Phase IIB TL + YCWP + DC in Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase IIB TL + YCWP + DC in Melanoma (NCT02301611), a randomized phase 2 study. The primary outcome is Disease Free Survival Assessment.

2. Clinical Question

3. Trial Design

The registry identifies this as a phase IIb melanoma trial with randomized allocation and triple masking. Its official title describes a prospective, randomized, blinded, placebo-controlled study of autologous tumor lysate, yeast cell wall particles, and dendritic cells, with an embedded phase I/IIa trial of a tumor lysate particle-only vaccine. The record status is completed. The listed start date is 2015-01, and primary completion is recorded as 2022-05-11.

The main comparison is described as active TLPLDC vaccine versus unloaded yeast cell wall particles with autologous dendritic cells as control. The record also lists TLPO and TLPLDC-G adverse-event groups. It labels the trial model as SINGLE GROUP even though allocation is listed as randomized and the arm descriptions name treatment and placebo. These registry entries are not fully aligned, and the record does not explain the discrepancy or how the embedded study relates to the main randomized comparison.

The trial enrolled 187 participants, but the registry material does not provide a complete account of assignment by arm, participant flow, or the analysis populations used for the primary outcome. Those details are important for understanding how the randomized design was implemented and who contributed to the outcome analyses. They are not reported in the registry record.

The vaccine summary describes an autologous approach intended to combine a patient's tumor antigens with dendritic cells. It states that the vaccine is injected intradermally monthly x 3, followed by boosters at 6, 12, and 18 months. The planned primary endpoint is disease-free survival at 24 months. The registry description says an interim analysis would compare median disease-free survival six months after the final patient was enrolled. Whether that analysis occurred, and what methods it used, 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

Analysis population for the primary outcome, as defined in the registry: Number of participants remaining at displayed timepoints

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 Disease Free Survival Assessment, measured over 24 months.

The primary endpoint is disease-free survival (DFS) at 24 months, compared between the vaccinated and control groups after the final enrolled patient completes two years of follow-up. The registry describes the outcome as the number of participants remaining at displayed timepoints. It does not provide the actual primary outcome values or a statistical comparison in the posted results.

In general, disease-free survival is a time-to-event outcome: it concerns how long participants remain without a defined disease event after a specified starting point. Such outcomes can be useful when the clinical question concerns recurrence over follow-up, rather than only a participant's status at a single visit. Interpretation depends on the event definition, the time origin, follow-up completeness, and the way censoring is handled. Those details are not reported in the registry record.

The description also refers to an interim comparison of median DFS. A median is a summary of the event-time distribution, but it does not by itself show the full pattern of outcomes over time or the precision of a comparison. No median estimates, confidence intervals, or inferential results are reported. The registry outcome is categorized as a participant count, and the result reduction indicates that the primary outcome has several categories or time points rather than one comparison. Without the displayed values and analysis details, the endpoint's observed magnitude and uncertainty cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Random allocation is intended to create groups that are comparable, on average, with respect to factors that can affect outcomes. In a well-reported randomized trial, the analysis can then estimate the effect of assignment to the intervention relative to assignment to control, subject to issues such as adherence, missing data, and the chosen analysis population. The registry lists randomized allocation, but does not report the allocation procedure, concealment details, or a primary-outcome analysis. These omissions prevent assessment of how randomization was implemented or how it was reflected in the analysis.

What does triple masking mean?

The registry labels masking as triple. Masking generally means that specified people involved in a trial are kept unaware of treatment assignment, which can reduce the chance that expectations affect care, outcome assessment, or reporting. The record does not identify which roles were masked, how masking was maintained, or whether it remained intact. The label alone cannot establish those details.

How should disease-free survival be analyzed?

In general, time-to-event methods account for both the timing of an event and the fact that some participants may have incomplete observation when follow-up ends. Participants without a recorded event by the end of their observed follow-up may be censored rather than treated as if they had an event. The validity of such an analysis depends on a clear event definition and appropriate handling of censoring. The registry states DFS at 24 months and mentions median DFS for an interim analysis, but does not report the event definition, time origin, censoring approach, model, or estimates.

A fixed-time survival summary and a comparison of full event-time distributions answer related but not identical questions. The former focuses on status at a designated time; the latter uses the timing of events across follow-up. General interpretation should account for this distinction. The registry description says the outcome is represented by participants remaining at displayed timepoints, and the posted results are not reduced to one comparison because there are several categories or time points. Without outcome values and methods, it is not possible to identify the exact estimand or reconstruct a valid comparison.

What does a confidence interval contribute?

In general, a confidence interval expresses the statistical uncertainty around an estimated effect under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while an interval that includes values corresponding to no difference may leave the direction or presence of an effect unresolved. It is not a guarantee that the true effect lies within the interval, and it does not address biases arising from design or missing data. No primary-outcome confidence interval is reported in the registry record.

How should p-values be read?

In general, a p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions hold. It does not measure the probability that a treatment is effective, the size of an effect, or the chance that a result is due to bias. The registry record does not report a primary-outcome p-value or the statistical test used. Consequently, no significance claim can be assessed from the posted primary results.

What does an interim analysis imply?

The registry description says an interim analysis would compare median DFS six months after the final patient was enrolled. Interim analyses examine accumulating data before the final analysis and can raise issues about repeated testing and decision thresholds. In general, a prespecified statistical plan may address these issues. The plan, any adjustment for interim looks, whether the analysis was conducted, and its results are not reported in the registry record. It would be inappropriate to infer a particular interim-testing method.

How should planning illustrations be understood?

In general, sample-size calculations are planning tools based on assumptions about the target effect, variability or event rate, allocation, and error thresholds. An illustration calculated from an observed effect is not the same as the trial's prospective design justification, and it is not observed power. The registry record states that any planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. It also distinguishes total event counts for time-to-event planning from participants per arm for other outcomes. The record does not report the trial's own sample-size justification, and no primary effect estimate is available in the posted results to assess such an illustration.

Over-dispersion is a general statistical concern when observed counts vary more than a model assumes; ignoring it can make uncertainty appear too small. Its relevance depends on the outcome and model. The registry does not report a model for the primary endpoint or an analysis that requires a count-distribution assumption, so no trial-specific claim about over-dispersion can be made.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary DFS assessment at 24 months and an interim comparison of median DFS. It does not report a statistical analysis plan, identify the complete set of planned hypotheses, or explain how any repeated testing would be handled. In general, testing multiple outcomes, timepoints, subgroups, or interim looks can increase the chance of a false-positive result if the analysis does not account for multiplicity. The record does not establish which procedures, if any, were planned or applied.

The primary outcome is described as participants remaining at displayed timepoints, while the result reduction indicates several categories or time points rather than one comparison. The posted record does not provide the timepoint-specific outcome values or explain how a single primary conclusion would be selected from them. Neither an interim result nor a final primary comparison is reported.

Missing-data methods are also not reported in the registry record. For a time-to-event endpoint, incomplete follow-up and censoring can affect estimates; for a fixed-time status, missing outcome assessments may require explicit handling. The record does not state the amount or pattern of missing primary-outcome data, assumptions about missingness, or sensitivity analyses.

The analysis populations are not reported in the registry record. In general, an analysis based on randomized assignment and one based on treatment received can answer different questions. The record does not identify which participants were included in the primary analysis, whether exclusions occurred, or how deviations from assigned treatment were handled. Thus neither multiplicity control nor the robustness of the primary analysis can be evaluated from the posted information.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (6.4%), portal vein thrombosis (4.9%), wound infection (4.9%), cough (4.3%), intracranial hemorrhage (4.3%).

The registry reports serious adverse-event counts as participants at risk and participants affected. For Treatment TLPLDC, it lists 47 at risk and 4 affected; for Placebo, 41 at risk and 6 affected; for Treatment TLPO, 43 at risk and 7 affected; and for Treatment TLPLDC-G, 56 at risk and 6 affected. For other adverse events, the corresponding at-risk and affected counts are 47 and 24 for Treatment TLPLDC, 41 and 14 for Placebo, 43 and 15 for Treatment TLPO, and 56 and 13 for Treatment TLPLDC-G. Deaths are listed as 14, 6, 6, and 1 for those groups, respectively.

The registry also lists serious adverse-event terms with percentages: Sepsis, 6.4%; Portal vein thrombosis, 4.9%; Wound infection, 4.9%; Cough, 4.3%; Intracranial hemorrhage, 4.3%; and Muscle weakness, 2.4%. The record does not specify the denominator or clearly assign these term percentages to individual groups. They should not be treated as arm-specific rates.

These counts describe registry entries, not necessarily events caused by treatment. The record does not report event definitions, attribution, exposure-adjusted analyses, or enough follow-up detail for a full comparative safety assessment. Death counts are not themselves evidence of cause or treatment effect.

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

The registry record establishes that a randomized, triple-masked phase IIb study was conducted to assess a personalized dendritic-cell vaccine approach in resected stage III and stage IV melanoma. It identifies the intended primary question as a comparison of disease-free survival at 24 months between vaccinated and control groups. It also describes an interim median-DFS comparison and lists adverse-event information for multiple groups.

What the record does not establish is whether the active vaccine improved, worsened, or had no effect on disease-free survival. No primary endpoint values, effect estimate, confidence interval, or p-value are reported in the posted results. Without these, the size and precision of the primary comparison cannot be evaluated. Completion status and enrollment do not provide the missing outcome evidence.

The record's adverse-event counts can be read as descriptive entries, but they do not determine whether differences between groups are attributable to treatment. The additional TLPO and TLPLDC-G groups, alongside the randomized treatment and placebo descriptions, also make it important not to assume that every listed group belongs to the same primary comparison. The record does not explain those relationships in sufficient detail.

In general, trial results support conclusions only when the outcome definition, analysis, uncertainty, follow-up, and participant inclusion are adequately reported. Here, key information about the primary analysis, missing data, and analysis populations is not reported in the registry record. The sound interpretation is therefore about the study's stated objective and limitations of its available registry reporting, not a conclusion about vaccine efficacy or safety.

13. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly stated randomized clinical question and the limited primary-outcome information in the registry record. Randomized allocation and triple masking are relevant design features, but they do not by themselves provide an estimate of the effect on DFS. Readers need the outcome data and analysis to understand what the trial found and how uncertain that finding is.

The record also combines descriptions of a main phase IIb comparison with an embedded phase I/IIa TLPO trial, while listing TLPLDC-G among adverse-event groups. In addition, the model field says SINGLE GROUP despite the randomized allocation and treatment and placebo descriptions. This makes clear reporting of trial scope, group structure, and analysis populations especially important. The registry does not resolve these issues.

In general, a time-to-event outcome can contain information about both whether and when events occur. Reporting only an incomplete set of counts or timepoints may not convey the full result. Clear estimates with uncertainty, definitions of events and censoring, and the prespecified analysis are important for interpretation. Those primary-outcome elements are not reported in the registry record.

The case also illustrates why a completed-trial label should not be mistaken for a complete statistical account. Registry transparency depends on reporting methods and results in a form that allows readers to assess the planned question, the actual analysis, and its limitations. Here, the record conveys the rationale and intended comparison, but not enough primary data to support a conclusion about the effect of the vaccine approach.

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.

Important trial-specific limitations in interpreting this registry entry arise from incomplete reporting and inconsistent descriptors. The record identifies randomized allocation and treatment and placebo arms, but its model label is SINGLE GROUP. It also includes an embedded TLPO study in the official title and additional TLPO and TLPLDC-G adverse-event groups, without fully explaining how those groups relate to the primary randomized comparison.

The primary outcome is described as DFS at 24 months and as participant counts at displayed timepoints, while the result reduction indicates several categories or time points rather than a single comparison. The record does not report the primary values, effect estimate, confidence interval, or p-value. It also does not provide the event definition, time origin, censoring method, or details needed to determine how the endpoint was analyzed.

The registry description mentions an interim analysis, but whether it occurred and how its results were handled are not reported in the registry record. The statistical analysis plan, multiplicity approach, missing-data methods, analysis populations, participant flow, and trial-specific sample-size justification are also not reported. The adverse-event term percentages lack a clearly stated denominator or group assignment in the record. These gaps limit both efficacy interpretation and comparative safety assessment.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase IIB TL + YCWP + DC in Melanoma — NCT02301611.
• Registry record last updated 2024-11-29; status last verified 2024-11.
• Results first posted 2024-11-29.
• 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

The registry record describes a completed, randomized, triple-masked phase IIb trial of an autologous TLPLDC vaccine approach versus unloaded YCWP with autologous DC control in resected stage III and stage IV melanoma. Enrollment is recorded as 187. The primary endpoint is DFS at 24 months, and the description also refers to an interim median-DFS comparison. An embedded TLPO study and additional adverse-event groups are listed, while the model label is SINGLE GROUP.

Primary DFS outcome values and inferential results are not reported in the registry record. The record also does not report the analysis plan, analysis populations, missing-data methods, or whether the interim analysis occurred. Adverse-event counts and listed serious-event terms are available, but the information is insufficient for a complete comparative safety interpretation.