Immunotherapy Study for Patients With Stage IV Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Immunotherapy Study for Patients With Stage IV Melanoma (NCT02054520), a randomized phase 2 study. The primary outcome is Safety and Tolerability Assessed by Development of AEs and Laboratory Parameters.

2. Clinical Question

The trial was designed around a clinical question about adding an experimental immunotherapy to checkpoint inhibition for stage IV melanoma. Its registry summary also describes hypotheses involving tumor stabilization or shrinkage and longer progression-free, disease-free, or overall survival. Those statements describe the study rationale, not findings. The available primary outcome concerns safety and tolerability, and the posted numerical information consists of adverse-event counts by arm. It does not establish whether any regimen changed survival, tumor response, or other clinical outcomes.

3. Trial Design

This was a phase 2, randomized, parallel-group study with no masking reported. The registry record gives enrollment as 47 and lists the study status as terminated. The study start is recorded as 2014-06, and primary completion as 2018-04-05. A reason for termination is not reported in the registry record.

The arms paired each of three checkpoint inhibitors—ipilimumab, nivolumab, and pembrolizumab—with either HAM immunotherapy or checkpoint-inhibitor treatment alone. The descriptions specify ipilimumab at 3 mg/kg every 3 weeks for four doses in the monotherapy arm, and pembrolizumab at 2 mg/kg every 3 weeks in its monotherapy arm. The nivolumab-alone description specifies 3 mg/kg every 2 weeks. Combination-arm descriptions include HAM immunizations of 300 Million cells per immunization, with schedules extending from weekly dosing to less frequent dosing over time. The HAM-plus-nivolumab description also states nivolumab dosing every 2 weeks.

The registry record identifies randomization but does not report the allocation ratio, sequence-generation method, concealment procedures, or whether randomization was stratified. Masking is listed as none, so the study is described as open-label. Specific details about treatment adherence, discontinuation rules, and handling of treatment changes are not reported in the registry record. These design details matter when interpreting arm-level safety counts, because open-label treatment and different treatment schedules can affect how events are observed, recorded, and compared.

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: The enrollment and treatment phase of this trial was terminated early, but the FDA required 15 year long term follow-up for gene therapy is still ongoing.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary population for safety analyses is the safety analysis set, defined as all randomized subjects who receive at least one administration of study treatment (dorgenmeltucel-L or immune checkpoint therapy).

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety and Tolerability Assessed by Development of AEs and Laboratory Parameters, measured over 2 years.

The primary outcome is titled Safety and Tolerability Assessed by Development of AEs and Laboratory Parameters. It is defined as the number of participants with an event, with a timeframe of 2 years. The stated purpose is to assess safety for checkpoint inhibition with or without dorgenmeltucel-L in people with stage IV melanoma. The primary safety population includes randomized participants who received at least one administration of study treatment.

Safety endpoints are used to describe the occurrence of unwanted medical events and laboratory changes during treatment and follow-up. Counting participants with events gives a straightforward description of how many people in each arm were recorded as affected. It does not, by itself, describe the number of separate episodes, their duration, severity, timing, or relationship to treatment. Laboratory parameters may also require defined thresholds and timing rules for interpretation; those details are not reported in the registry record.

The primary outcome title covers adverse events and laboratory parameters, but the posted outcome information does not give a single category-by-category result or a single comparison between regimens. The registry record notes that the primary outcome has several categories or time points and is not reduced to one comparison. Thus, the available event counts should be read as descriptive safety information rather than as a complete summary of every endpoint component.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, parallel-group phase 2 study with no masking. Randomization is intended, in general, to reduce systematic differences between treatment groups at assignment. It does not guarantee that small groups will be alike in every characteristic, and it does not remove uncertainty from estimates. The registry record does not report the randomization procedure or allocation ratio, so those features cannot be assessed from the posted information.

What does a participant count measure?

The primary outcome is expressed as the number of participants with an event. In general, such a count records whether each person met an event definition during the stated observation period. It is different from counting every event episode: one participant can have more than one event, but a participant-based count typically identifies that person as affected. The registry record does not specify event-level counting details, severity thresholds, or the criteria used for laboratory abnormalities.

Counts need their corresponding denominators for context. The serious-event entries include both participants at risk and participants affected, which permits the reported arm-level counts to be read in that context. However, the arm groups are small and unequal in size. A count in one arm should not be compared with another as though the denominators and precision were identical. No calculated relative effects or confidence intervals are posted.

Why does uncertainty matter?

As a general statistical point, a confidence interval describes a range of values compatible with the observed data under a specified statistical model. Wider intervals indicate less precision. In small groups, even a difference in observed counts can be compatible with a broad range of underlying event frequencies. No confidence intervals are reported for these safety counts, so the precision of any between-arm contrast is not quantified in the registry record.

As a general point, a hypothesis test asks whether the data are inconsistent with a specified null hypothesis under its assumptions. A p-value does not measure the probability that a treatment is effective or safe. Here, the registry record lists no posted analyses, p-values, or formal hypothesis tests. There is therefore no basis in the posted results for describing a statistically significant or nonsignificant difference between any treatment arms.

How should the sample-size illustration be read?

The sample-size material is described as a planning illustration based on the observed effect, not as the trial’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. In general, a planning calculation estimates the number of participants that might be needed under specified assumptions; it is not an observed trial outcome and it is not observed power. The registry record does not report the trial’s own sample-size justification. No particular planning sample-size values are reported in the record information.

More generally, planning calculations based on an observed effect can be unstable when the original groups are small: the observed effect may be imprecise, and the assumptions may not match a future study. Such calculations should be treated as illustrations rather than evidence that the current study was adequately powered. The record does not provide a planned effect size or a prespecified power target for the original trial.

What analyses are available?

The registry record lists two outcome measures and zero analyses. The primary outcome spans several categories or time points and is not reduced to one comparison. No statistical model, multiplicity adjustment, interim analysis, covariate adjustment, or missing-data method is reported in the registry record. These omissions mean that the posted counts can be described, but the analysis choices underlying any broader comparison cannot be reconstructed.

10. Multiplicity, Missing Data and Analysis Populations

The primary safety outcome encompasses adverse events and laboratory parameters, and the registry record indicates that it has several categories or time points rather than one reduced comparison. In general, examining multiple outcomes or time points creates multiple opportunities for an apparently unusual result. A prespecified statistical plan can define which comparisons are primary and whether adjustments are used. The registry record does not report such a plan, any multiplicity adjustment, or any interim analyses.

The record describes the primary safety population as randomized participants who received at least one administration of study treatment. This is a treated safety population, rather than a population defined simply by randomization. In general, excluding randomized participants who did not receive treatment can affect comparability between arms if the reasons for non-treatment differ. The registry record does not report how many randomized participants, if any, received no treatment or how they were handled in analyses.

Missing-data procedures are not reported in the registry record. It does not specify how missing laboratory assessments, incomplete adverse-event follow-up, withdrawals, or incomplete outcome records were handled. The record also does not describe imputation, censoring rules, or sensitivity analyses. These details matter because a participant with incomplete follow-up may have fewer opportunities for an event to be observed.

Because the registry lists zero analyses, there are no posted inferential results with which to evaluate the effects of multiplicity or missingness. The available safety counts are descriptive. They do not establish that every randomized participant was followed for the full 2 years or that all relevant events were captured consistently.

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: gallbladder pain (33.3%), sepsis (33.3%), vomiting (16.7%), diabetic ketoacidosis (16.7%), respiratory failure (16.7%).

The serious adverse-event figures give the number of participants affected alongside the number at risk in each arm. For example, the registry reports 3 affected among 11 at risk for HAM plus ipilimumab, and 3 among 16 at risk for ipilimumab alone. Corresponding counts are 1 among 6 for HAM plus nivolumab, 2 among 6 for nivolumab alone, 0 among 5 for HAM plus pembrolizumab, and 2 among 3 for pembrolizumab alone. These are participant counts, not counts of all serious-event episodes.

The arms have different denominators, and some groups are small. A raw count alone does not express the precision of an event frequency or establish a difference between regimens. The registry does not report confidence intervals or formal comparisons for these figures. It also does not provide enough detail to determine how long each participant was observed or whether observation time was comparable across arms.

Deaths are listed separately by arm, but the registry record does not state that they were treatment-related. The serious-event term percentages are listed without an explained denominator or arm assignment. Therefore, they should be read only as the terms and percentages recorded, not as comparative treatment risks. These safety data describe reported events; they do not establish causation.

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

The posted results show that adverse events and deaths were recorded across the treatment arms, with arm-level counts varying. The registry reports serious adverse events and other adverse events as counts of affected participants, and it lists several serious-event terms with percentages. These observations describe what was recorded in this study; they do not, on their own, show that HAM changed the frequency of adverse events compared with checkpoint-inhibitor treatment alone.

Several features limit comparative interpretation. The arm sizes differ, and the record does not provide formal statistical analyses, estimates of uncertainty, or adjusted comparisons. The posted safety population is defined by receipt of at least one study treatment, and the registry does not describe missing-data handling or duration of follow-up by arm. Those factors affect how directly the counts can be compared. The event percentages also lack an explained denominator in the registry record.

The registry summary describes hypotheses about tumor stabilization or shrinkage and survival outcomes, but the primary endpoint presented is safety and tolerability. No numerical efficacy results or inferential analyses are reported in the registry record. It is therefore not possible to draw conclusions from these safety counts about tumor response, progression-free survival, disease-free survival, or overall survival.

The study status is terminated, but the reason is not reported in the registry record. Termination alone does not identify whether the cause was safety, feasibility, funding, recruitment, or another consideration. Likewise, the registry data do not establish that a particular regimen is safe or unsafe for an individual. They are a limited descriptive account of events recorded in this trial, not a complete basis for clinical decisions.

13. Why This Trial Matters Statistically

This study is statistically notable because it places three checkpoint inhibitors in a parallel randomized design, each with a corresponding regimen that adds HAM immunotherapy. That structure raises a clear comparative question: whether adding the experimental immunotherapy changes safety outcomes within each checkpoint-inhibitor regimen. The posted record, however, does not contain formal analyses answering that question.

The arm-level counts illustrate why denominator and precision matter. The serious-event counts are accompanied by the number at risk, but group sizes are small and differ. In general, estimates from small groups tend to be uncertain, and observed count differences can be strongly affected by chance. Without confidence intervals or a prespecified comparative analysis, the counts should not be read as reliable evidence of a difference between regimens.

The study also highlights the distinction between a trial’s stated rationale and its reported endpoints. The registry summary refers to tumor and survival hypotheses, whereas the primary outcome is safety and tolerability. The available numerical results do not provide an efficacy assessment. This distinction helps prevent interpretation of a study’s objectives as if they were observed findings.

Finally, the registry’s limited reporting of analyses, missing-data methods, and multiplicity procedures constrains reproducibility and interpretation. Those details are important when a primary outcome contains multiple categories or time points. The record supports a description of the posted safety counts, but not a broader claim about comparative effects or treatment benefit.

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 main limitation is that the registry record contains descriptive adverse-event counts but no posted statistical analyses. There are no reported confidence intervals, p-values, adjusted comparisons, or model-based estimates. The arm-level counts therefore do not quantify the uncertainty around comparisons between regimens.

The study enrolled 47 participants across treatment arms of different sizes. Some arm denominators are small, limiting the precision with which event frequencies can be estimated. The registry record does not report the allocation ratio or detailed randomization procedures, so the distribution of participants between arms cannot be assessed beyond the listed counts.

The primary outcome includes adverse events and laboratory parameters, but the registry record does not give all category definitions, thresholds, or assessment details. It states a 2-year timeframe but does not provide arm-specific follow-up duration or explain the handling of incomplete follow-up. Missing-data methods, treatment discontinuation rules, and sensitivity analyses are not reported.

The record also does not report the original sample-size justification, a prespecified statistical analysis plan, multiplicity procedures, or interim analyses. Its sample-size material is described as an illustration based on observed effects, rather than as the original design basis. The listed serious-event percentages have no explained denominator or arm assignment. Finally, the reason for termination is not reported, and the posted safety counts cannot address the study’s stated tumor-response or survival hypotheses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Immunotherapy Study for Patients With Stage IV Melanoma — NCT02054520.
• Registry record last updated 2023-04-18; status last verified 2023-03.
• Results first posted 2020-04-29.
• 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

NCT02054520 is a randomized, open-label, parallel-group phase 2 study in stage IV melanoma. The registry lists enrollment as 47, status as terminated, study start as 2014-06, and primary completion as 2018-04-05. A reason for termination is not reported in the registry record.

The study compared HAM immunotherapy combined with ipilimumab, nivolumab, or pembrolizumab against the corresponding checkpoint inhibitor alone. The primary outcome assessed safety and tolerability through adverse events and laboratory parameters over 2 years. The primary safety population was defined as randomized participants who received at least one administration of study treatment.

The posted record includes arm-level adverse-event counts and selected serious-event terms, but lists no statistical analyses. It does not provide formal comparative estimates, uncertainty intervals, or numerical efficacy results. The available information supports descriptive reading of the recorded safety counts, not conclusions about treatment effects on safety or efficacy.