NCT04869137), a na phase 2 study. The primary outcome is Pathological Complete Response.

2. Clinical Question

3. Trial Design

This is a phase 2, single-group trial of neoadjuvant lenvatinib plus pembrolizumab in resectable Merkel cell carcinoma. The registry record lists an enrollment of 26. It describes one treatment group and no randomized allocation; masking is listed as none. Thus, the design is not a randomized comparison, and any outcome observed in the treatment group cannot by itself estimate how the same participants would have fared under a different treatment.

The treatment description specifies two cycles of the combination over 6 weeks, followed by planned resection within 2-4 weeks after cycle 2. The primary endpoint is pathological complete response, determined by examination of tissue after treatment and resection, with a listed timeframe of 1 year. Secondary outcomes include progression-free survival and the percentage of patients able to complete both neoadjuvant cycles and planned surgical resection.

The record lists a start date of 2021-05-28, a primary completion date of 2025-09-13, and a status of active, not recruiting. These registry entries describe the trial's status and schedule; they are not evidence that the primary endpoint has been analyzed. The registry record lists three outcome measures and no analyses. It does not report a primary endpoint estimate, a confidence interval, or a test of the endpoint.

Details such as eligibility criteria beyond the stated resectability, the planned analysis population, and the statistical analysis plan are not reported in the registry record. Since the trial has no control arm, the design can describe outcomes among treated participants but cannot establish a treatment contrast within the trial.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Pathological Complete Response, measured over 1 year.

Pathological complete response is the primary endpoint. The registry describes it as a percentage of participants and says it will be determined by a pathologist's examination of tissue after neoadjuvant treatment and resection. The listed timeframe is 1 year. The record does not give more detailed criteria for classifying tissue findings as a complete response.

In general, a pathological endpoint uses examination of tissue rather than relying only on a clinical assessment or imaging result. After surgery, tissue examination can provide a direct assessment of whether the features being evaluated are present in the examined specimen. For a neoadjuvant trial, this makes pathological response a way to describe tumor findings after the pre-surgical treatment course. That general rationale does not establish how the endpoint was operationalized in this trial beyond the registry's description.

A percentage endpoint requires both a defined response classification and a denominator of participants assessed. The registry record does not report the number classified as having a pathological complete response, the number assessed for this endpoint, or an estimated percentage. It therefore does not support a conclusion about the frequency of response or the precision of that estimate.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary outcome at the participant level: a participant is classified according to whether pathological complete response is present. The registry expresses the endpoint as a percentage of participants. The record does not report the number of participants meeting the response definition, the number assessed, or an analysis estimate. The statistical concepts below explain how such an endpoint is generally described; they are not a report of analyses performed in this trial.

How is a response percentage interpreted?

In general, a response percentage is calculated from the number of participants classified as responders relative to a defined analysis denominator. The numerator and denominator need to be clear: the numerator identifies participants who meet the response criteria, while the denominator identifies the participants included in the endpoint analysis. For a post-surgical pathological endpoint, the analysis plan also needs to specify how participants without an evaluable specimen are treated. Those details are not reported in the registry record, and no response percentage is posted.

A percentage is an estimate from the participants assessed, not a guarantee of the underlying response frequency in a broader population. A confidence interval is a range of values reflecting sampling uncertainty under stated assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. The registry record does not report a confidence interval for pathological complete response, so the precision of any response estimate cannot be assessed.

What does the single-group design allow?

In general, a single-group study can describe what happened among its participants. It cannot provide a randomized estimate of the contrast between the study treatment and an alternative, because the alternative group is absent. Treatment assignment is not randomized in this record, and there is no listed comparator. Differences between this group's outcomes and outcomes observed elsewhere could reflect differences in participant characteristics, clinical care, outcome definitions, follow-up, or other factors. The registry record does not provide a basis for adjusting or accounting for such differences.

Masking is listed as none. For the primary endpoint, the registry says that a pathologist examines tissue, but it does not report whether the pathologist was blinded to treatment or provide procedures for assessment. The design information therefore does not establish whether assessment was conducted without knowledge of treatment.

What can be said about planning calculations?

The registry record does not report a sample-size justification or the statistical plan used to design the trial. The available planning illustration is described as separate from the trial's own design. Its stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. Those assumptions do not describe this single-group trial, which has no two-arm allocation in the registry record. No numerical planning results are reported in the available record, and such illustrations should not be interpreted as observed power or as evidence about trial outcomes.

More generally, sample-size calculations depend on the outcome, the effect considered meaningful for planning, the variability or event frequency assumed, the statistical procedure, and the desired operating characteristics. If those assumptions do not match the actual design or analysis, a planning calculation cannot be read as a finding from the study. The registry does not report the assumptions used by the investigators for the trial's own enrollment target.

What role would a statistical test play?

A statistical test evaluates data relative to a specified hypothesis and analysis method. A p-value, when reported, describes how compatible the observed data are with that hypothesis under the test's assumptions; it is not the probability that the hypothesis is true. A test result does not convey the size or clinical importance of an effect by itself. For a single-group response endpoint, the hypothesis and reference value would need to be specified to interpret a test. The registry record does not report a hypothesis, reference value, or primary endpoint test.

For a percentage endpoint, binomial methods are often considered because each participant is classified into one of two outcome categories. The suitability of a particular interval or test depends on the data and design. No method for calculating an interval or testing the primary endpoint is reported in the registry record, so no specific inferential procedure should be attributed to this trial.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lenvatinib Plus Pembrolizumab")
n      <- c(26)
events <- c(15)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lenvatinib Plus Pembrolizumab  26  15  57.7  36.9  76.6  38.9  74.5  38.8  74.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists pathological complete response as the primary outcome and names progression-free survival and the percentage of patients able to complete both neoadjuvant cycles and planned surgical resection as secondary outcomes. It lists three outcome measures and no analyses. There are no reported estimates or tests for these outcomes in the registry record.

When a study evaluates several outcomes or performs multiple tests, multiplicity refers to the increased chance of obtaining a statistically notable result simply because many hypotheses were examined. In general, a statistical analysis plan may designate a primary endpoint, define which comparisons or timepoints are tested, and specify whether and how testing is adjusted. The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or the number of planned tests. No adjustment should be assumed.

Missing outcome data can also affect interpretation. For this endpoint, participants may not have an evaluable pathological assessment for reasons such as not completing surgery, but the record does not report whether this occurred or how such cases would be classified. It does not specify whether the primary endpoint analysis would include all enrolled participants, only participants who underwent surgery, or another population. It also does not report rules for incomplete follow-up for progression-free survival or the treatment-completion outcome.

These omissions mean the denominator, missing-data assumptions, and analysis population for the primary endpoint are unknown. In general, different rules for participants without an observed endpoint can produce different estimates. The registry record does not provide enough detail to determine which rule was used or to assess the effect of missing data on any result.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: atrial fibrillation (3.8%), death nos (3.8%), sudden death nos (3.8%), lung infection (3.8%), hyponatremia (3.8%).

For the lenvatinib plus pembrolizumab group, the registry lists 26 participants at risk for serious adverse events and 5 participants affected. It lists 26 at risk for other adverse events and 26 affected. The record also lists 3 deaths. These are safety counts, separate from the primary pathological complete response endpoint.

The listed serious adverse event terms include Atrial Fibrillation, Death NOS, Sudden death NOS, Lung infection, Hyponatremia, and Muscle weakness lower limb, each reported as 3.8%. The registry does not provide additional details in this record about timing, severity beyond the serious-event classification, duration, or whether events in different categories occurred in the same participant. The term Death NOS should be read as the recorded term, not as an explanation of cause.

A serious adverse event count describes events classified as serious in the registry; an other-adverse-event count is a separate category. The counts do not establish that an event was caused by treatment. The registry record does not report attribution for the listed events or deaths, nor does it provide a comparison group. They should therefore be read as the safety information recorded for this group, not as a causal comparison.

13. What the Result Does, and Does Not, Mean

The registry record establishes that this phase 2 study was designed to evaluate neoadjuvant lenvatinib plus pembrolizumab in participants with resectable Merkel cell carcinoma. It specifies a pathological complete response endpoint assessed by examination of tissue after treatment and resection, and it describes a treatment course followed by planned surgery. These details clarify the clinical question and the kind of outcome the trial intended to measure.

The record does not report the primary endpoint result. There is no posted response count, percentage, confidence interval, or inferential analysis. Therefore, the registry information does not establish how often pathological complete response occurred in the trial participants, or how precisely that frequency was estimated. An enrollment figure is not a substitute for an endpoint denominator or response count.

The design also limits what a result from this trial could say. Because it is a single-group study with no comparator, an observed outcome would describe the treated group rather than estimate a randomized difference from another approach. The record cannot support a causal comparison between the combination and an alternative treatment.

The safety entries provide counts of serious adverse events, other adverse events, and deaths in the treatment group. They do not, on their own, establish whether treatment caused any event or whether the recorded counts are higher or lower than would occur under another approach. Causal attribution and comparative safety results are not reported in the registry record.

In general, statistical interpretation depends on the outcome definition, analysis population, missing-data rules, and uncertainty around estimates. Several of these details and the outcome analyses are not reported. The sound conclusion is therefore limited: the registry describes the trial's design and planned endpoint, but it does not post the efficacy analysis needed to quantify the primary outcome.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly stated clinical endpoint and the availability of results for that endpoint. The registry identifies pathological complete response as the primary outcome and explains that it is assessed in tissue after neoadjuvant therapy and resection. Yet no endpoint analysis is listed. A named outcome alone does not tell readers the observed response frequency or its uncertainty.

The single-group design is also important to interpretation. It can describe outcomes among participants receiving the combination, but there is no concurrent randomized group to provide a treatment contrast. This affects the type of conclusion that could be drawn even if endpoint results were posted. Statistical precision around a single-group percentage would not resolve the absence of a comparator or establish a causal effect.

The registry record also highlights why denominators and analysis populations matter. The enrollment is listed as 26, while the primary endpoint requires a pathological assessment after resection. The record does not report how many participants had an evaluable specimen or how participants without an assessment would be handled. Without those details and an outcome count, a percentage cannot be interpreted.

Finally, the safety counts and event terms require a separate reading from efficacy results. They describe recorded safety outcomes but do not state attribution or provide a control group. Keeping these different statistical questions separate helps prevent safety counts, design details, or planning assumptions from being mistaken for evidence about the primary endpoint.

15. 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 of the available registry information is the absence of posted outcome analyses. The primary endpoint is described, but its response count, percentage, and precision are not reported. The record lists three outcome measures and no analyses, so the clinical outcome question cannot be answered from the recorded results.

The single-group design has no randomized comparator. It can describe outcomes in the treated group but cannot estimate a randomized difference between the combination and another treatment. This limitation applies to interpretation of both efficacy and safety comparisons.

The registry record does not report the endpoint analysis population, the denominator used for pathological complete response, or how participants without an evaluable pathological assessment would be handled. It also does not provide detailed pathological response criteria beyond examination of tissue after neoadjuvant treatment and resection. These omissions prevent assessment of how the endpoint was operationalized and how missing observations might affect an estimate.

The record does not report the statistical analysis plan, a sample-size justification for the trial, the planned inferential methods, or a multiplicity strategy. It also does not state whether outcome assessors were blinded. These details should not be inferred from the general planning assumptions listed for sample-size illustrations, which do not describe the single-group design.

For safety, the record gives counts and selected serious adverse event terms but does not report attribution, timing, or comparative data. The listed deaths therefore cannot be interpreted as treatment-caused or compared with an alternative. The registry status and dates provide trial context but do not replace completed outcome analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neoadjuvant Lenvatinib Plus Pembrolizumab in Merkel Cell Carcinoma — NCT04869137.
• Registry record last updated 2026-04-08; status last verified 2026-03.
• Results first posted 2026-04-08.
• 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.

19. Record Summary

The registry record describes a phase 2, single-group trial of neoadjuvant lenvatinib plus pembrolizumab for resectable Merkel cell carcinoma, with an enrollment of 26. It lists two treatment cycles over 6 weeks followed by planned resection within 2-4 weeks after cycle 2. Pathological complete response is the primary endpoint, assessed by pathologist examination of tissue after treatment and resection, with a listed timeframe of 1 year.

Secondary outcomes include progression-free survival and completion of both neoadjuvant cycles and planned surgery. The record lists three outcome measures and no analyses, and does not report the primary endpoint result. Safety entries include 5 participants with serious adverse events among 26 at risk, 26 with other adverse events among 26 at risk, and 3 deaths. The record does not report causal attribution or a comparator group.