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 Neoadjuvant Dabrafenib, Trametinib and/or Pembrolizumab in BRAF Mutant Resectable Stage III Melanoma (NCT02858921), a randomized phase 2 study. The primary outcome is Pathological Response Rate.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02858921 |
| Phase | Phase 2 |
| Condition | Melanoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 60 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Melanoma Institute Australia |
| Results posted | Yes |
2. Clinical Question
Population
People with resectable stage IIIB/C/D melanoma with a BRAF V600 mutation were eligible for the trial; in-transit melanoma was excluded. The registry record describes melanoma as the condition and reports enrollment of 60 participants. For the primary outcome, three participants did not proceed to surgery because of distant disease progression, so pathological response was not evaluable for them.
Intervention
The trial tested two strategies involving dabrafenib and trametinib with pembrolizumab, alongside pembrolizumab alone. One strategy gave dabrafenib and trametinib first, followed by pembrolizumab. The other gave all three drugs concurrently at first, followed by pembrolizumab alone.
Comparator
The pembrolizumab-only arm serves as one comparison for the two strategies that include dabrafenib and trametinib. The record describes a randomized, parallel-group design with three treatment arms. It does not state which pairwise contrasts were designated as the primary comparison.
Primary question
The primary outcome asks how many participants had no residual melanoma cells in the planned resected tumour site or sites at surgery at week 6. This is a pathological response measure after neoadjuvant treatment. The registry record defines the measure but does not report the observed response count or proportion for any arm.
In plain terms, the trial asks whether the pathological response observed after the different pre-surgery treatment strategies differs across the randomized groups. It also includes outcomes concerning clinical response, relapse-free survival, overall survival, postoperative infection and seroma, and a surgeon’s assessment of operability. These outcomes address different aspects of the treatment course and follow-up; they are not interchangeable with the primary pathological endpoint.
The record identifies this as a phase II study, not a direct statement of what its results show. Without arm-specific primary outcome results or an estimate of the difference between groups, it is not possible to describe which strategy had a higher response rate or how precisely the groups differed. The statistical question is therefore clear, but its answer is not reported in the registry record.
3. Trial Design
This was a randomized, open-label, parallel-group phase II trial with enrollment of 60 participants. The registry record lists three arms and 20 participants at risk in each arm for the adverse-event summaries. Randomization means treatment assignment was intended to occur by chance, while open-label means masking was absent. The record does not report how the randomization sequence was generated or whether allocation was concealed.
The three strategies were sequential dabrafenib and trametinib followed by pembrolizumab; concurrent dabrafenib, trametinib and pembrolizumab followed by pembrolizumab alone; and pembrolizumab alone. In the sequential arm, dabrafenib was given at 150mg orally twice a day and trametinib at 2mg orally once a day for 1 week, followed by pembrolizumab at 2mg/kg intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. In the concurrent arm, dabrafenib at 150mg orally twice a day and trametinib at 2mg orally once a day were combined with pembrolizumab at 200mg intravenously once every 3 weeks for 6 weeks, followed by pembrolizumab alone for 46 weeks. The pembrolizumab-only arm received 200mg intravenously once every 3 weeks alone for 52 weeks.
The primary outcome was assessed from baseline to 6 weeks and concerns pathological response at surgery. The registry record also lists secondary outcomes including objective clinical response by RECIST, relapse-free survival at 12 and 24 months, overall survival at 12 and 24 months, postoperative infection and seroma, and change in the surgeon’s opinion of operability between baseline and surgery.
The record gives a study start date of 2017-11-08 and a primary completion date of 2022-01-02. It lists the study status as active, not recruiting. It does not report the sample-size justification, the intended primary contrast, or details of the statistical analysis plan.
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: Screened but found ineligible and excluded prior to randomisation n= 3
Overall Study
| Stage | Pembrolizumab ONLY | Sequential D + T, THEN Pembrolizumab | Concurrent D + T AND Pembrolizumab |
|---|---|---|---|
| STARTED | 20 | 20 | 20 |
| COMPLETED | 20 | 20 | 20 |
| NOT COMPLETED | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: A total of 3 patients did not proceed to surgery due to distant disease progression and the pathological response was not evaluable.
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 | Pembrolizumab ONLY | Sequential D + T, THEN Pembrolizumab | Concurrent D + T AND Pembrolizumab | Total |
|---|---|---|---|---|---|
| Participants analysed | 20 | 20 | 20 | 60 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 20 | 20 | 20 | 60 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 |
| Age, Continuous | Years | 56 (51 to 64) | 50 (38 to 63) | 53 (42 to 61) | 53 (38 to 64) |
| Sex: Female, Male: Female | Participants | 8 | 8 | 9 | 25 |
| Sex: Female, Male: Male | Participants | 12 | 12 | 11 | 35 |
| Race and Ethnicity Not Collected | Participants | — | — | — | 0 |
| Region of Enrollment: Australia | Participants | 20 | 20 | 20 | 60 |
| ECOG: ECOG status 0 | Participants | 20 | 20 | 19 | 59 |
| ECOG: ECOG Status 1 | Participants | 0 | 0 | 1 | 1 |
| AJCC N Stage: AJCC Stage N1b (1 clinically detected lymph node metastasis) | Participants | 13 | 11 | 14 | 38 |
| AJCC N Stage: AJCC Stage N2b (2-3 clinically detected lymph node metastases) | Participants | 3 | 6 | 3 | 12 |
| AJCC N Stage: AJCC Stage N3b (>3 lymph nodes metastases, 1 or more clinically detected or matted node) | Participants | 4 | 3 | 3 | 10 |
| BRAF Mutation Type: V600E | Participants | 16 | 16 | 17 | 49 |
| BRAF Mutation Type: V600R | Participants | 1 | 0 | 1 | 2 |
| BRAF Mutation Type: V600K | Participants | 3 | 4 | 2 | 9 |
| Lymph node sites stratified by treatment group: Neck | Participants | 7 | 0 | 4 | 11 |
| Lymph node sites stratified by treatment group: Parotid | Participants | 4 | 2 | 1 | 7 |
| Lymph node sites stratified by treatment group: Supraclavian | Participants | 0 | 1 | 0 | 1 |
| Lymph node sites stratified by treatment group: Axilla | Participants | 7 | 9 | 10 | 26 |
| Lymph node sites stratified by treatment group: Iliac | Participants | 0 | 1 | 1 | 2 |
| Lymph node sites stratified by treatment group: Inguinal | Participants | 5 | 8 | 4 | 17 |
6. Primary Endpoint
The registry lists the primary outcome as Pathological Response Rate, measured over From baseline to 6 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is pathological response rate, recorded as a count of participants. It is defined as the proportion of participants with a complete absence of residual melanoma cells in the planned resected tumour site or sites at week 6 surgery. The stated timeframe is from baseline to 6 weeks.
This endpoint measures what is found in the tumour tissue removed at surgery after neoadjuvant treatment. It differs from an imaging-based clinical response: a tumour’s visible size or appearance does not itself establish whether residual melanoma cells are present in the resected tissue. Pathological assessment therefore provides a direct tissue-based outcome for the planned operation.
Because the endpoint is a proportion, an analysis would ordinarily need to identify both the number of participants meeting the definition and the relevant denominator. For a comparison between randomized groups, the response proportions and their uncertainty would be important to interpretation. The registry record describes the endpoint but does not report arm-specific counts, proportions, group comparisons, confidence intervals, or p-values. It therefore does not establish the size or precision of any difference in pathological response.
The record notes that three participants did not proceed to surgery because of distant disease progression and that their pathological response was not evaluable. These participants cannot be classified as having a pathological response from the stated surgical tissue definition. How they were handled in any analysis, and how the remaining participants contributed to the denominator, is not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record provides the primary endpoint definition but not its observed results. No arm-specific pathological response counts or proportions are reported. There is therefore no posted estimate of the response in any group, no estimate of a difference between groups, and no confidence interval or p-value for the primary outcome. The treatment strategies cannot be ranked from the primary endpoint information in the record.
The enrollment was 60, and adverse-event summaries list 20 participants at risk in each of the three arms. Those safety denominators do not fill the gap in the primary endpoint results. In particular, the record states that three participants did not proceed to surgery because of distant disease progression and were not evaluable for pathological response. It does not state the number evaluable in each arm or the analysis population used for the endpoint.
The secondary outcomes cover several different questions. Objective clinical response is distinct from pathological response. Relapse-free and overall survival at 12 and 24 months concern events over follow-up, while postoperative infection and seroma concern complications after surgery. The record lists these outcomes but does not report their observed values. A list of outcomes is not evidence that a particular result was favorable, unfavorable, or statistically distinguishable.
General statistical interpretation depends on both the estimated effect and its uncertainty. A confidence interval describes a range of values compatible with the data under the analysis assumptions; a narrow interval indicates greater precision than a wide one. Since no primary effect estimate or interval is reported, the precision of the trial’s primary comparison cannot be assessed. The record also does not provide a primary p-value, so statistical significance cannot be evaluated.
The registry record states that the trial was randomized and open-label, but those design labels alone do not answer the outcome question. Randomization supports comparisons between assigned groups when the analysis and follow-up preserve the benefits of the design. Open-label treatment can matter for outcomes involving judgement or care decisions, although the record does not report whether or how this was addressed. Pathological response is based on tissue assessment, but the record does not describe assessor masking or assessment procedures beyond the endpoint definition.
Planning calculations based on an observed effect are not a substitute for a reported trial result. Such calculations can illustrate the participant numbers needed under specified assumptions, but they do not indicate the probability that this trial found an effect. The record’s stated planning assumptions are not the trial’s sample-size justification, and the planning illustrations should not be read as observed power. The primary outcome conclusions remain unavailable because the outcome results and their analysis are not reported in the registry record.
9. Statistical Methods Explained
Several statistical ideas help clarify what the registry record does and does not establish. The primary endpoint is binary at the participant level: a participant either meets the stated definition of complete absence of residual melanoma cells at the planned resected site or sites, or does not. A count of participants with an event is a way to record this kind of outcome. To compare groups, counts need to be interpreted in relation to the number of participants analyzed in each group.
What does a response proportion represent?
A proportion describes the share of a defined group who meet an outcome definition. For this trial, that would mean relating the number with pathological response to the relevant analysis denominator. The denominator matters because participants who are not assessed cannot simply be assumed to have responded or not responded. Three participants did not proceed to surgery because of distant disease progression and are explicitly described as not evaluable for the primary outcome. The record does not report the analysis rule for these participants or the arm-specific denominators used to calculate any response proportions.
For a randomized trial, comparisons may be expressed as differences between group proportions or through another stated effect measure. The measure chosen affects how the result is described, but the registry record does not report a primary contrast or effect estimate. It also does not report confidence intervals or p-values. Consequently, it is not possible to assess either the direction and magnitude of a primary effect or the uncertainty around it.
Why does uncertainty matter?
General explanation: a confidence interval communicates uncertainty around an estimate. It is not a guarantee that the true effect lies in the interval, but it shows which values are reasonably compatible with the data under the method’s assumptions. A point estimate alone can be misleading if it is imprecise. Here, no primary point estimate or interval is reported, so the precision of the primary comparison cannot be judged. A p-value, if reported, would address compatibility with a specified null hypothesis under an analysis model; it would not by itself describe the size, clinical importance, or precision of an effect.
The registry record lists one analysis, but it does not identify the statistical method, the contrast, the handling of missing outcomes, or the adjustment strategy. The record also does not report whether the endpoint was analyzed according to randomized assignment or among participants with evaluable surgical pathology. These are important distinctions for interpretation, not details that can be inferred from a randomized design alone.
What is multiplicity?
General explanation: multiplicity arises when several outcomes, treatment comparisons, time points, or analyses are examined. If each is tested separately, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for the collection of tests. This trial has three arms and the registry record lists 22 outcome measures, including several secondary outcomes and more than one survival time point. The record does not describe a multiplicity adjustment, a hierarchy among outcomes, or which comparisons were prespecified as confirmatory. The number of listed outcomes alone does not establish how many tests were performed.
For outcomes measured over time, estimates can depend on how follow-up, censoring, and event definitions are handled. General explanation: time-to-event methods use information about when events occur and about participants who have not yet had an event by the end of observed follow-up. Their interpretation depends on the analysis method and assumptions. The registry record lists relapse-free and overall survival outcomes at 12 and 24 months, but it does not report event counts, estimates, confidence intervals, censoring rules, or the analysis method for these outcomes.
How should planning illustrations be read?
The planning assumptions described for the sample-size illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe detecting a stated fraction of the observed effect. For time-to-event outcomes, the illustrations use a total number of events; for other outcomes, they express participants per arm. These are planning illustrations computed from an observed effect, not the trial’s own design justification. No sample-size justification is reported in the registry record, and the illustrations are not observed power. No numerical illustration values are available in the record, so none can be interpreted as a trial result.
General explanation: over-dispersion occurs when observed variability exceeds what a model assumes. It can make standard errors too small if the model does not account for the extra variability. This concept is relevant in some count-data analyses, but the primary endpoint is recorded as a participant count for a binary response, and the registry record does not report an over-dispersion model or any fitted statistical model. It would be inappropriate to infer that such a method was used.
In short, the registry record supplies a clear clinical definition of the primary endpoint and describes a three-arm randomized design. It does not provide the outcome data or statistical details needed to reproduce or evaluate a primary group comparison. General statistical principles explain what those details would contribute, but they cannot replace the missing estimates and analysis information.
10. Multiplicity, Missing Data and Analysis Populations
The trial has three treatment arms and the registry record lists 22 outcome measures. The secondary outcomes include clinical response, relapse-free survival and overall survival at two time points, postoperative complications, and an assessment of operability. Examining several outcomes and possible group comparisons raises a multiplicity question: the more hypotheses tested, the more important it is to know which comparisons were planned and whether any adjustment or testing hierarchy was specified. The record does not report a multiplicity strategy, a hierarchy of endpoints, or which treatment contrasts were prespecified for confirmatory interpretation.
The presence of multiple listed outcomes does not prove that every possible comparison was analyzed. The record lists one analysis but does not describe its method, target contrast, or role in relation to the other outcomes. It also does not report whether analyses were exploratory or confirmatory. These details are not reported in the registry record.
Missing outcome information is especially relevant to the primary endpoint. Three participants did not proceed to surgery because of distant disease progression, and pathological response was not evaluable for them. The record does not state how these participants were treated in the analysis, whether missing outcomes were handled by imputation, or whether a sensitivity analysis was conducted. It does not report other missing-data patterns or the number of evaluable participants in each arm.
The analysis population is also not described. The record does not specify whether the primary analysis followed randomized assignment, included only participants with evaluable pathology, or used another population definition. It does not report protocol deviations or exclusions. Without these details, the effect of missing outcomes and analysis choices on the primary comparison cannot be assessed.
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 |
|---|---|---|---|
| Sequential D + T, THEN Pembrolizumab | 6 | 20 | 30.0% |
| Concurrent D + T AND Pembrolizumab | 11 | 20 | 55.0% |
| Pembrolizumab ONLY | 1 | 20 | 5.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sequential D + T, THEN Pembrolizumab | 3 of 20 |
| Concurrent D + T AND Pembrolizumab | 2 of 20 |
| Pembrolizumab ONLY | 4 of 20 |
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 |
|---|---|
| Sequential D + T, THEN Pembrolizumab | 19 of 20 |
| Concurrent D + T AND Pembrolizumab | 20 of 20 |
| Pembrolizumab ONLY | 17 of 20 |
Most frequent serious adverse event terms
| Event term | Organ system | Sequential D + T, THEN Pembrolizumab | Concurrent D + T AND Pembrolizumab | Pembrolizumab ONLY |
|---|---|---|---|---|
| Hepatitis | Hepatobiliary disorders | 2 of 20 | 2 of 20 | 0 of 20 |
| Pyrexia | General disorders | 0 of 20 | 3 of 20 | 0 of 20 |
| ALT increased | Investigations | 1 of 20 | 2 of 20 | 0 of 20 |
| AST increased | Investigations | 0 of 20 | 2 of 20 | 0 of 20 |
| GGT increased | Investigations | 2 of 20 | 0 of 20 | 0 of 20 |
| Lipase increased | Investigations | 1 of 20 | 1 of 20 | 0 of 20 |
| Wounbd infection | Infections and infestations | 1 of 20 | 0 of 20 | 1 of 20 |
| Diarrhoea | Gastrointestinal disorders | 0 of 20 | 0 of 20 | 1 of 20 |
| Guillain-Barre syndrome | Nervous system disorders | 0 of 20 | 1 of 20 | 0 of 20 |
| Arthritis | Musculoskeletal and connective tissue disorders | 1 of 20 | 0 of 20 | 0 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sequential D + T, THEN Pembrolizumab | Concurrent D + T AND Pembrolizumab | Pembrolizumab ONLY |
|---|---|---|---|---|
| Fatigue | General disorders | 14 of 20 | 14 of 20 | 13 of 20 |
| Rash | Skin and subcutaneous tissue disorders | 7 of 20 | 7 of 20 | 9 of 20 |
| Pyrexia | General disorders | 4 of 20 | 17 of 20 | 0 of 20 |
| Pruritis | Skin and subcutaneous tissue disorders | 8 of 20 | 2 of 20 | 7 of 20 |
| Nausea | Gastrointestinal disorders | 6 of 20 | 8 of 20 | 3 of 20 |
| Chills | General disorders | 4 of 20 | 10 of 20 | 0 of 20 |
| Viiligo | Skin and subcutaneous tissue disorders | 3 of 20 | 0 of 20 | 5 of 20 |
| Seroma | Injury, poisoning and procedural complications | 2 of 20 | 2 of 20 | 0 of 20 |
| Wound infection | Injury, poisoning and procedural complications | 2 of 20 | 0 of 20 | 2 of 20 |
| Influenza type illness | General disorders | 0 of 20 | 1 of 20 | 1 of 20 |
Serious events with the highest arm-level rate: pyrexia (15.0%), alt increased (10.0%), ast increased (10.0%), ggt increased (10.0%), hepatitis (10.0%).
The registry record lists serious adverse events, other adverse events, and deaths separately for each treatment arm. For serious adverse events, 6 of 20 participants were affected in the sequential dabrafenib and trametinib then pembrolizumab arm, 11 of 20 in the concurrent combination arm, and 1 of 20 in the pembrolizumab-only arm. For other adverse events, the corresponding counts were 19 of 20, 20 of 20, and 17 of 20. These are counts of affected participants, not a measure of how many events each participant experienced.
The death counts listed by arm are 3, 2, and 4, respectively. The record does not state in this summary whether these deaths were judged related to treatment, nor does it give their causes or timing. The counts should not be interpreted as treatment-caused deaths.
The registry also lists serious adverse event terms with percentages: Pyrexia, 15.0%; ALT increased, 10.0%; AST increased, 10.0%; GGT increased, 10.0%; Hepatitis, 10.0%; and Diarrhoea, 5.0%. These terms are presented without an arm-specific breakdown in the listed summary. The record does not specify whether the percentages count participants or events for each term, so their precise denominator and counting basis should not be inferred.
Safety comparisons require attention to definitions, follow-up duration, event severity, and attribution. The listed counts describe the registry’s summaries, but the record does not provide a comparative statistical analysis of safety or enough detail to determine whether differences between arms are meaningful.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a randomized, open-label phase II study of three neoadjuvant strategies in resectable BRAF V600 mutant stage III melanoma. It defines pathological response as complete absence of residual melanoma cells in the planned resected tumour site or sites at week 6 surgery. It also reports that three participants did not proceed to surgery because of distant disease progression and were not evaluable for that endpoint.
Those details describe the design and the outcome being assessed; they do not reveal the primary outcome result. Arm-specific response counts, proportions, comparisons, confidence intervals, and p-values are not reported in the registry record. It is therefore not possible to say which arm had the highest response, whether the groups differed, or how precise any difference was. The presence of a defined endpoint is not evidence of a particular outcome.
The registry record also lists secondary outcomes and adverse-event summaries. The secondary outcomes cover clinical response, survival at specified time points, postoperative infection and seroma, and operability. Their definitions and listing do not supply their results. Adverse-event counts and the listed event terms provide descriptive safety information, but the record does not report a comparative safety analysis or establish causal attribution for the listed deaths.
General interpretation requires distinguishing evidence of an observed result from evidence about its uncertainty. A result may be compatible with a range of effects, and that range depends on the data and analysis. Without the primary estimate and its uncertainty, neither statistical evidence for a between-arm difference nor its size can be evaluated. The randomized design is a feature of how the trial was structured, not a substitute for outcome reporting.
Nothing in this record summary establishes whether any treatment strategy is effective or ineffective. It also cannot establish equivalence among the strategies: absence of a reported difference is not evidence that differences are absent. A defensible conclusion about comparative outcomes would require the relevant estimates, analysis populations, and statistical methods, which are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically interesting because it compares three strategies rather than a single treatment with a single control. The strategies differ in whether dabrafenib and trametinib are given before or alongside pembrolizumab, or whether pembrolizumab is given alone. A three-arm randomized design can address more than one treatment question, but interpretation depends on knowing which comparisons were planned and how uncertainty was handled.
The primary endpoint also illustrates why endpoint definitions and analysis populations matter. Pathological response is defined by tumour tissue at surgery, while three participants did not reach surgery because of distant disease progression. Those participants are not evaluable under the stated tissue-based definition. How this situation was handled analytically can affect the interpretation of a response proportion, but the registry record does not report the analysis rule or arm-specific denominators.
The range of listed secondary outcomes brings further statistical considerations. Clinical response, survival, surgical complications, and operability capture different domains and may have different data structures and follow-up needs. Multiple outcomes and time points can create multiplicity concerns, and the registry record does not describe how these were addressed. This is a useful example of why outcome lists alone are not enough to understand the inferential plan.
The record gives a study design and outcome definitions, along with descriptive adverse-event counts, but does not report the primary outcome results or inferential statistics. It therefore demonstrates an important distinction in clinical-trial reading: a registered question, a completed measurement, and a reported analysis are separate things. Without the outcome estimates and methods, the scientific question remains specified but unanswered by the registry record.
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 important trial-specific limitation for interpreting the registry record is the absence of reported primary outcome results. No response counts, proportions, group contrasts, confidence intervals, or p-values are given. The primary endpoint is therefore defined but cannot be assessed comparatively from the registry record.
Three participants did not proceed to surgery because of distant disease progression and were not evaluable for pathological response. The record does not report their distribution across arms or how their missing endpoint values were handled. It also does not give the number of participants with evaluable pathology by arm or identify the analysis population. This leaves uncertainty about the denominator and the influence of non-evaluable outcomes on any analysis.
The trial is open-label, and the record does not describe whether pathological assessors were masked to treatment assignment. It also does not report randomization procedures, allocation concealment, treatment adherence, protocol deviations, or losses to follow-up. These omissions do not establish that a specific bias occurred, but they limit assessment of how the design was implemented.
The registry record lists multiple secondary outcomes and three arms but does not report the prespecified treatment contrasts, a statistical analysis plan, or any multiplicity approach. The method used for survival outcomes and the handling of censoring are not reported. Sample-size justification is also not reported; the planning illustrations described in the record are not the trial’s own design justification.
The safety summary gives affected-participant counts and selected serious adverse event terms, but does not provide arm-specific detail for the listed terms, event timing, attribution, or a comparative safety analysis. The deaths are listed by arm without causes or treatment-relatedness in this summary. These limitations concern what can be concluded from the registry record, not necessarily what may be available elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Neoadjuvant Dabrafenib, Trametinib and/or Pembrolizumab in BRAF Mutant Resectable Stage III Melanoma — NCT02858921.
- Registry record last updated 2026-08-24; status last verified 2026-07.
- Results first posted 2026-08-24.
- 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
NCT02858921 is a randomized, open-label, parallel-group phase II study of neoadjuvant dabrafenib, trametinib and/or pembrolizumab in resectable BRAF V600 mutant stage IIIB/C/D melanoma, excluding in-transit melanoma. The record lists enrollment of 60 participants in three treatment arms and a primary endpoint of pathological response assessed at week 6 surgery.
The primary outcome is defined as complete absence of residual melanoma cells in the planned resected tumour site or sites. Three participants did not proceed to surgery because of distant disease progression and were not evaluable for pathological response. The registry record does not report arm-specific primary response results or the statistical analysis needed to compare the arms.
Secondary outcomes include clinical response, relapse-free and overall survival, postoperative infection and seroma, and operability. Descriptive adverse-event counts are reported by arm, but the registry record does not provide a comparative safety analysis. The study status is active, not recruiting; the listed start date is 2017-11-08 and primary completion date is 2022-01-02.