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 Vemurafenib and TIL Therapy for Metastatic Melanoma (NCT02354690), a na phase 1, phase 2 study. The primary outcome is Number of Reported Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02354690 |
| Phase | Phase 1, Phase 2 |
| Condition | Metastatic Melanoma |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 13 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Inge Marie Svane |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with BRAF-mutated metastatic melanoma. The registry record lists metastatic melanoma as the condition and an enrollment of 13. It does not report the characteristics of enrolled participants or the criteria used to determine which patients could take part.
Intervention
The treatment approach combined vemurafenib with adoptive cell therapy using tumor-infiltrating lymphocytes (TILs). The arm description says that patients began vemurafenib before tumor harvest, then received lymphodepleting chemotherapy, TIL infusion, and interleukin-2. The registry record describes the study as phase 1 and phase 2.
Comparator
There was no randomized or concurrent control group in the registry design: the allocation is listed as not applicable and the model as single-group. The study therefore does not provide a like-for-like comparison with another treatment or with a group receiving no study treatment.
Primary question
The primary outcome was the number of reported treatment-related adverse events. The stated purpose was to assess safety of the combination, including vemurafenib, lymphodepleting chemotherapy, TIL therapy, and interleukin-2. The registry also lists treatment-related immune responses, objective response rate, overall survival, and progression-free survival as secondary outcomes, but does not report their results.
The clinical question is therefore primarily about whether adverse events were reported during the treatment course, not whether the combination outperformed another approach. The study description also identifies feasibility, immune responses, and clinical efficacy as objectives. Those aims provide context for the intervention, but the registry record does not contain results that answer the efficacy questions. The available adverse-event figures describe events in the treated group; without a comparator, they cannot isolate the contribution of any individual component or establish how the event burden compares with another treatment strategy.
3. Trial Design
The registry describes a completed phase 1 and phase 2, single-group study of vemurafenib with TIL therapy in metastatic melanoma. Allocation is listed as not applicable, and masking as none. Enrollment is listed as 13. Because there is no concurrent comparison group, the study is not a randomized treatment comparison; its results should be read as observations in the treated group rather than as estimates of a treatment difference.
The arm description says that patients began vemurafenib before tumor harvest. They then stopped vemurafenib for admission and lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by TIL infusion and interleukin-2. The brief description says that TILs were produced from a patient’s tumor material and that interleukin-2 was used after infusion. It also describes screening that included physical examination, medical history, blood samples, and an ECG. These are descriptions of the intended treatment sequence; the registry record does not report how consistently each step was completed.
The listed start was 2014-11, primary completion was 2018-12-31, and status is completed. The primary outcome is titled “Number of Reported Adverse Events,” with a stated timeframe of 0-40 weeks. Its description says adverse events were collected from treatment start until 24 weeks after T-cell infusion. Those two time descriptions are not identical, and the registry record does not explain how they relate.
The record lists five outcome measures and zero analyses. It does not report a statistical analysis plan, allocation procedures beyond the single-group design, a sample-size justification, or interim analyses. The absence of a control group is especially important: outcomes can describe what occurred among participants, but they cannot establish a comparative effect against an alternative regimen.
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: One patient was enrolled in the trial and started vemurafenib, but had rapid progression of a brain metastasis and it was deemed unsafe to continue with protocol treatment. Thus, the patient was excluded before receiving T cell infusion and did not complete treatment.
Overall Study
| Stage | T Cell Therapy With Vemurafenib Pretreatment |
|---|---|
| STARTED | 13 |
| COMPLETED | 12 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | T Cell Therapy With Vemurafenib Pretreatment |
|---|---|
| Physician Decision | 1 |
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.
| Characteristic | Unit | T Cell Therapy With Vemurafenib Pretreatment |
|---|---|---|
| Participants analysed | 12 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 10 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 7 |
| Race and Ethnicity Not Collected | Participants | — |
| Stage at inclusion: M1a | Participants | 1 |
| Stage at inclusion: M1b | Participants | 1 |
| Stage at inclusion: M1c | Participants | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Reported Adverse Events, measured over 0-40 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Treatment related adverse events |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is the number of reported treatment-related adverse events. The registry description says the events were collected to assess safety of vemurafenib in combination with TIL therapy, lymphodepleting chemotherapy, and interleukin-2, according to CTCAE v. 4.0. The listed timeframe is 0-40 weeks, while the description refers to collection from treatment start until 24 weeks after T-cell infusion. The registry record does not explain this difference in time wording.
An adverse-event count can summarize how many events were recorded, but its interpretation depends on how the count is defined and collected. A total count may include repeated events in the same participant; it is not automatically the same as the number of participants who experienced at least one event. Counts also need context about observation time, event severity, attribution, and the population assessed. The registry title and description identify a count outcome, but do not report a numerical primary-outcome result, a distribution of counts, or a statistical estimate describing uncertainty.
Safety outcomes are used to characterize harms and tolerability during treatment and follow-up. They are particularly relevant in a study combining several treatment components, because adverse events can occur in the context of the regimen as a whole. In this single-group study, the endpoint can describe recorded events among participants, but it cannot determine how many would have occurred under a different treatment. Nor can the overall count alone identify which component caused a specific event.
The record also lists secondary outcomes, including objective response rate, overall survival, and progression-free survival. Their presence in the outcome list does not mean their results are reported: the registry record does not give results for those endpoints.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives an enrollment of 13 and describes a single treated group. The safety information lists 12 participants at risk for serious adverse events, of whom 4 were affected; it also lists 12 at risk for other adverse events, with 12 affected. Seven deaths are recorded in the group. These figures describe the posted safety data, but the registry record does not explain why the safety denominators are 12 when enrollment is 13, or provide enough detail to reconcile the difference. No reason for the discrepancy should be inferred.
The serious adverse-event terms with the highest listed percentages are Pyrexia at 16.7%, Pancreatitis at 8.3%, and Colitis at 8.3%. The registry record does not provide event-level listings, confidence intervals, or additional detail about timing, recurrence, severity, or attribution for these terms. The percentages therefore should be read as the registry’s reported figures, not as a complete description of the safety profile or as comparative risks.
There is no reported primary endpoint estimate for the number of adverse events and no recorded statistical analysis. The record lists zero analyses. It also does not report results for the listed secondary outcomes of treatment-related immune responses, objective response rate, overall survival, or progression-free survival. Consequently, the posted registry information does not allow an assessment of the magnitude or precision of clinical efficacy outcomes.
In general, a confidence interval expresses the range of estimates compatible with the observed data under the statistical method used. It communicates uncertainty rather than guaranteeing that a true value lies within a particular range. No confidence interval for the primary endpoint or the listed secondary outcomes is reported in the registry record, so the precision of those outcomes cannot be assessed from this record.
The lack of a control group further limits interpretation. Even if an outcome were reported, a result within this treated group would not establish what would have happened to the same participants under another treatment. It also would not separate the effects of vemurafenib, lymphodepleting chemotherapy, TIL infusion, and interleukin-2. The safety figures are descriptive observations, not comparative estimates.
The sample-size material associated with the record is described as a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It is not a description of the trial’s actual single-group design, and any resulting sample sizes are planning illustrations rather than observed power. The registry record does not report the trial’s own sample-size justification. The posted record does not provide a primary effect estimate to support a substantive assessment of efficacy or precision.
9. Statistical Methods Explained
The registry design and outcome information support a descriptive reading, not a reconstruction of a complete statistical analysis. The study is listed as single-group, with allocation not applicable and masking none. The primary endpoint is a count of reported adverse events, but no endpoint result or analysis is recorded. The statistical methods used for the trial are not reported in the registry record.
What does a single-group design allow?
In general, a single-group study describes outcomes among people receiving the study regimen. It can document events observed during treatment and follow-up, and it may inform questions about whether a treatment sequence could be carried out. It does not provide a contemporaneous group for estimating what would have happened under a different approach. Changes over time or outcomes after treatment cannot, by themselves, be attributed to the regimen with the same strength as a randomized comparison.
That limitation matters when interpreting a combination regimen. The record describes vemurafenib, lymphodepleting chemotherapy, TIL infusion, and interleukin-2 as parts of the treatment sequence. An adverse event observed after treatment does not establish which component caused it. The record lists treatment-related adverse events as an endpoint, but does not report the adjudication process or the detailed basis for attributing events to treatment.
How should a count endpoint be understood?
In general, an event count records how many events occurred under the endpoint definition. A count is distinct from the number of participants with at least one event: an individual may contribute repeated events if the counting rules allow it. Counts can also vary with the length of observation. For these reasons, interpretation often depends on the event definition, follow-up time, person-level distribution, and whether repeat events are counted.
The registry identifies the endpoint as the number of reported adverse events and describes collection according to CTCAE v. 4.0. It gives a timeframe of 0-40 weeks, while the accompanying description specifies collection from treatment start until 24 weeks after T-cell infusion. The record does not explain how the two time descriptions are reconciled, how recurrent events were handled, or how missing event information was addressed. It also does not give the primary count result or its distribution.
In general, count data can be more variable than a simple model assumes, particularly when some participants have many events and others have few. Over-dispersion means that observed variability exceeds what a chosen count model expects. If present, it can make conventional uncertainty estimates too narrow unless the analysis accounts for it. This is a general statistical consideration, not a finding about this study: the registry record does not report the event-count distribution or the model used, so it is not possible to determine whether over-dispersion was assessed.
What do the safety summaries convey?
The serious-event figures report participants at risk and participants affected, while the other-event figures provide the same kinds of counts. These are participant-level summaries, not a report of the total number of individual events. The record does not describe the denominator rules or explain why the risk groups contain 12 participants when enrollment is 13. The percentages for selected serious-event terms describe the values recorded for those terms; the record does not provide uncertainty intervals for them.
In general, a percentage without an uncertainty interval gives a point summary but not a direct account of its precision. Precision depends on the amount of information and the analysis method. In a small study, estimates can be uncertain, but the degree of uncertainty should be quantified rather than assumed. No interval estimates for these safety percentages are reported in the registry record.
What do the planning calculations mean?
The sample-size material is identified as a planning illustration, rather than the trial’s own design calculation. It describes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of an observed effect. For time-to-event calculations, the description concerns the total number of events; for other calculations, it concerns participants per arm. Those assumptions do not match the registered single-group study, which has no randomized two-arm comparison.
In general, a planning calculation asks how much information a future design might need under specified assumptions. It does not measure the power of a completed study after the fact. Sample sizes generated from an observed effect are hypothetical planning illustrations, not observed power, and their relevance depends on whether the assumptions match the future design. The registry record does not report the trial’s own sample-size justification or a planned comparative analysis.
What analysis details are absent?
The registry record lists zero analyses. It does not report a statistical analysis plan, a model for the primary count endpoint, handling of missing data, analysis populations, interim analyses, or a multiplicity strategy. It also does not report inferential results such as estimates, standard errors, confidence intervals, or p-values for the primary or secondary outcomes. Without those details, the posted information supports a description of the recorded safety figures, but not a reconstruction of the trial’s inferential analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several objectives and outcomes: treatment-related immune responses, objective response rate, overall survival, progression-free survival, and a primary adverse-event count. Having multiple outcomes raises a general statistical question about multiplicity. When many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of tests. The registry record does not report a multiplicity strategy, planned hypothesis tests, or results for the listed secondary outcomes. It is therefore not possible to determine how the study handled multiple outcomes.
Missing-data methods are also not reported in the registry record. The enrollment is 13, while the safety group lists 12 participants at risk for serious and other adverse events. The record does not explain the difference or state whether any participant lacked safety follow-up, was excluded from a particular assessment, or had incomplete data. No inference about the reason is warranted. General methods for missing information depend on why data are absent and on the outcome being analyzed; the registry record does not describe those conditions or any imputation or sensitivity analysis.
The record does not identify analysis populations for the primary or secondary outcomes. It does not state whether analyses included all enrolled participants, only participants who began treatment, or another defined group. Nor does it describe an interim-analysis plan. The absence of these details is not evidence that a particular procedure was or was not used outside the registry; it means these features are not reported in the registry record. The posted information therefore cannot establish how participant inclusion, incomplete follow-up, or multiple outcomes were handled in the study analysis.
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 |
|---|---|---|---|
| T Cell Therapy With Vemurafenib Pretreatment | 4 | 12 | 33.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| T Cell Therapy With Vemurafenib Pretreatment | 7 of 12 |
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 |
|---|---|
| T Cell Therapy With Vemurafenib Pretreatment | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | T Cell Therapy With Vemurafenib Pretreatment |
|---|---|---|
| Pyrexia | General disorders | 2 of 12 |
| Pancreatitis | Endocrine disorders | 1 of 12 |
| Colitis | Gastrointestinal disorders | 1 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | T Cell Therapy With Vemurafenib Pretreatment |
|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 12 of 12 |
| Fatique | General disorders | 12 of 12 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 12 of 12 |
| Alopecia | Skin and subcutaneous tissue disorders | 12 of 12 |
| Neutropenia | Blood and lymphatic system disorders | 12 of 12 |
| Lymphopenia | Blood and lymphatic system disorders | 12 of 12 |
| Thrombocytopenia | Blood and lymphatic system disorders | 12 of 12 |
| Myalgia | Musculoskeletal and connective tissue disorders | 11 of 12 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 10 of 12 |
| Nausea | Gastrointestinal disorders | 9 of 12 |
Serious events with the highest arm-level rate: pyrexia (16.7%), pancreatitis (8.3%), colitis (8.3%).
The safety group lists 12 participants at risk for serious adverse events and 4 affected. For other adverse events, it lists 12 at risk and 12 affected. The record also reports seven deaths. These are descriptive figures for the group; the registry record does not give enough detail to connect the death count to a particular adverse-event category, treatment component, or time interval.
The serious-event terms with the highest listed percentages are Pyrexia (16.7%), Pancreatitis (8.3%), and Colitis (8.3%). These percentages should be read as the posted values for the named terms. The registry record does not provide event counts by term, uncertainty intervals, event timing, or further information about attribution. The percentages should not be treated as comparative risks or as proof that an individual treatment component caused an event.
The number of participants at risk in the safety summaries differs from the enrollment of 13. The registry record does not explain why, so the reason should not be guessed. Also, participants affected is not the same quantity as total adverse events: one participant may experience more than one event, but the record does not describe the event-counting rules. The primary endpoint is an adverse-event count, yet no numerical result for that endpoint is reported. The listed safety figures are useful as a description of what the registry records, but they do not by themselves provide a complete account of event burden or its precision.
12. What the Result Does, and Does Not, Mean
The posted information establishes that the registry describes a completed, single-group study of vemurafenib combined with TIL therapy for metastatic melanoma. It records an enrollment of 13 and reports safety summaries for a group of 12 participants at risk. The summaries include 4 affected by serious adverse events, 12 affected by other adverse events, and seven deaths. Selected serious-event terms and their percentages are also listed. These values describe the registry record; they do not supply a comparative treatment effect.
The record does not report a numerical result for the primary endpoint, the number of reported adverse events. It also does not give results for the listed secondary outcomes, including objective response rate, overall survival, progression-free survival, or treatment-related immune responses. It therefore cannot answer how large or precise any clinical efficacy effect was. The absence of reported results in the registry record should not be interpreted as a finding of no effect.
Because there is no control group, the study cannot show how the observed outcomes compare with outcomes under another treatment. It cannot isolate the effects of the regimen’s individual components, and the adverse-event figures alone cannot establish causation. The difference between enrollment and the safety denominator is unexplained, as are the relationship between the two stated safety timeframes and the details of event counting.
In general, a confidence interval communicates uncertainty around an estimate, and a comparative analysis requires a suitable comparator. Neither a primary endpoint estimate with a confidence interval nor a comparative efficacy estimate is reported in the registry record. The record is therefore best read as a description of a treatment approach and its posted safety summaries, with important limits on what can be concluded from those summaries. It does not establish whether the combination is beneficial or harmful relative to another approach.
13. Why This Trial Matters Statistically
This study is statistically important as an example of the distinction between describing outcomes and estimating comparative effects. A single-group design can record what happened among participants receiving a complex regimen. It cannot provide a randomized comparison with another regimen, and it cannot separate the contribution of vemurafenib from lymphodepleting chemotherapy, TIL infusion, or interleukin-2. That distinction remains important even when a registry labels outcomes as safety or efficacy measures.
The primary endpoint is a count of reported adverse events, but the record does not report the count itself or its distribution. The safety summaries instead give participants at risk and affected, together with selected serious-event percentages and a death count. Those measures describe different aspects of safety and are not interchangeable. The unexplained difference between the enrollment of 13 and safety denominators of 12 illustrates why denominator definitions matter when interpreting clinical results.
The record also demonstrates why outcome listings should not be mistaken for outcome findings. Immune responses, objective response rate, overall survival, and progression-free survival appear as secondary outcomes, but their results are not reported. Without estimates and uncertainty measures, readers cannot assess the magnitude or precision of those outcomes. Statistical methods, analysis populations, missing-data handling, multiplicity procedures, and interim analyses are also not reported in the registry record.
Finally, planning calculations must be separated from the design and results of the completed study. The stated planning assumptions describe a hypothetical two-arm calculation, while the registered study is single-group. Such calculations are not observed power and do not supply missing trial results. This makes transparent reporting of design, denominators, endpoint definitions, analyses, and estimates essential to interpreting the evidence a registry record can 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 registry record leaves important details unresolved for interpreting the safety information. Enrollment is listed as 13, but the adverse-event group gives 12 participants at risk for both serious and other adverse events. The reason for this difference is not reported in the registry record. The two descriptions of the primary endpoint timeframe also differ: the listed timeframe is 0-40 weeks, while the description says collection continued from treatment start until 24 weeks after T-cell infusion. The record does not clarify how these descriptions align.
The primary endpoint is identified as a number of reported adverse events, but no numerical result, event-count distribution, or uncertainty estimate is reported. The registry record does not specify whether recurrent events were counted, how attribution was determined, or how incomplete event reporting was handled. The serious-event terms and percentages lack additional event-level context, and no uncertainty intervals are given. The record also reports seven deaths without providing a detailed account of their timing or relationship to adverse events.
The single-group design provides no concurrent comparator, limiting causal and comparative interpretation. The registry record does not report outcome results for the listed efficacy measures, nor does it provide a statistical analysis plan, analysis populations, missing-data methods, multiplicity procedures, or interim-analysis details. The sample-size description is a planning illustration with two-arm assumptions, not a report of the trial’s own sample-size justification. These limitations concern what the registry record documents; they do not establish what analyses or procedures may have been conducted but not recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Vemurafenib and TIL Therapy for Metastatic Melanoma — NCT02354690.
- Registry record last updated 2020-03-23; status last verified 2020-03.
- Results first posted 2020-02-24.
- 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
The registry record describes a completed phase 1 and phase 2, single-group study of vemurafenib with TIL therapy for metastatic melanoma. Enrollment is listed as 13. The intervention description includes vemurafenib, lymphodepleting chemotherapy, TIL infusion, and interleukin-2. The primary outcome is the number of reported treatment-related adverse events; the record gives differing descriptions of its timeframe and does not report a numerical primary endpoint result.
Safety summaries list 12 participants at risk for serious adverse events, with 4 affected; for other adverse events, 12 were at risk and 12 affected. Seven deaths are recorded. Pyrexia, Pancreatitis, and Colitis are listed among the serious-event terms with the highest percentages. Results for the listed secondary outcomes are not reported in the registry record, and the record lists zero analyses. It provides no randomized comparison, statistical analysis plan, or explanation of the safety denominators.