Study of a Melanoma Vaccine in Stage IIb, IIc, and III Melanoma Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of a Melanoma Vaccine in Stage IIb, IIc, and III Melanoma Patients (NCT01546571), a randomized phase 3 study. The primary outcome is Part B1: Recurrence Free Survival (RFS).

2. Clinical Question

The trial was designed to examine recurrence after surgery in a high-risk melanoma population. Its registered primary endpoint was Part B1 recurrence-free survival, while overall survival was listed as a secondary outcome. The registry record does not report the eligibility criteria in enough detail to characterize the enrolled population beyond the condition and post-resection context, nor does it report the primary endpoint results needed to assess the size or precision of any between-group difference.

3. Trial Design

The registry identifies this as a phase 3, randomized, triple-masked, parallel trial. Its official title describes a multicenter, double-blind, placebo-controlled, adaptive phase 3 trial. These descriptions indicate the broad design, but details of the randomization procedure, masking roles, allocation ratio, and adaptive features are not reported in the registry record.

The study tested POL-103A against POL-103A without API in Part B1. Part A included POL-103A at 40 micrograms per dose and 100 micrograms per dose, along with POL-103A without API. The registry does not describe the relationship between Part A and Part B1 in enough detail to reconstruct the full sequence of study decisions or treatment assignments. The official title identifies the study population as post-resection patients at high risk of recurrence.

Enrollment was 504. The recorded start date is 2012-05-01, and the primary completion date is 2021-04-29. The overall status is terminated. The primary endpoint applies to Part B1 only; the registry says the study was halted before Part B2. The timeframe listed for the primary outcome is 432 events or 8 years and 10 months. This is the stated endpoint timeframe, not a report that this event total was reached.

Overall survival was listed as a secondary outcome. The registry lists 14 outcome measures and one analysis, but the primary outcome is not reduced to a single arm-level comparison in the posted results. Specific analysis methods, stopping decisions, and the reasons for termination are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Overall Status of patients at the end of the study. This is applicable to Part B1 only. Study was halted prior to Part B2.

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 Part B1: Recurrence Free Survival (RFS), measured over 432 events or 8 years and 10 months.

The primary endpoint was Part B1 recurrence-free survival (RFS), described as a time-to-event outcome. RFS time begins from the earliest relevant date of recurrence or death. Recurrence is dated from the first date it is suspected, with confirmation by biopsy. For participants without recurrence or death, follow-up is censored at the date they were last assessed for recurrence without a diagnosis.

This endpoint is used to capture how long participants remain alive without a recorded recurrence, while accounting for participants whose follow-up ends before either event is observed. In general, time-to-event endpoints can retain information about the timing of events and handle differing follow-up durations through censoring. Censoring is not the same as confirming that no event will occur; it means that an event had not been diagnosed by the last recorded assessment.

The registry lists the timeframe as 432 events or 8 years and 10 months, and says the primary outcome applies to Part B1 only. That timeframe describes the stated event-driven endpoint horizon; it does not establish that the event target or follow-up duration was achieved. Although the outcome is defined as RFS time, the registry’s outcome-measure description identifies a count of participants. Numerical RFS estimates, event counts by arm, and a comparative effect estimate are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to study groups by chance. As a general statistical principle, it aims to reduce systematic differences between groups at the start of a trial, including differences that may not be measured. The registry classifies this study as randomized, but does not report the sequence-generation method, concealment procedure, or allocation ratio. Those details matter for evaluating how the random assignment was implemented. Randomization also cannot eliminate chance imbalances, prevent missing follow-up, or compensate for unavailable outcome results.

What do masking and a parallel design mean?

The registry lists triple masking and a parallel model, while the official title describes the study as double-blind. In a parallel design, participants remain in their assigned groups for the relevant comparison rather than crossing between treatments. Masking is intended to limit the influence of knowledge about assignment on participant experience, clinical care, or outcome assessment. The registry does not identify which roles were masked or explain the difference between its masking field and the title’s wording, so more specific claims about implementation are not possible.

How should recurrence-free survival be understood?

RFS is defined by the time until recurrence or death, using the earliest relevant event date. The registry specifies that recurrence is dated from the first suspicion later confirmed by biopsy. If neither recurrence nor death has occurred by the last assessment without a recurrence diagnosis, that observation is censored at that assessment. In general, censoring allows time-to-event analyses to include participants whose complete event time is not observed. Such analyses rely on assumptions about the censoring process; the specific assumptions and analysis method used for this trial are not reported in the registry record.

The outcome description identifies RFS time, but the registry also characterizes its measure as a count of participants. These are related but not interchangeable representations: a participant count alone does not convey when events occurred or how follow-up was handled. The posted record does not give the arm-level event data or a survival estimate, so no time-to-event curve or hazard comparison can be described from the registry entries.

What does the event-driven timeframe imply?

The primary outcome timeframe is stated as 432 events or 8 years and 10 months. In general, an event-driven design plans around the accumulation of a target number of outcome events, because event information is central to estimating a time-to-event contrast. The registry does not say whether the event target was reached, how the time limit was applied, or what analysis was performed when the trial stopped. It also does not report interim analysis procedures or stopping boundaries. The timeframe should therefore be read as the stated endpoint horizon, not as a result or proof of completion.

What do the planning illustrations mean?

Planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They use the observed effect as a basis for considering effects at stated fractions of that effect. For time-to-event outcomes, the illustrations express sample size as the total number of events using the Schoenfeld approach; other illustrations express participants per arm. These are planning calculations, not observed power and not the trial’s reported design justification. No sample-size justification or detailed protocol calculation is reported in the registry record. Without numerical values for the illustration rows, no particular event target or participant requirement beyond the primary timeframe can be inferred from them.

Why are estimates and uncertainty important?

A treatment-effect estimate describes the observed contrast between groups, while a confidence interval describes the range of values reasonably compatible with the data under the analysis assumptions. In general, a wider interval indicates less precision, and an interval that includes values on both sides of no difference may leave the direction or size uncertain. A p-value addresses compatibility with a specified null hypothesis under a statistical model; it does not measure clinical importance or the probability that a hypothesis is true. None of these numerical quantities for the primary RFS comparison are reported in the registry record.

The trial is described as adaptive in its official title, but adaptation rules, decision points, and methods for controlling error rates are not reported. Those details can matter when a study changes its course in response to accumulating data. The registry also does not report the primary analysis model, covariate adjustment, stratification factors, or handling of protocol deviations. As a result, the statistical methods actually used for the primary comparison cannot be reconstructed from the record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists overall survival as a secondary outcome and reports 14 outcome measures. It does not describe how many hypotheses were formally tested, which outcomes were included in confirmatory testing, or whether any adjustment was made for multiple comparisons. When many outcomes or analyses are examined, the chance of at least one apparently unusual result can increase; methods such as hierarchical testing or multiplicity adjustment can address that issue. Whether such methods were used is not reported in the registry record. The official title uses the word adaptive, but the adaptation procedures and their relationship to multiplicity control are also not reported.

The primary outcome applies to Part B1 only, and the record states that the study was halted before Part B2. It does not report the analysis populations, such as whether the primary comparison included all randomized participants or a subset, nor does it describe exclusions or protocol deviations. The record lists one analysis, but does not provide enough detail to identify its population, model, or role in the planned analysis strategy.

For RFS, the endpoint definition includes censoring participants who have neither recurrence nor death by their last assessment without a recurrence diagnosis. This describes how an observation may be censored, but does not report how many participants were censored, why follow-up ended, or whether missing assessments were handled in other ways. Missing-data methods, sensitivity analyses, and assumptions about loss to follow-up are not reported in the registry record. These details are important because incomplete follow-up can affect the precision and interpretation of a time-to-event comparison.

Interim analyses, stopping rules, and the handling of the trial’s termination are not reported. Without those details, the posted record does not support an assessment of whether the final analysis followed a prespecified plan or how decisions during the trial may have affected inference.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists five group entries across Part A and Part B1. The serious-adverse-event field reports 0 affected participants in every listed group. The numbers at risk in those entries are 52 for Part A POL-103A 40 micrograms per dose, 52 for Part A POL-103A 100 micrograms per dose, 53 for Part A POL-103A without API, 230 for Part B1 POL-103A, and 117 for Part B1 POL-103A without API.

The other-adverse-event field reports 48 affected participants in Part A POL-103A 40 micrograms per dose, 51 in Part A POL-103A 100 micrograms per dose, 51 in Part A POL-103A without API, 212 in Part B1 POL-103A, and 113 in Part B1 POL-103A without API. The deaths field lists 12, 12, 6, 29, and 20, respectively. These are posted counts for the listed groups, not rates or adjusted comparisons.

The record does not describe the event definitions, severity categories beyond the serious-event field, timing, relatedness assessments, or overlap between participants with events and deaths. It also lists no top serious-event terms. A zero in the serious-adverse-event field should be read as the count recorded for that group, not as proof that no safety concerns occurred. Differences between raw counts cannot be interpreted without accounting for group size, follow-up, and event ascertainment; the registry does not report a comparative safety analysis.

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

The record identifies a randomized phase 3 trial of POL-103A in post-resection melanoma patients at high risk of recurrence and defines Part B1 RFS as its primary endpoint. It also reports overall survival as a secondary outcome and posts safety counts for Part A and Part B1 groups. These registry entries describe the study’s scope and its recorded outcome framework.

However, the registry record does not report numerical RFS results by arm, a treatment-effect estimate, a confidence interval, or a p-value. It therefore does not establish the direction, magnitude, or precision of the primary comparison. The absence of those results in the registry record is not evidence that there was no effect, just as the trial’s design and endpoint definition are not evidence that an effect occurred.

The stated timeframe of 432 events or 8 years and 10 months does not show that either condition was met. The study status is terminated, and the record says it was halted before Part B2, but does not explain why. Without reported follow-up, event totals, or analysis details, the amount of information available for the Part B1 comparison cannot be assessed.

The safety counts are also limited. They do not provide event rates, severity details beyond the serious-event field, or adjusted comparisons. Counts of deaths are reported, but their relationship to RFS, cause, and treatment assignment is not described in the registry record. The posted information is therefore insufficient to determine the balance of safety outcomes between groups.

In general, a trial’s result is interpreted by considering the estimate, its uncertainty, the analysis population, follow-up, missing data, and the prespecified statistical plan. Several of these elements are not reported in the registry record. The appropriate conclusion is consequently narrow: the record describes the intended trial comparison and some safety counts, but does not provide the numerical primary outcome evidence required to characterize the comparative RFS result.

13. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint definition is essential for interpreting a clinical comparison. Recurrence-free survival combines recurrence and death as events and specifies how recurrence is dated and how participants without an event are censored. Those rules define what the outcome means and how follow-up contributes to an analysis. Without them, a reported count or time-to-event estimate could be difficult to interpret consistently.

It also highlights the distinction between a planned event-driven timeframe and a reported outcome. The registry states 432 events or 8 years and 10 months, but does not say whether the event target was reached. A target describes how the study was framed; an observed event count describes what occurred. Keeping those concepts separate prevents a design feature from being mistaken for evidence about the result.

The official title identifies the study as adaptive, yet the record does not detail its adaptation rules, stopping decisions, or error-rate procedures. Statistically, those details are important because planned changes based on accumulating data can affect how confirmatory evidence is evaluated. Their absence limits assessment of how the design operated in practice, especially alongside the recorded termination and the halt before Part B2.

Finally, the registry makes the difference between descriptive safety counts and a comparative safety analysis visible. Counts alone do not account for follow-up or establish a treatment-related contrast. The missing primary estimates and analysis details demonstrate why transparent reporting of effect estimates, uncertainty, populations, missing data, and analysis plans is needed to support a statistical interpretation.

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 central limitation is that numerical results for Part B1 RFS are not reported in the registry record. There are no arm-specific estimates, event counts, confidence intervals, or p-values in the registry entries, so the primary comparison cannot be quantified. The record’s description of RFS and its endpoint timeframe do not replace those results.

The study is marked terminated, and the record states that it was halted before Part B2. Reasons for termination, the status of Part B1 follow-up, whether the event target was met, and the timing of the halt are not reported in the registry record. These omissions make it difficult to assess the completeness of outcome observation or the relationship between planned and completed study activities.

The official title calls the design adaptive, but operational details are not reported. Neither are the analysis model, allocation ratio, stratification factors, analysis populations, interim analyses, stopping rules, or multiplicity procedures. The registry also does not explain the discrepancy between its triple-masked design field and the double-blind wording in the official title. These gaps restrict evaluation of the analysis plan and its implementation.

The safety information is limited to counts for serious adverse events, other adverse events, and deaths in the listed groups. Event definitions, timing, severity detail, relatedness, and comparative methods are not reported. The record does not provide enough information to evaluate the representativeness of the enrolled population beyond melanoma and the post-resection context in the official title. These limitations are specific to the available registry record and should not be treated as evidence for or against an effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of a Melanoma Vaccine in Stage IIb, IIc, and III Melanoma Patients — NCT01546571.
• Registry record last updated 2025-10-24; status last verified 2025-09.
• Results first posted 2025-10-24.
• 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.

18. Record Summary

NCT01546571 is a randomized, triple-masked, parallel phase 3 trial of POL-103A in post-resection melanoma patients described as being at high risk of recurrence. The official title describes a multicenter, double-blind, placebo-controlled, adaptive trial. Part B1 compares POL-103A with POL-103A without API; Part A lists two POL-103A dose groups and a group without API.

Enrollment was 504. The primary outcome was Part B1 recurrence-free survival, defined using recurrence or death, with censoring at the last assessment without a recurrence diagnosis for participants without either event. The stated timeframe was 432 events or 8 years and 10 months. Overall survival was listed as a secondary outcome. The record says the study was terminated and halted before Part B2.

Numerical primary-outcome estimates and comparative statistical results are not reported in the registry record. Safety fields list counts for serious adverse events, other adverse events, and deaths across five group entries, but do not include a comparative safety analysis.