Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease. (NCT02678741), a non-randomized phase 1, phase 2 study. The primary outcome is Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Patient.

2. Clinical Question

In plain terms, the study asked whether vaccine administration alongside checkpoint-inhibitor treatment could be evaluated for safety in this patient population, and it also tracked tumor response. The clinical-course categories describe patients with no clinical response after a minimum of 3 months on checkpoint-inhibitor monotherapy, patients who developed progressive disease after an initial clinical response, and patients with stable disease for at least 6 months on monotherapy. These descriptions do not establish randomized groups, and the record does not report a direct comparison among them.

3. Trial Design

This was a multi-center Phase I/IIa study with non-randomized allocation, no masking, and a parallel model. The sponsor was Elios Therapeutics, LLC. The registry lists the study as completed, with a start date of 2016-02 and primary completion on 2019-10-30. Enrollment was 26.

The intervention was the TLPLDC vaccine added to standard-of-care checkpoint-inhibitor monotherapy for patients with metastatic melanoma and measurable disease. The registry describes patient categories according to their clinical course on checkpoint-inhibitor monotherapy: no clinical response after a minimum of 3 months, development of progressive disease following an initial clinical response, or stable disease for at least 6 months. These categories are not evidence of random assignment. The registry record does not report a randomized comparator, and the trial summary explicitly cautions that the listed groups are not a like-for-like control comparison.

The primary endpoint was a safety assessment based on graded systemic toxicities by patient over 12 months (1 year). The safety evaluation included the 16 patients who received at least one vaccine dose, rather than all 26 enrolled patients. The registry lists tumor response using RECIST criteria as a secondary outcome. It does not report detailed allocation procedures, masking procedures beyond the absence of masking, the number of participants in each clinical-course category, or a statistical analysis plan.

Because assignment was non-randomized, differences between the clinical-course categories cannot be interpreted as the effects of receiving one treatment rather than another. Patient characteristics and the reasons for belonging to a category may differ. The design can describe what was observed in the treated safety population, but the registry record does not establish a controlled estimate of the vaccine’s effect on tumor response or other clinical outcomes.

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.

Before assignment: All enrollees evaluated across all arms.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety evaluation of TLPLDC was the primary endpoint of this phase 1 trial. There were 26 patients enrolled, and 16 received at least one dose of vaccine. The population used for the safety analysis included these 16 patients. Toxicity was graded per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03. A total of 60 inoculations of TLPLDC were given to 16 patients, with the median of 3.5 inoculations.

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 Graded Standard Systemic Toxicities (Using CTCAE Graded Toxicity Scale) by Patient, measured over 12 months (1 year).

The primary endpoint was graded systemic toxicities by patient, using a CTCAE graded toxicity scale. Its stated timeframe was 12 months (1 year), and its purpose was to evaluate the safety of adding the TLPLDC vaccine to checkpoint-inhibitor monotherapy. The registry describes the endpoint as a Phase I safety evaluation. It states that 26 patients enrolled and that 16 received at least one vaccine dose; those 16 patients formed the safety-analysis population.

In general, a toxicity endpoint records whether participants experienced treatment-related or treatment-emergent problems and how those problems were graded under a defined system. Summarizing toxicity by participant helps describe how many people experienced events, rather than only counting event occurrences. Grading can also distinguish levels of severity. This is a general explanation of the endpoint type; the registry record does not report the specific grading rules, toxicity thresholds, or a full endpoint definition in the available description.

The posted adverse-event summary reports serious and other adverse-event counts, but those summaries should not automatically be treated as a complete result for the graded primary endpoint. The registry record does not report the primary endpoint’s full participant-level toxicity results, the distribution of toxicity grades, or the statistical analysis used for that endpoint. The outcome is useful for describing safety, but it does not by itself establish comparative safety when there is no randomized control group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation of this trial depends first on recognizing what its design can and cannot estimate. It was non-randomized and unmasked. In general, randomization helps balance measured and unmeasured factors between treatment groups, while masking can reduce some forms of bias in outcome assessment or reporting. Neither feature is reported as part of the design. Consequently, the study’s descriptive safety counts should not be treated as a randomized comparison, and clinical-course categories should not be read as equivalent control and intervention arms.

What does a participant-level toxicity count represent?

The primary endpoint is described as graded systemic toxicities by patient over 12 months (1 year). A participant-level count asks how many people experienced an event, rather than how many total events occurred. That distinction matters because one participant can experience more than one event. A participant-based summary can communicate the proportion of the safety population with an event, while a separate event count would describe the total burden of recorded events. The registry record does not report a complete breakdown of primary-endpoint toxicity grades or event counts, so those details cannot be reconstructed from the adverse-event summary alone.

In general, an adverse-event table should be read with attention to the group at risk, the event definition, the observation period, and whether the count refers to participants or events. Here, the summary states the numbers at risk and affected for serious and other adverse events. It also lists deaths. The record does not report the causes of death, their timing, or their relationship to study treatment. Those counts therefore describe recorded events, not attribution.

Why does the design affect interpretation?

In general, a randomized comparison is designed to make treatment groups comparable at the start, subject to chance variation. In a non-randomized study, group membership can be related to prognosis, previous response, or other clinical factors. This is particularly relevant because the registry’s clinical-course descriptions refer to response or disease status during checkpoint-inhibitor monotherapy. A comparison across those categories would mix treatment exposure with differences in clinical history. Statistical adjustment can sometimes address measured differences, but the registry record does not report an adjusted comparative analysis or the data needed to evaluate one.

The absence of masking is also relevant in general, especially for outcomes that involve clinical grading or assessment. The record does not report how toxicity grading was reviewed or whether any independent assessment process was used. That missing information does not prove that assessment was biased; it means that the record does not let readers assess the procedures.

How should uncertainty be assessed?

In general, an estimate should be interpreted alongside a measure of uncertainty. A confidence interval conveys how precisely an estimate is determined by the data and analysis assumptions. A p-value addresses compatibility with a specified null hypothesis under those assumptions; it is not a measure of clinical importance or the probability that a hypothesis is true. The registry record does not report inferential analyses, confidence intervals, or p-values for the listed outcomes. The event counts alone do not supply those missing analyses.

For binary outcomes, such as whether a participant experienced an event, uncertainty depends on both the observed count and the number of participants assessed. Small safety populations can yield imprecise estimates, even when the observed count is low. This is a general statistical point, not a new numerical estimate for this study. The study’s safety population included 16 participants, and the registry does not provide a confidence interval for the serious adverse-event count.

What do the planning illustrations mean?

The accompanying sample-size section presents planning illustrations computed from the observed effect under stated assumptions. The assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustrated effect is a stated fraction of the observed effect. Such illustrations describe hypothetical sample sizes for a future design under those assumptions. They are not the trial’s own sample-size justification, and the registry record does not report that justification. They are also not observed power: power is a design property under assumed effects, whereas a post hoc calculation based on an observed effect cannot establish how informative the completed trial was.

In general, a normal approximation can be useful for planning, but its suitability depends on the outcome, event frequency, and sample size. The registry record does not report enough methodological detail to assess the assumptions behind any particular illustration beyond those stated. The calculations should therefore be read as conditional planning examples, not as evidence that the trial was adequately powered or that a treatment effect was demonstrated.

What remains unspecified?

The record lists three outcome measures overall and identifies tumor response using RECIST criteria among secondary outcomes. When multiple outcomes are examined, multiplicity can matter: repeated testing may increase the chance of a nominally notable result arising by chance. In general, a prespecified hierarchy or adjustment can address some multiplicity concerns. The registry record does not report a multiplicity strategy, an outcome hierarchy, interim analyses, or a statistical analysis plan. It also does not report how missing outcome data were handled. Without these details, readers cannot determine whether all outcomes were analyzed as planned or how incomplete follow-up affected the results.

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("Treatment Group")
n      <- c(16)
events <- c(12)
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  Treatment Group  16  12  75.0  47.6  92.7  50.5  89.8  50.1  89.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures overall and identifies tumor response using RECIST criteria as a secondary outcome. The primary endpoint is the graded toxicity assessment. Considering more than one outcome raises a general multiplicity question: if many outcomes or comparisons are tested, the chance of at least one apparently notable result can increase. A prespecified testing sequence or adjustment may be used to address that issue. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or which analyses were designated as confirmatory.

The record lists no statistical analyses. It does not report an analysis plan, interim analyses, or procedures for handling missing outcome data. It also does not describe whether all enrolled participants were followed for the full stated timeframe or how participants with incomplete follow-up contributed to each outcome. These details matter because missing outcomes can affect both the apparent event frequency and the precision of an estimate. The safety population is explicitly described as the 16 participants who received at least one vaccine dose, whereas enrollment was 26; the registry record does not explain the inclusion of the remaining enrolled participants in relation to safety follow-up.

In general, the analysis population should match the question being asked. A treated safety population can describe events among those who received the vaccine, while an intention-to-treat population is often used for randomized treatment comparisons. This study was not randomized, and the registry does not report an intention-to-treat analysis. The available record therefore does not support assumptions about how participants were analyzed beyond the stated safety population. None of these missing details can be filled in from the posted adverse-event counts.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summary lists 16 participants at risk for serious adverse events, with 0 affected. For other adverse events, it lists 16 at risk and 12 affected. It also records 4 deaths. These are counts in the registry summary; they should be read alongside the stated group and denominator, rather than as standalone descriptions of risk.

The category labelled other adverse events is not defined in the available registry description. It should not automatically be interpreted as a specific severity level or as a complete summary of all non-serious events. The summary also does not state whether the events were considered related to the vaccine, the checkpoint inhibitor, or another cause. For the deaths, causes, timing, and treatment relationship are not reported in the registry record.

In general, an observed count of zero does not prove that an event cannot occur, and it does not establish comparative safety without an appropriate comparison group and sufficient follow-up. The serious-event count is a description of the 16-person safety group in the posted summary. It is not the full graded-toxicity result: the registry record does not report the primary endpoint’s complete grade-specific findings or a statistical analysis of those findings.

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

The posted record establishes that the study enrolled 26 patients and that 16 received at least one dose of the TLPLDC vaccine and formed the stated safety population. Its adverse-event summary reports 0 serious adverse events among 16 at risk, 12 affected in the other adverse-event category among 16 at risk, and 4 deaths. These figures describe the registry’s reported safety summary; they do not establish the causes of the events or their relationship to study treatment.

The study’s purpose included assessing safety and tumor response. The primary endpoint was graded systemic toxicity over 12 months (1 year), and tumor response using RECIST criteria was listed as a secondary outcome. However, the registry record does not report full primary-endpoint results by toxicity grade, a tumor-response estimate, or statistical analyses that quantify uncertainty. The posted counts therefore do not answer every outcome question identified by the study.

The design also limits what can be concluded about treatment effects. The study was non-randomized and unmasked, and the registry describes clinical-course categories based on response or disease status during checkpoint-inhibitor monotherapy. Those categories do not constitute a like-for-like randomized control comparison. Outcomes in this study cannot, from the available record, be separated from differences in participants’ clinical courses or other factors.

In general, an observed event count is descriptive evidence about the participants and follow-up represented in the record. It is not by itself proof of benefit, harm, or comparative effectiveness. The absence of a reported serious adverse event in this summary should not be interpreted as proof that serious events are impossible, and the reported deaths should not be attributed to treatment without information the registry does not report. The sample-size illustrations elsewhere on the page are planning examples, not observed power or proof of a treatment effect.

The appropriate reading is therefore bounded: the registry offers limited safety counts for the stated safety population and documents the study’s intended endpoints and design. It does not provide the detailed analyses needed to estimate comparative effects or judge their precision. These results should not be generalized beyond the population and information represented in the record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between a safety description and a comparative treatment-effect estimate. The registry reports participant counts and adverse-event categories, but the study was non-randomized and the described clinical-course groups are not like-for-like controls. That distinction is essential: a set of observed outcomes can describe what was recorded without identifying what would have happened to comparable patients under a different treatment strategy.

The separation between enrollment and the safety population is also important. The record reports 26 enrolled patients and 16 who received at least one vaccine dose and entered the safety analysis. Readers need to know which population forms each denominator; using the enrollment count as the denominator for the safety summary would misrepresent the posted analysis group. The record does not explain the reasons for the difference or provide a complete account of follow-up for those not included in the safety population.

The endpoint highlights another useful statistical principle. Graded toxicity by participant is not interchangeable with a count of all adverse events, and a summary of serious and other events does not necessarily give the full primary-endpoint result. Clear definitions, participant-level reporting, severity grades, and follow-up information are needed to understand a safety endpoint fully. Several of those details are not reported in the registry record.

Finally, the planning illustrations should be kept separate from the evidence generated by the trial. They show how sample-size planning depends on assumptions, but they are not a substitute for randomization, complete outcome reporting, or an analysis plan. The page is useful for reading both the available counts and the limits of what can be inferred from them.

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 registry record leaves important trial details unspecified. It does not report the statistical analysis plan, the rationale for the enrollment target, interim analyses, or the handling of missing outcome data. It also does not describe the reasons that 16 of the 26 enrolled participants formed the stated safety population. These omissions make it difficult to assess how completely the posted summaries represent the enrolled population.

The primary endpoint was graded systemic toxicity by patient over 12 months (1 year), but full results by toxicity grade and a complete endpoint analysis are not reported in the registry record. The adverse-event summary gives counts for serious and other adverse events and lists deaths, but it does not report event causes, timing, or treatment attribution. The other adverse-event category is not defined in the available description.

The study was non-randomized and unmasked. Its clinical-course descriptions refer to response or disease status during checkpoint-inhibitor monotherapy, so the groups cannot be assumed to be comparable. The registry record does not report a concurrent randomized control group or an adjusted comparative analysis. As a result, comparisons across those categories would be vulnerable to differences in clinical history and other factors.

The record lists RECIST tumor response as a secondary outcome, but response results and their uncertainty are not reported. The registry also does not report a multiplicity strategy, outcome hierarchy, or confidence intervals. The planning illustrations use stated assumptions, but the record does not report a trial-specific sample-size justification. These limitations constrain conclusions about treatment effects and precision, beyond the descriptive safety counts that are posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Multi-center Phase I/IIa Trial of an Autologous Tumor Lysate (TL) + Yeast Cell Wall Particles (YCWP) + Dendritic Cells (DC) Vaccine in Addition to Standard of Care Checkpoint Inhibitor of Choice in Metastatic Melanoma Patients With Measurable Disease. — NCT02678741.
• Registry record last updated 2024-03-12; status last verified 2024-03.
• Results first posted 2024-03-12.
• 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

This completed, multi-center Phase I/IIa study evaluated a TLPLDC vaccine added to standard-of-care checkpoint-inhibitor monotherapy in patients with stage IV metastatic melanoma and measurable disease. It was non-randomized, unmasked, and parallel. The registry reports 26 enrolled patients and a safety population of 16 participants who received at least one vaccine dose.

The primary endpoint was graded systemic toxicity by patient over 12 months (1 year). Tumor response using RECIST criteria was listed as a secondary outcome. The adverse-event summary reports 0 serious adverse events among 16 at risk, 12 affected in the other adverse-event category among 16 at risk, and 4 deaths. The registry record does not report full primary-endpoint results, tumor-response results, or inferential analyses. The design does not provide a randomized, like-for-like control comparison.