This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Anti-PD-1 Antibody With HD IL-2 in Metastatic Melanoma (NCT03476174), a na phase 2 study. The primary outcome is Response Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03476174 |
| Phase | Phase 2 |
| Condition | Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Ralph Hauke |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with stage IV malignant melanoma. The registry record reports enrollment of 1 participant. It does not report further participant characteristics in the primary-outcome description.
Intervention
The intervention was sequential pembrolizumab followed by high-dose interleukin-2 (HD IL-2). The registry describes pembrolizumab administration followed by two cycles of HD IL-2.
Comparator
This was a single-group study, with no separate comparator group described. The registry lists allocation as not applicable and masking as none, so it does not describe a randomized, blinded comparison.
Primary question
The primary objective was to assess the response rate, defined as complete response plus partial response, for the sequential therapy. Response assessment was to use revised RECIST 1.1, with a primary-outcome timeframe of 12 months.
In statistical terms, the objective asks how many participants in the treated group met the response definition during the specified assessment period. A response rate is a proportion: the numerator is the number meeting the criterion, and the denominator is the number evaluated under the stated outcome rules. The record does not provide an analyzed numerator, denominator, or aggregate response-rate estimate.
The primary-outcome note says the funder terminated the study early and that this objective was not formally analyzed; individual subject responses are reported. The individual response values are not stated in the registry record. Consequently, the clinical question is clear, but the posted primary outcome does not quantify the response result or its uncertainty.
3. Trial Design
The registry identifies NCT03476174 as a phase 2, single-group study of pembrolizumab followed by HD IL-2 in metastatic melanoma. The study is titled “Anti-PD-1 Antibody With HD IL-2 in Metastatic Melanoma,” and its official title describes it as a pilot study evaluating activity of the combination. The listed sponsor is Ralph Hauke.
The registry records a study start date of 2018-05-07 and a primary completion date of 2019-10-16. Its status is terminated. The enrollment entry is 1. The record does not describe a concurrent control arm: allocation is listed as not applicable, and masking is listed as none. Thus, the design does not support a direct randomized comparison between treatment groups.
The intervention description specifies pembrolizumab 200 mg intravenously over 30 minutes on Day 1 of each cycle, with each cycle lasting 3 weeks (21 days), for 2 cycles. It then describes IL-2 600,000 IU/kg2 intravenously over 15 minutes every 8 hours for up to 14 doses over 5 days. Days 1-5 are identified as Cycle 1, followed by 9 days of rest, with Days 15-19 identified as Cycle 2.
The registry lists adverse events, progression-free survival (PFS), and overall survival (OS) as secondary outcomes. It does not report a statistical analysis plan, the reason for termination beyond the primary-outcome note that the funder terminated the study early, or a detailed account of the analysis population.
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
| Stage | Pembrolizumab and HD Interleukin 2 |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Due to the early termination of the study by the funder, data for this objective was not formally analyzed. Individual subject responses are reported.
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.
Population: One subject was registered to this study before termination by the funder
| Characteristic | Unit | Pembrolizumab and HD Interleukin 2 |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 1 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age, Continuous | years | 53 (53 to 53) |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 1 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 1 |
| ECOG Performance Status: ECOG PS =0 | Participants | 1 |
| ECOG Performance Status: ECOG PS =1 | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Response Rate, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is response rate, expressed as the count of participants meeting the response definition. The registry defines the objective as complete response (CR) plus partial response (PR), assessed using revised RECIST 1.1. The stated timeframe is 12 months. The description refers to assessment after pembrolizumab and reassessment after HD IL-2, consistent with the sequential intervention.
As a general statistical concept, a response endpoint converts participant-level assessments into a categorical outcome: each evaluated participant either meets the response definition or does not. The response rate summarizes the proportion who meet that definition among the participants included in the analysis. The criteria and timing matter because changes in either can alter which outcomes count as responses.
Response rate is used to describe observed antitumor activity in a defined study population and assessment window. In a single-group study, it is a description of outcomes among treated participants; without a concurrent comparator, it does not by itself estimate a treatment effect relative to another therapy or to no treatment.
The registry says the primary objective was not formally analyzed because the funder terminated the study early. Individual subject responses are reported, but the aggregate response count and response rate are not reported in the registry record. The endpoint definition is therefore available, but a formal estimate of the primary outcome is not.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main interpretive fact is that the registry record does not present a formal analysis of the primary response-rate objective. It states that the funder terminated the study early and that individual subject responses are reported. It does not give an aggregate response rate, an uncertainty interval, or a statistical test for that objective. The endpoint definition and assessment method are described, but the posted primary-outcome information does not establish the magnitude or precision of the response result.
The study was single-group and reports enrollment of 1 participant. A single-group result, even when fully analyzed, would describe outcomes among treated participants rather than provide a randomized comparison. Differences from outcomes in another population or study could reflect differences in participants, assessment, follow-up, or other factors; the registry record does not provide a control group to separate those explanations.
For a binary endpoint such as response, the estimate depends on both the number meeting the response criteria and the number included in the analysis. Those aggregate quantities are not reported for the primary objective. Without them, a reader cannot verify the response-rate estimate or judge its precision from the registry record. Nor does the record report a confidence interval or p-value for the primary endpoint.
The record lists secondary outcomes of adverse events, PFS, and OS, but the available outcome details do not include formal analyses for those endpoints. The registry lists zero analyses. This does not provide a basis for drawing conclusions about efficacy or comparative safety. The adverse-event entries should be read as descriptive registry counts and percentages in a very small reported group, rather than as precise estimates of event frequency in a broader population.
Any sample-size calculations presented as planning illustrations are not observations from this trial and are not evidence of the study’s power. The stated illustration assumptions are two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a fraction of the observed effect. These are planning conventions, not a description of this single-group study’s actual design. The registry record does not report the trial’s own sample-size justification or a formal analysis plan.
Overall, the posted record documents the study design, intervention, endpoint definition, early termination, and selected safety counts. It does not provide a formally analyzed primary response estimate. Interpretation should therefore remain limited to what the record documents rather than extending to claims about treatment effect or expected outcomes beyond this study.
9. Statistical Methods Explained
What does a response-rate endpoint represent?
General statistical explanation: A response-rate endpoint is binary at the participant level. Each participant is classified according to whether the prespecified response criteria are met. The rate is the proportion of evaluated participants classified as responders. The definition of response, assessment procedure, and observation window are part of the endpoint; changing any of them can change the result.
In this study, the registry defines response as complete response plus partial response and names revised RECIST 1.1 as the assessment framework. The primary-outcome timeframe is 12 months. The objective concerns sequential pembrolizumab followed by HD IL-2, with assessment after pembrolizumab and reassessment after HD IL-2 described in the registry. The record states that the primary objective was not formally analyzed.
Why does the denominator matter?
General statistical explanation: A proportion must be interpreted alongside the population used to calculate it. The denominator may depend on eligibility, treatment received, outcome assessment, and how missing assessments are handled. If participants are excluded from an analysis, the resulting proportion can differ from a proportion calculated among all enrolled participants. A clear report therefore identifies the analysis population and the number of participants with an evaluable outcome.
The registry record reports enrollment of 1 participant but does not state an analyzed denominator for the primary endpoint. It says individual subject responses are reported, while also stating that the primary objective was not formally analyzed. The aggregate numerator and denominator for a response-rate calculation are not reported in the registry record.
How should uncertainty be understood?
General statistical explanation: A point estimate describes the observed data, while a confidence interval communicates the range of values compatible with the data under a statistical model and its assumptions. Estimates based on very limited information are typically imprecise. A confidence interval does not remove the limitations of the study design, and it cannot turn a single-group observation into a randomized treatment comparison.
The registry does not report a confidence interval, standard error, or p-value for the primary endpoint. Since no aggregate response estimate is reported, its precision cannot be assessed from the primary-outcome information in the record. Any uncertainty calculation would also depend on an explicitly stated response count and analysis denominator, neither of which is given as an aggregate primary result.
What does the single-group design allow?
General statistical explanation: A single-group study can describe outcomes observed in the group receiving the intervention. A concurrent comparator can help distinguish an intervention-associated difference from differences that might arise from participant characteristics, time, assessment, or other influences. Without such a group, a response rate is not a comparative effect estimate.
The registry identifies the model as single-group, allocation as not applicable, and masking as none. It does not describe a control group. The design therefore does not provide a randomized comparison, and the posted record does not report an adjusted or unadjusted comparison between arms.
Are the planning assumptions the trial’s analysis plan?
General statistical explanation: Sample-size planning calculations estimate how many observations might be needed under specified assumptions. Their results depend on the chosen effect size, significance level, allocation, statistical model, and desired power. A planning illustration is not an observed outcome and does not establish the power achieved by a completed study.
The registry’s sample-size assumptions describe a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The illustration defines the effect to detect as a stated fraction of the observed effect. The record does not report that these assumptions were the trial’s own design plan. They do not match the reported single-group structure as a description of the actual comparison, and no resulting sample-size figures are stated in the registry record.
What can be inferred from the listed analyses?
General statistical explanation: A statistical analysis normally specifies the endpoint definition, analysis population, handling of missing observations, model or summary measure, and how uncertainty is quantified. A registry entry may describe an outcome without reporting a completed analysis. An outcome definition alone is not a result.
The registry lists zero analyses. It also states that the primary objective was not formally analyzed following early termination by the funder. The analysis population, missing-data method, and inferential procedure for the primary outcome are not reported in the registry record. Consequently, no formal estimate or inferential conclusion for the primary response endpoint can be reconstructed from the record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary objective, response rate, and secondary outcomes of adverse events, PFS, and OS. It does not report a multiplicity strategy for interpreting several outcomes. In general, when multiple outcomes are tested, the chance of at least one apparently notable result can increase; a prespecified approach may address that issue. No such approach is reported in the registry record, and the primary endpoint was not formally analyzed.
The record states that the funder terminated the study early and that individual subject responses are reported. It does not describe how missing response assessments were handled, whether all enrolled participants were included in the primary analysis, or how the analysis population was defined. These details are important because the denominator and treatment of unavailable assessments can affect a response-rate estimate.
The registry lists zero analyses. It does not report the statistical methods used for PFS or OS, follow-up rules, censoring procedures, or analysis populations for those outcomes. Their inclusion as secondary outcomes is not, by itself, evidence that a formal analysis was completed.
As a general principle, missing-data methods and multiplicity procedures should be specified before examining outcome results where possible, because different choices can affect interpretation. For this study, those methods are not reported in the registry record. The early termination and lack of a formal primary analysis further limit what can be concluded from the posted outcome information.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pembrolizumab and HD Interleukin 2 | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pembrolizumab and HD Interleukin 2 | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pembrolizumab and HD Interleukin 2 | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Pembrolizumab and HD Interleukin 2 |
|---|---|---|
| ENCEPHALOPATHY GR 4 | Nervous system disorders | 1 of 1 |
| HEPATIC FAILURE GR 4 | Hepatobiliary disorders | 1 of 1 |
| HYPOXIA GR 4 | Respiratory, thoracic and mediastinal disorders | 1 of 1 |
| RESPIRATORY FAILURE GR 4 | Respiratory, thoracic and mediastinal disorders | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pembrolizumab and HD Interleukin 2 |
|---|---|---|
| CREATININE INCREASED GR 3 | Investigations | 1 of 1 |
| HYPOTENSION GR 3 | Cardiac disorders | 1 of 1 |
| ALLERGIC REACTION GR 2 | Immune system disorders | 1 of 1 |
| DIARRHEA GR 2 | Gastrointestinal disorders | 1 of 1 |
| DIZZINESS GR 2 | Nervous system disorders | 1 of 1 |
| HOARSENESS GR 2 | Respiratory, thoracic and mediastinal disorders | 1 of 1 |
| TREMOR GR 2 | Nervous system disorders | 1 of 1 |
| WEIGHT LOSS GR 2 | Investigations | 1 of 1 |
| EDEMA LIMBS GR 1 | General disorders | 1 of 1 |
| EDEMA TRUNK GR 1 | General disorders | 1 of 1 |
Serious events with the highest arm-level rate: encephalopathy gr 4 (100.0%), hepatic failure gr 4 (100.0%), hypoxia gr 4 (100.0%), respiratory failure gr 4 (100.0%).
The registry reports one group titled “Pembrolizumab and HD Interleukin 2.” In that group, the entries show 1 participant at risk and 1 affected for serious adverse events, and 1 at risk and 1 affected for other adverse events. Deaths are reported as 0. The record also lists encephalopathy grade 4, hepatic failure grade 4, hypoxia grade 4, and respiratory failure grade 4, each with a reported percentage of 100.0% among the top serious terms.
These are descriptive registry figures, not comparative estimates. The reported group is very small, so the percentages should not be treated as precise estimates of event frequency in a broader population. The registry excerpt does not provide further denominator detail for each listed term or explain whether the events occurred in the same participant. It also does not provide a comparator group for assessing relative safety.
Serious adverse-event entries and other adverse-event entries are distinct registry categories; they should not be added together or interpreted as separate people without further detail. The listed terms and grades describe reported events, but they do not establish causation. The record does not provide enough information to estimate comparative risk or characterize event frequency beyond the reported counts and percentages.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase 2, single-group study evaluated sequential pembrolizumab and HD IL-2 in metastatic melanoma, and that its primary objective concerned response defined as complete response plus partial response under revised RECIST 1.1. It also establishes that the funder terminated the study early and that the primary objective was not formally analyzed.
What the record does not establish is an aggregate response rate, the precision of such an estimate, or a comparative treatment effect. Individual subject responses are described as reported, but the aggregate response result is not reported in the registry record. The posted information therefore cannot support a numerical summary of primary response or a conclusion about how the intervention compares with another treatment.
More generally, a single-group study describes outcomes among the participants who received the intervention. Without a concurrent comparator, an observed outcome cannot isolate the effect of treatment from other explanations. A small enrollment also leaves limited information for estimating how outcomes might vary across a wider population. These are design and precision limitations, not proof that an intervention does or does not have an effect.
The safety entries document reported serious and other adverse-event counts, along with listed serious terms and percentages. They should be read as descriptive observations in the registry record, not as stable population rates or causal estimates. The registry’s zero analyses and lack of a formal primary analysis mean that the statistical evidence available in the record is limited. The appropriate conclusion is about what was documented, not a clinical recommendation or a claim of benefit or lack of benefit.
13. Why This Trial Matters Statistically
This record illustrates the difference between an endpoint being defined and an endpoint being formally analyzed. The primary question is specified in clinically interpretable terms: response, defined as complete response plus partial response under revised RECIST 1.1. Yet the registry states that early termination by the funder meant the primary objective was not formally analyzed. A clear endpoint definition cannot substitute for a reported estimate.
It also highlights the interpretive limits of a single-group design. A response proportion, if reported, would summarize outcomes in the treated group. It would not by itself answer whether outcomes differ from those under another intervention. That distinction matters when readers encounter a study described as evaluating treatment activity: descriptive activity and comparative efficacy are different statistical questions.
The enrollment entry of 1 and the absence of a formal response analysis make precision especially important. A result based on very limited information would not be expected to characterize a broad population reliably. The registry does not provide an aggregate estimate or uncertainty interval to assess, so readers should not infer precision from the fact that individual responses are reported.
Finally, the record lists serious adverse events and other outcomes without a formal analysis plan or detailed account of analysis populations and missing-data handling. This makes the study a useful example of why registry status, endpoint definitions, denominators, uncertainty, and analysis methods all matter. Transparent reporting of these elements helps separate documented observations from conclusions that the design and data cannot support.
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 most direct limitation is the early termination recorded by the registry. The primary-outcome note says the funder terminated the study early and that the response-rate objective was not formally analyzed. Individual subject responses are reported, but the registry record does not give an aggregate response estimate, confidence interval, or statistical test for the primary endpoint.
The study is identified as single-group, with no comparator described, and masking is listed as none. The design therefore cannot provide a randomized comparison. Enrollment is reported as 1, which sharply limits the information available for estimating outcome frequency or variability. The registry record does not report a sample-size justification for the study itself.
The primary endpoint has a stated timeframe of 12 months and uses revised RECIST 1.1, but the record does not report the analyzed denominator or how missing response assessments were handled. It also does not report the analysis population, multiplicity approach, or detailed statistical methods for the primary endpoint. Although PFS and OS are listed as secondary outcomes, their analysis methods and results are not described in the available outcome information.
The safety information is also limited. Counts and percentages are reported for a very small group, and the record does not provide further event-level context or a comparator. These limitations mean the posted information supports a description of the trial and its reported entries, but not a precise or comparative estimate of treatment outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Anti-PD-1 Antibody With HD IL-2 in Metastatic Melanoma — NCT03476174.
- Registry record last updated 2024-10-02; status last verified 2024-09.
- Results first posted 2024-10-02.
- 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.
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18. Record Summary
NCT03476174 is a terminated phase 2, single-group study of sequential pembrolizumab followed by HD IL-2 in metastatic melanoma. The registry reports enrollment of 1 participant, no masking, and no separate comparator group. The primary objective was response rate, defined as complete response plus partial response using revised RECIST 1.1, with a 12-month timeframe.
The registry states that the funder terminated the study early and that the primary objective was not formally analyzed; individual subject responses are reported. An aggregate response rate and its uncertainty are not reported in the registry record. Secondary outcomes listed are adverse events, PFS, and OS, and the registry lists zero analyses.
The safety entries report serious and other adverse-event counts, zero deaths, and four listed grade 4 serious-event terms, each with a reported percentage of 100.0%. Given the single-group design and limited enrollment, these entries are descriptive and do not provide comparative estimates.