A Phase II Study of High Dose Bolus IL2 in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy: Efficacy and Biomarker Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of High Dose Bolus IL2 in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy: Efficacy and Biomarker Study (NCT02796352), a na phase 2 study. The primary outcome is Response Rate.

2. Clinical Question

The clinical question is whether responses were observed after high dose bolus IL-2 in this specified population, and what side effects were recorded. The study was not designed as a randomized comparison between IL-2 and another treatment: its single-group structure means any observed outcome would describe participants receiving IL-2, not an estimated difference against a concurrent control. The registry lists progression-free survival, overall survival, and HD IL2 levels as secondary outcomes, but their results are not reported in the registry record. The enrollment recorded was 1, and the study status is terminated. Those details sharply limit how much can be learned about response frequency or variability from the record. In particular, the record does not report a primary response count or percentage. The appropriate statistical reading is therefore a description of the study question and its limits, not a conclusion about treatment effect.

3. Trial Design

This was a Phase II, single-group study of high dose bolus interleukin-2 in patients with inoperable stage III or stage IV melanoma after progression on nivolumab or pembrolizumab. The registry records no masking, allocation as not applicable, and a single-group model. There is no separate randomized or concurrent control arm in the described design.

The registry lists enrollment as 1 and the study status as terminated. The start is recorded as 2016-09, and primary completion as 2017-02-16. The planned timeframe for the primary outcome is described as up to 15 months for accrual, plus 6 months of intervention for the last subject enrolled, with 21 months stated in parentheses. These planned timeframes do not establish that the planned accrual or follow-up was completed; the record does not report the reason for termination or the participant’s follow-up duration.

The primary outcome is response rate, defined as the percentage of complete responses plus partial responses based on RECIST version 1.1. Secondary outcomes listed are progression-free survival, overall survival, and HD IL2 levels. The registry lists four outcome measures in total, but the response result and results for the secondary outcomes are not reported in the registry record. The record lists 0 analyses. It does not report the protocol-level statistical plan, eligibility details beyond the described disease and prior-treatment history, or analysis populations.

A single-group design can describe outcomes among treated participants, but it cannot directly estimate a difference from an untreated or alternative-treatment group. That distinction matters especially when interpreting a small enrollment: a recorded count of 1 is not enough to characterize variation among participants or establish a stable response rate.

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 Response Rate, measured over Up to 15 months for accrual, plus 6 months of intervention for last subject enrolled (21 months).

The primary endpoint is response rate, defined in the registry as the percentage of complete responses plus partial responses based on Response Evaluation Criteria in Solid Tumors, version 1.1. The endpoint is expressed as a percentage, while the recorded measure type is a count of participants. The registry does not report the response count, percentage, or assessment result, so no observed response rate can be stated.

In general, a response endpoint groups participants according to whether they meet specified criteria for complete or partial response at an assessment. Combining these categories gives a concise measure of tumor response, while retaining the distinction from outcomes such as progression-free survival or overall survival. Response rate does not, by itself, describe how long a response lasts or how an outcome compares with what would have happened under another treatment. Those questions require other outcome measures or an appropriate comparison design.

Response rate is commonly used in clinical studies to describe the proportion of participants meeting a defined response criterion. Its interpretation depends on the assessment rules, the participants included in the denominator, and the completeness and timing of assessments. The registry record names RECIST version 1.1 and gives an intended timeframe of up to 15 months for accrual plus 6 months of intervention for the last subject enrolled. It does not report the assessment schedule, the denominator used for analysis, or the response findings. Consequently, the endpoint definition is available, but its observed value and precision are not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available design is a single-group Phase II study, not a randomized comparison. The registry records allocation as not applicable and masking as none. In general, a single-group study can report what happened among participants who received the intervention, but it cannot isolate an intervention effect by comparing outcomes with a concurrent control group. Differences from historical experience, if considered, would require additional information and assumptions; the registry record does not report such a comparison.

The primary outcome is binary at the participant level: a participant either meets the response definition or does not. The registry defines response as complete response plus partial response under RECIST version 1.1. A response rate is generally calculated from the number meeting that definition divided by the analysis denominator. The registry record does not report either the response count or the denominator used for the primary analysis, so that rate cannot be stated. It also does not report whether all enrolled participants were considered evaluable or how unassessed participants would have been handled.

General statistical interpretation of a proportion should account for sampling uncertainty. A confidence interval is a range of values compatible with the observed data under a specified method; it communicates precision, not a guarantee that the true value lies in a particular range. With very few observations, the interval would generally be wide, and a single participant’s status could substantially affect the estimate. No confidence interval or interval method is reported in the registry record, and the absence of response data prevents an independent calculation.

The record lists enrollment of 1. That is the enrollment count, not a sample-size justification, and it should not be confused with a target needed to achieve a particular precision or power. The registry does not report a trial-specific sample-size justification. Planning illustrations based on assumed significance level, allocation, approximation, and effect size are not observations from the trial and do not establish achieved power. The listed illustration assumptions are two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. Those are planning assumptions, not evidence that this single-group study used a two-arm design or conducted the corresponding analysis. No numerical planning result is reported in the registry record.

For time-to-event outcomes such as progression-free survival and overall survival, general methods often account for different follow-up times and participants whose event status is not known at the end of observation. Such methods depend on event definitions, censoring rules, follow-up, and analysis populations. The registry lists these outcomes but does not report estimates, event definitions, censoring rules, or an analysis method. The same caution applies to the planned timeframe: a stated follow-up window is not a substitute for participant-level follow-up data.

Statistical tests and p-values are not reported in the registry record. In general, a p-value describes how inconsistent data are with a specified statistical model and null hypothesis; it is not a direct measure of effect size, clinical importance, or probability that a treatment works. A p-value would not resolve the central design limitation: there is no control group for a direct comparative estimate. Nor can a test replace a reported response count, estimate, and measure of uncertainty.

Over-dispersion is a general concern when count data vary more than a model assumes. The primary endpoint is defined as a participant response count and is ordinarily handled as a binary outcome or proportion, so a count-model dispersion assessment is not reported. The registry does not give a statistical model for any outcome. For the secondary biomarker outcome, the measurement scale, distribution, and planned analysis are not reported, so no specific model can be attributed to the study.

Finally, the registry lists 0 analyses. This means that the available record does not present analytical results for the listed outcomes. It does not supply enough information to reproduce a response estimate, quantify its precision, or assess the assumptions of an outcome model. Statistical explanations of proportions, intervals, and time-to-event methods are general concepts; they should not be mistaken for methods documented as having been used in 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("High Dose Bolus Interleukin-2 (HD IL2)")
n      <- c(1)
events <- c(0)
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  High Dose Bolus Interleukin-2 (HD IL2)  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome of response rate and three secondary outcomes: progression-free survival, overall survival, and HD IL2 levels. It also records four outcome measures in total. The registry record does not report a multiplicity strategy, such as whether outcomes were treated as separate descriptive measures or whether any adjustment was planned for multiple statistical tests. No analyses or p-values are listed, so the impact of multiplicity on reported inferences cannot be assessed.

In general, examining multiple outcomes or repeated tests can increase the chance of at least one apparently notable finding by chance. Statistical plans may address this through prespecified outcome hierarchy, adjustment methods, or a clear distinction between confirmatory and exploratory analyses. None of those details is reported in the registry record. The presence of several listed outcomes alone does not indicate that a particular adjustment was used.

Missing-data handling is also not reported in the registry record. It does not state whether the enrolled participant completed response assessment, how an unavailable assessment would be classified, or how incomplete follow-up would be handled for progression-free or overall survival. The denominator and analysis population for the primary response endpoint are not reported. No intention-to-treat, per-protocol, or evaluable-participant definition is listed.

These omissions matter because the interpretation of a response proportion depends on who is included in its denominator, while time-to-event analyses depend on follow-up and censoring conventions. The registry’s enrollment count and outcome definitions do not resolve those questions. With 0 analyses recorded and no outcome results listed, there is no basis for judging how missingness, multiplicity, or analysis-population choices affected any estimated 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 non-serious adverse event terms

The registry lists one group, High Dose Bolus Interleukin-2 (HD IL2). For serious adverse events, 1 participant was listed as at risk and 0 as affected. For other adverse events, 1 was listed at risk and 1 affected. The death count is 1. These are counts recorded for a group with enrollment of 1; they are not a basis for estimating safety frequencies in a broader population.

The registry record does not report serious adverse-event terms, and it does not provide event descriptions, dates, severity grades, duration, or a determination of whether an event was related to the intervention. It also does not state the cause or timing of the recorded death or whether it was considered treatment-related. A death recorded in the group should not be interpreted as caused by the intervention without that information.

In general, adverse-event counts describe observed events in the recorded study group, while interpretation depends on definitions, observation time, attribution, and completeness of reporting. With only one participant listed at risk, the counts are especially limited as estimates of event probability. The registry entries describe what is recorded; they do not establish a causal relationship or a stable rate of serious or other adverse events.

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

The record establishes that a Phase II study was registered to examine high dose bolus IL-2 in patients with inoperable stage III or stage IV melanoma after progression on nivolumab or pembrolizumab. It identifies response rate as the primary outcome and lists progression-free survival, overall survival, and HD IL2 levels as secondary outcomes. It also records a single-group design, termination, and enrollment of 1.

Those details do not provide an efficacy result. The response rate, response count, and secondary outcome results are not reported in the registry record. It is therefore not possible to state how many participants responded, estimate a response proportion, or describe survival outcomes from this record. Missing results should not be interpreted as no response or as evidence of a particular outcome.

The single-group design also limits what any observed outcome could establish. A description of outcomes among treated participants would not, by itself, show how those outcomes compare with an alternative treatment or with no treatment. The record does not provide a concurrent comparator or a comparative effect estimate.

Safety entries are similarly limited. The registry records 0 affected by serious adverse events among 1 at risk, 1 affected by other adverse events among 1 at risk, and 1 death. It does not report the event details or the relationship of the event or death to the intervention. These counts cannot establish causation or give a precise safety estimate.

In general, a clinical result is most informative when its estimate is paired with the number of participants assessed, a clear analysis population, and a measure of uncertainty. Those elements are not available for the primary endpoint in the registry record. The study’s enrollment and status can be described, but the record does not support a conclusion about the size or precision of a response effect, nor a comparative claim about treatment.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly stated clinical question and the very limited outcome information recorded. The registry defines a primary endpoint, response rate, and specifies that complete and partial responses are assessed using RECIST version 1.1. Yet it records enrollment of 1, termination, and 0 analyses, with no response result listed. This makes the distinction between a registered outcome and a reported outcome essential.

The single-group design is also an important feature to recognize. It can frame a descriptive question about outcomes among participants receiving high dose bolus IL-2, but it does not provide a randomized comparison. Any efficacy claim would require an appropriate comparator and a reported estimate; neither is available in the registry record. Even if a response result were present, the enrollment count would leave little information about how outcomes vary across participants.

In general, clinical researchers need to distinguish among the target population, the participants actually enrolled, and the group included in each analysis. The registry describes a population with advanced melanoma after prior anti-PD1 treatment, but it does not report an analysis population or outcome denominator. That makes it impossible to assess the representativeness of the observed participants or the precision of any estimate.

The safety entries further illustrate why counts need context. The record lists adverse-event and death counts but omits event details and attribution. Statistical summaries do not establish causation without supporting design and clinical information. In this case, the small recorded enrollment and absent outcome analyses constrain both efficacy and safety interpretation.

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 main limitation is that enrollment is recorded as 1 while the registry lists 0 analyses and does not report a response result. The primary endpoint is defined, but there is no response count, percentage, estimate of uncertainty, or analysis denominator in the registry record. The listed secondary outcomes also have no results reported. This prevents quantitative interpretation of efficacy or survival outcomes.

The study is single-group, with allocation not applicable and no masking. There is no concurrent control group in the described design, so the record cannot support a direct comparison with another treatment. The registry does not report a protocol-level statistical plan, sample-size justification, analysis populations, missing-data rules, or multiplicity approach. The reason for termination is not reported in the registry record.

Follow-up and assessment details are also limited. Although the primary outcome timeframe is stated as up to 15 months for accrual plus 6 months of intervention for the last subject enrolled, participant-level follow-up and assessment schedules are not reported. Event definitions and censoring rules for the listed survival outcomes are also not reported in the registry record.

The adverse-event entries lack descriptions, timing, severity detail, and attribution. With only 1 participant listed at risk, the counts cannot characterize the range of possible events or provide a precise estimate of risk. The death count cannot be assigned a cause or relationship to the intervention from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase II Study of High Dose Bolus IL2 in Patients With Inoperable Stage III or Stage IV Melanoma Who Have Failed Prior Anti-PD1 Immunotherapy: Efficacy and Biomarker Study — NCT02796352.
• Registry record last updated 2018-04-20; status last verified 2018-03.
• Results first posted 2018-04-20.
• 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 NCT02796352, a Phase II, single-group study of high dose bolus interleukin-2 for patients with inoperable stage III or stage IV melanoma after progression on nivolumab or pembrolizumab. It lists no masking, allocation as not applicable, enrollment of 1, and status as terminated. The start is recorded as 2016-09 and primary completion as 2017-02-16.

The primary outcome is response rate, defined as complete responses plus partial responses by RECIST version 1.1. Secondary outcomes are progression-free survival, overall survival, and HD IL2 levels. The registry lists 0 analyses; response and secondary outcome results are not reported in the registry record. Safety entries list 0 serious adverse events among 1 at risk, 1 other adverse event among 1 at risk, and 1 death. Event details, attribution, reason for termination, and the trial’s statistical plan are not reported in the registry record.