A Study of Safety and Clinical Activity of Immunotherapy Plus Chemotherapy in Metastatic Melanoma Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Safety and Clinical Activity of Immunotherapy Plus Chemotherapy in Metastatic Melanoma Patients (NCT00849875), a na phase 2 study. The primary outcome is Number of Seroconverted Patients for Melanoma Antigen (Anti-MAGE-A3).

2. Clinical Question

The registry’s brief summary describes the study’s purpose as assessing the ability of patients with progressive metastatic cutaneous melanoma to develop an immune response to an immunotherapeutic product given with dacarbazine, while also evaluating safety. The primary endpoint makes the immune-response part of that purpose explicit by defining seroconversion through an anti-MAGE-A3 antibody concentration threshold. Several secondary outcomes concern tumor response, stable or mixed disease, treatment failure, and progression-free survival, including outcomes by gene signature. However, their numerical results are not reported in the registry record available for this analysis.

The combination was evaluated in a Phase 2, single-group study. Without a comparator, observed antibody responses or clinical outcomes cannot be separated from the natural course of disease, effects of dacarbazine, or other influences. The clinical question is therefore descriptive: what response and safety outcomes were recorded among treated participants? The registry record does not provide the numerical primary endpoint result needed to describe the frequency of seroconversion.

3. Trial Design

This was a Phase 2, single-group study of immunotherapeutic GSK2132231A in association with dacarbazine for patients with unresectable and progressive metastatic cutaneous melanoma. The registry lists 48 participants as enrolled. The study began on 2009-05-26, had a primary completion date of 2014-11-17, and is listed as terminated. The reason for termination is not reported in the registry record.

All patients were assigned to the same treatment group. The arm description specifies 24 injections of GSK2132231A combined with 8 cycles of dacarbazine, with dacarbazine given at the beginning of treatment. Allocation is listed as not applicable, and masking as none. No randomized comparison or control arm is described. Consequently, the design can describe outcomes in the treated group but cannot estimate a treatment contrast against a concurrent control group.

The primary outcome was the number of seroconverted patients for melanoma antigen anti-MAGE-A3, assessed after Dose 4 at Week 13. The registry defines the Total Treated population as patients who received at least one dose of GSK2132231A. It does not report the number of participants who met that definition or the number included in the endpoint analysis. Although 48 participants are listed as enrolled, enrollment alone does not establish how many received treatment or contributed data at the specified assessment.

The registry lists 38 outcome measures and several secondary outcomes involving objective tumor response, stable disease, mixed response, treatment failure, and progression-free survival. Numerical results for those outcomes are not reported in the registry record. No analysis records are reported. The planned statistical analysis, sample-size justification, interim analyses, and reasons for stopping the study are not reported in the registry record.

The brief summary refers to GSK1572932A, while the official title, intervention listing, and arm description refer to GSK2132231A. This difference in product naming is present in the registry record; its explanation is not reported.

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: During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the patients and signing informed consent forms.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Total Treated population included all patients who have received at least one dose of the GSK2132231A product.

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 Number of Seroconverted Patients for Melanoma Antigen (Anti-MAGE-A3), measured over Post Dose 4 at Week 13 (W13)..

The primary endpoint is a count of patients who seroconverted for anti-MAGE-A3 antibodies after Dose 4 at Week 13. The registry defines seroconversion as an antibody concentration above the assay cut-off in a patient whose concentration was below the cut-off before treatment began. It further identifies seroconverted patients as those with anti-MAGE-A3 antibody concentrations ≥ 27. The registry gives the unit as patients and the measure type as a number, so the endpoint is a count rather than a continuous antibody concentration or a time-to-event measure.

This endpoint was used to assess whether an antibody response could be detected after the immunotherapeutic treatment. A threshold-based definition turns the laboratory measurement into a yes-or-no classification for each participant. Such a definition can make the outcome easier to interpret as a count, but it also means the result depends on the stated cut-off and the availability of both baseline and post-treatment measurements. The registry record does not report assay details beyond the definition, nor does it report how missing baseline or Week 13 measurements were handled.

The endpoint is about an immune response, not a direct measure of tumor shrinkage, disease progression, or survival. Those topics appear among the secondary outcomes, but their numerical results are not reported in the registry record. The number of seroconverted patients and the corresponding analyzed denominator are also not reported in the registry record, so the frequency of the endpoint cannot be described from the recorded information available for this analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: A binary endpoint classifies each participant into one of two categories, such as meeting or not meeting a seroconversion definition. The study’s primary endpoint is expressed as a number of patients meeting the antibody-response definition. A count is useful for reporting how many participants crossed a prespecified threshold, but interpretation also depends on how many participants were assessed. A count without its analysis denominator cannot establish the observed proportion.

The registry defines the primary population as patients who received at least one dose of GSK2132231A. It does not report the number of treated participants or the number with evaluable Week 13 results. These populations need not be assumed to match the enrollment count. In general, a participant may be enrolled but not receive treatment, or may not have an assessment at the endpoint time. Whether either occurred in this study is not reported in the registry record.

What does a confidence interval add?

General statistical explanation: A confidence interval expresses uncertainty around an estimate. For a binary outcome, an interval around a proportion can show how much the estimate might vary because only a finite group of participants was observed. An interval is not a guarantee that the true value lies within its limits, and it does not correct for bias caused by missing outcomes or a non-comparative design. No confidence interval for the primary endpoint is reported in the registry record, and the missing numerical endpoint result means its precision cannot be assessed.

General statistical explanation: An estimate should be read alongside its denominator and the method used to calculate uncertainty. Different interval procedures can behave differently, particularly when event counts or sample sizes are limited. The registry record does not report an interval method or a statistical analysis for the primary endpoint. Therefore, no particular method should be attributed to the investigators.

Why does the single-group structure matter?

General statistical explanation: A single-group study can describe outcomes among people receiving a treatment regimen. It does not, by itself, provide the counterfactual outcome that the same participants would have experienced under an alternative regimen or no treatment. A comparison with historical experience, if one were attempted, would depend on assumptions about comparability and would not be equivalent to a randomized concurrent control. No such comparison is reported in the registry record. In this study, the combination regimen also means a response cannot be attributed separately to GSK2132231A or dacarbazine from the design alone.

General statistical explanation: Masking is a design feature that can affect how outcomes are assessed or reported, especially for outcomes involving judgment. The registry lists masking as none. This describes the recorded design; the registry does not provide further details about endpoint assessment procedures or safeguards against assessment bias.

How should planning calculations be read?

General statistical explanation: A sample-size calculation can illustrate how many participants might be needed under specified assumptions about the effect to detect, significance level, allocation, and statistical model. It does not describe the number of participants actually observed, and it is not observed power. The planning illustrations associated with this study are described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with target effects expressed as fractions of an observed effect. Those are planning assumptions, not evidence that the trial used a two-arm design: the registry describes one treatment group and no control group. The registry’s own sample-size justification is not reported in the registry record. The observed endpoint effect needed to interpret such illustrations is also not reported in the endpoint information available for this analysis.

General statistical explanation: A two-arm planning illustration usually answers a hypothetical question about the number of participants per arm under its assumptions. It should not be read as a recommendation for this study or as a retrospective test of whether the study had enough participants. Because the actual design was single-group, the hypothetical equal-allocation setup does not describe the trial’s allocation. Sample-size planning also cannot substitute for reporting the observed count, denominator, and uncertainty for the primary endpoint.

What about other endpoint types?

General statistical explanation: The listed secondary outcomes include binary response categories and time-to-event outcomes. A time-to-event analysis uses both the timing of an event and follow-up information; participants without an event by the end of observation may contribute partial information. Progression-free survival and time to treatment failure therefore require definitions of the event, censoring, and analysis population. Those statistical details are not reported in the registry record. The listed outcome names alone are not enough to reconstruct an analysis or interpret an effect estimate.

General statistical explanation: Analyses by gene signature would involve subgroup information, and subgroup estimates can be less precise than an overall estimate. The registry lists such outcomes but does not report subgroup sizes, results, or the analysis plan. The registry record also does not report whether any interim analyses were planned or conducted. No claims about modeling, adjustment, hypothesis testing, or handling of repeated assessments can be made from the listed outcomes alone.

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("GSK2132231A GROUP", "GSK2132231A GS+ Group", "GSK2132231A GS- Group", "GSK2132231A GS Unknown Group")
n      <- c(28, 19, 8, 1)
events <- c(28, 19, 8, 1)
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  GSK2132231A GROUP  28  28  100.0  87.7  100.0  87.9  100.0  88.1  99.9
ARM  GSK2132231A GS+ Group  19  19  100.0  82.4  100.0  83.2  100.0  83.2  99.9
ARM  GSK2132231A GS- Group  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  GSK2132231A GS Unknown Group  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including tumor response categories, duration of stable disease, treatment failure, and progression-free survival in the overall population or by gene signature. When many outcomes or subgroup analyses are examined, the chance of finding an apparently notable result by chance can increase. General statistical explanation: multiplicity procedures can control or describe this issue, but their use depends on the hypotheses and analysis plan. The statistical plan and any multiplicity adjustment are not reported in the registry record. No analysis records are reported, so there is no posted set of outcome tests from which to determine how multiple findings were handled.

The record does not report how missing endpoint data were handled, whether participants who stopped treatment remained in the analysis, or whether an imputation method was used. It also does not report the number with baseline antibody measurements or Week 13 assessments. These details matter because the primary endpoint definition relies on both a below-cut-off baseline concentration and a post-treatment concentration meeting the stated threshold. Without an analysis denominator and missing-data description, the extent to which unavailable measurements could affect the reported count cannot be assessed.

The stated Total Treated population includes patients who received at least one dose of GSK2132231A. The number meeting that definition is not reported in the registry record. The record also does not describe an intention-to-treat population or other analysis populations. Enrollment of 48 does not establish the number in any endpoint analysis. The registry’s approach to participants without evaluable results, protocol deviations, or withdrawal is not reported.

The trial is listed as terminated, but the reason and timing of termination relative to outcome collection are not reported in the registry record. No interim analysis information is reported. These omissions limit assessment of whether the listed outcomes and analyses were prespecified and whether all relevant participants and assessments were included.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthenia (4.2%), endometrial adenocarcinoma (2.1%), palpitations (2.1%), neutropenia (2.1%), pancytopenia (2.1%).

The registry safety summary lists 48 participants at risk for serious adverse events and 10 participants affected. It also lists 48 participants at risk for other adverse events and 48 affected. These are participant counts, not event counts: one participant may have experienced more than one event. The registry record does not provide further detail about event timing, duration, severity grading, or whether events were considered related to treatment.

The listed serious adverse-event terms and percentages are asthenia, 4.2%; endometrial adenocarcinoma, 2.1%; palpitations, 2.1%; neutropenia, 2.1%; pancytopenia, 2.1%; and thrombocytopenia, 2.1%. These are the entries reported in the safety summary, not a complete account of all possible clinical events. The record does not establish from these figures alone whether events were caused by GSK2132231A, dacarbazine, the combination, or other factors.

The study has no control group, so the safety counts cannot be compared with a concurrent group receiving another treatment or no treatment. The registry does not report a death count in the available safety information. These limitations mean that the entries describe reported events among participants at risk; they do not estimate comparative safety or determine causality.

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

The registry record establishes that a Phase 2, single-group study was conducted to assess an anti-MAGE-A3 antibody response and safety during treatment with GSK2132231A and dacarbazine. It specifies the primary endpoint’s timing and seroconversion threshold, lists secondary clinical outcomes, and records enrollment of 48. It also lists the study as terminated. These registry entries describe the study’s purpose and design, not the magnitude of its findings.

The numerical result for the primary endpoint is not reported in the registry record. Neither the number of seroconverted participants nor the endpoint analysis denominator is reported. As a result, the recorded information does not establish how often the defined antibody response occurred, how precise an estimate might be, or how it relates to any prespecified target. Numerical results for the listed secondary outcomes are also not reported in the registry record.

Even if a response count were available, this design would support a description of outcomes in the treated group rather than a causal comparison. There is no randomized or concurrent control group, and the regimen combines an immunotherapeutic product with chemotherapy. The design cannot separate the effects of the two treatments or account for what would have happened to the same participants under a different regimen.

The primary endpoint is an immune-response measure. It is not itself a measure of tumor response, progression-free survival, or overall survival. The registry lists clinical outcomes relevant to disease status and progression, but their numerical findings are not reported. The endpoint definition therefore cannot be used to infer clinical benefit, and the safety counts cannot establish comparative risk or causation.

The record also does not state why the study was terminated, whether endpoint data collection was complete, or how missing information and multiple outcomes were handled. These omissions leave important uncertainties about the analysis and its completeness. The most defensible reading is limited: the registry documents a single-group combination study and its planned immune-response endpoint, while the numerical primary and secondary efficacy findings and several analysis details are not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates an important distinction between an outcome definition and an outcome result. A registry can describe exactly what counts as seroconversion, identify when it is assessed, and define the population in which it is intended to be measured. Those details improve clarity about the question researchers planned to ask. But without the number meeting the definition and the number assessed, the endpoint cannot be interpreted quantitatively.

The case also shows why design structure matters when reading clinical evidence. A single-group study can document what happened among treated participants, but it does not provide a concurrent comparison for separating treatment effects from other influences. That limitation is particularly relevant to a combination regimen, where the contribution of each component cannot be isolated by the design described in the registry.

The registry lists immune response as the primary endpoint and clinical outcomes such as tumor response and progression-free survival as secondary outcomes. Keeping those concepts distinct prevents an antibody-response measure from being mistaken for a direct clinical outcome. The record’s secondary outcome listings signal that additional questions were contemplated, but numerical findings and analysis details are not reported.

Finally, the study’s terminated status, missing endpoint results, and unreported analysis details illustrate why registry status and results must be read separately. Termination does not explain what happened to data collection or why the study stopped. A clear account of outcomes, denominators, missing data, and analysis methods is needed to interpret findings; those details are not reported in the registry record. The statistical lesson is not a conclusion about the treatment, but a reminder that design, endpoint definition, and result reporting each answer different questions.

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 trial has no control group and is described as single-group, with allocation not applicable and no masking. This prevents a like-for-like comparison and limits causal interpretation. Because the treatment includes GSK2132231A and dacarbazine, the design also cannot distinguish the effects of the two components. These are features of the recorded design rather than evidence about the direction or size of any treatment effect.

The primary endpoint’s numerical result and analyzed denominator are not reported in the registry record. Enrollment of 48 does not establish how many participants received at least one dose, had baseline antibody data, or completed assessment after Dose 4 at Week 13. The registry does not report how missing measurements were handled. This limits interpretation of the endpoint even though its threshold-based definition is described.

The study is listed as terminated, but the reason for termination and the completeness of outcome collection are not reported. The registry does not report the statistical analysis plan, sample-size justification, interim analyses, multiplicity handling, or analysis populations beyond the definition of the Total Treated population. It lists 38 outcome measures, but numerical results for the primary and listed secondary outcomes are not reported in the registry record.

The safety summary provides participant counts and selected serious adverse-event terms, but does not report additional detail on timing, event-level counts, treatment relationship, or comparative rates. The death count is not reported in the registry record. Finally, the brief summary uses GSK1572932A, while other registry descriptions use GSK2132231A; the reason for this naming difference is not reported.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Safety and Clinical Activity of Immunotherapy Plus Chemotherapy in Metastatic Melanoma Patients — NCT00849875.
• Registry record last updated 2017-07-12; status last verified 2017-06.
• Results first posted 2017-03-30.
• 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

NCT00849875 is a Phase 2, single-group study of GSK2132231A with dacarbazine in patients with unresectable and progressive metastatic cutaneous melanoma. The registry lists 48 participants enrolled, a start date of 2009-05-26, a primary completion date of 2014-11-17, and a status of terminated. The reason for termination is not reported in the registry record.

The primary endpoint counted patients with anti-MAGE-A3 seroconversion after Dose 4 at Week 13, using the stated concentration threshold of ≥ 27. The numerical endpoint result and analysis denominator are not reported in the registry record. The study had one treatment group and no control group. Safety entries list 10 participants with serious adverse events among 48 at risk, and 48 participants with other adverse events among 48 at risk. Numerical findings for the listed secondary outcomes and the death count are not reported in the registry record.