Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer (NCT02499835), a randomized phase 1, phase 2 study. The primary outcome is Incidence of Adverse Events, Using the National Cancer Common Terminology Criteria, Version 4.

2. Clinical Question

The main statistical question is descriptive: how many adverse events were recorded in each treatment arm over the stated observation period, and what can those counts tell readers about safety? A count of events is not the same as a count of affected participants. One person can experience multiple events, and the registry describes totals per arm rather than a rate adjusted for time at risk.

The secondary immune outcomes ask whether participants had PAP-specific immune or T-cell responses. Those outcomes can offer biological information about the vaccine, but they do not replace the primary safety endpoint or establish a clinical treatment effect. The registry record does not report a sponsor analysis comparing the arms on these outcomes.

3. Trial Design

This was a randomized, parallel-group pilot trial listed as Phase 1 and Phase 2. Masking was none. Enrollment was 66, and the record marks the study as completed. The trial included Arm I, Arm II, Extended Treatment Arm III, and Extended Treatment Arm IV.

Arm I combined intradermal pTVG-HP vaccination every other week on days 1, 15, 29, 43, 57, and 71 with pembrolizumab intravenously every 3 weeks on days 1, 22, 43, and 64. Arm II used the same vaccine schedule, with pembrolizumab beginning on day 85 and then given every 3 weeks on days 106, 127, and 148. These first arms therefore differed in the timing of pembrolizumab relative to vaccination.

Extended Treatment Arm III used pTVG-HP with rhGM-CSF every 3 weeks, for a maximum of 16 doses, and pembrolizumab every 3 weeks, for a maximum of 16 doses, beginning on day 1 after the first vaccination. Extended Treatment Arm IV used the vaccine every 2 weeks, for a maximum of 24 doses, and pembrolizumab every 4 weeks, for a maximum of 12 doses, also beginning on day 1 after the first vaccination. The extended-arm descriptions specify pTVG-HP (100 μg), rhGM-CSF (208 μg), and pembrolizumab 2 mg/kg, with a maximum dose of 200 mg.

The primary completion date was 2021-08-09, and the study start date was 2015-07-01. The registry record does not report the randomization procedure, allocation concealment, a sample-size justification, or a prespecified statistical analysis plan. The arm sizes posted with the primary outcome were 13, 13, 20, and 20, respectively.

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

Reasons for not completing this period:

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 Incidence of Adverse Events, Using the National Cancer Common Terminology Criteria, Version 4, measured over Up to 23 months (Up to 12 months after completion of study treatment).

The primary endpoint was the incidence of adverse events using the National Cancer Common Terminology Criteria, Version 4. Its registry description says toxicities would be summarized by type and total events calculated per arm. The stated timeframe was up to 23 months, described as up to 12 months after completion of study treatment.

The posted primary outcome values are event counts: 117 for Arm I, 173 for Arm II, 163 for Extended Treatment Arm III, and 225 for Extended Treatment Arm IV. These are totals, not the number of participants who experienced an event. Because a participant may have more than one adverse event, an event total cannot be read as a participant risk or as the proportion of participants affected.

Event counts are useful for describing the recorded burden of adverse events. For interpretation, however, they need context: the number of participants observed, the time each participant remained under observation or treatment, and the types and severity of events. The registry gives arm sizes and a broad observation window, but does not provide an exposure-adjusted event rate or a statistical comparison for this endpoint. Consequently, the counts describe what was recorded in each arm; they do not by themselves establish that one schedule is safer than another.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry’s primary endpoint is a count outcome. A count records how many events occurred, while a participant count records how many people experienced at least one event. These answer different questions: if one participant experiences several events, each can contribute to the event total, but that participant contributes once to the count of affected participants. The primary endpoint values are event totals per arm, while the serious and other adverse-event summaries report participants affected.

Why exposure matters for event counts

General statistical explanation: an event count is easier to compare when the groups have similar observation time and opportunity for events. If participants are followed for different lengths of time, a group with more observed time may accumulate more events even if its event rate is similar. An event rate uses a time-at-risk denominator; the registry record does not report such rates for the primary endpoint. Repeated events within a participant also mean that the observations are not necessarily independent. Methods for recurrent events can account for that structure, but the registry record does not report which method, if any, was used.

There is no single uncertainty interval or inferential test posted for the primary event totals. Without that analysis, the counts should not be interpreted as demonstrating a statistically supported difference between treatment schedules. The trial’s randomization is relevant to its design, but randomization does not turn raw totals into a valid comparison when exposure and repeated events are not addressed in the reported analysis.

How to read the secondary comparisons

The posted comparisons for the binary immune outcomes use risk differences. A risk difference is the difference between the proportions with an outcome in two groups; a value of zero corresponds to equal observed proportions. The listed comparison uses Arm I as the reference and contrasts it with Arm II or Extended Treatment Arm III. The risk-difference estimates and intervals are unadjusted recalculations from posted summary counts. No sponsor-reported analyses are listed for these secondary outcomes.

A confidence interval describes uncertainty around an estimated difference under the assumptions of the calculation. It is not a range containing a fixed proportion of individual participant outcomes. For Arm II, the interval extends from -0.288 to 0.442; for Extended Treatment Arm III, it extends from -0.491 to 0.076. Each includes zero, so neither calculation rules out no difference at the conventional two-sided 0.05 significance level. The intervals are broad, reflecting the limited information in the small comparison groups. The associated unadjusted p-values, 0.68 and 0.131, likewise do not provide evidence against a no-difference hypothesis at that level. These values do not establish equivalence or prove that the groups are the same.

The registry also reports relative risks and odds ratios for these comparisons. Such measures express a contrast on a different scale from the risk difference. They can be less intuitive when event counts are small, and their intervals are also broad. All these calculations use the posted summary counts; they are not a substitute for a prespecified sponsor analysis. No adjustment for baseline characteristics or other covariates is reported.

Planning illustrations are not trial power

The sample-size illustrations use the observed effect as a starting point and show hypothetical participants per arm for 80% or 90% power at different fractions of that effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. For the immune-response comparison of Arm II with Arm I, the illustrations for 100% of the observed effect are 600 participants per arm for 80% power and 802 for 90% power. For Extended Treatment Arm III compared with Arm I, the corresponding figures are 58 and 77. The displayed illustrations also consider 75% and 50% of the observed effect.

These are planning illustrations, not observed power and not the trial’s own design justification. They are especially sensitive to the observed effect in small samples: an unstable estimate can produce a planning figure that does not generalize. The registry record does not report a sample-size justification used to design the trial, and these calculations should not be presented as evidence that the completed study was adequately powered.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including PAP-specific immune response, PAP-specific T-cell response, PD-1 expression, and PD-L1 expression. It also includes more than one comparison of treatment arms for the posted binary outcomes. The registry record does not report whether a multiplicity adjustment was planned or used. Without such information, the unadjusted p-values should be understood as individual exploratory results, not as a controlled family of confirmatory tests.

Multiplicity matters because examining several outcomes or comparisons creates more opportunities for a result to appear noteworthy by chance. General statistical explanation: procedures for controlling multiplicity can change the threshold for declaring evidence or adjust uncertainty estimates. Whether such a procedure is appropriate depends on the prespecified analysis plan and which comparisons were considered primary. Those details are not reported in the registry record, so no adjusted interpretation can be reconstructed from the posted information.

Missing-data handling is also not reported in the registry record. The posted arm sizes and outcome counts do not explain whether every randomized participant contributed data to each outcome, how participants with incomplete follow-up were handled, or whether any outcomes were missing. The record does not state whether analyses used an intention-to-treat population, a per-protocol population, or another analysis set. It also does not provide outcome-specific denominators for every secondary measure beyond the posted arm counts.

These omissions limit interpretation of both the primary and secondary findings. In a trial with a stated observation period extending up to 23 months, participants may not necessarily have the same duration of observation; the registry does not provide the arm-specific follow-up details needed to assess this. The randomization method, allocation concealment, sample-size justification, interim analyses, and full statistical analysis plan are not reported in the registry record. Their absence from the record does not establish what the investigators did; it means those methods cannot be evaluated from the posted information.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thromboembolic event (15.4%), stroke (7.7%), myocardial infarction (7.7%), adrenal insufficiency (7.7%), diarrhea (7.7%).

The primary safety endpoint counts total adverse events: 117 in Arm I, 173 in Arm II, 163 in Extended Treatment Arm III, and 225 in Extended Treatment Arm IV. These totals are not counts of distinct affected participants. The separate safety summaries list participants at risk and participants affected by serious or other adverse events. Serious adverse events affected 1 of 13 participants in Arm I, 7 of 13 in Arm II, 4 of 20 in Extended Treatment Arm III, and 3 of 20 in Extended Treatment Arm IV. Other adverse events affected 12 of 13, 13 of 13, 19 of 20, and 19 of 20, respectively.

The registry also lists deaths by arm: 13, 9, 16, and 9, respectively. It does not report causes of death or whether deaths were considered related to study treatment. The serious-event terms listed include thromboembolic event (15.4%), stroke (7.7%), myocardial infarction (7.7%), adrenal insufficiency (7.7%), diarrhea (7.7%), and pancreatitis (7.7%). The record does not provide arm-specific breakdowns for these terms in the listed summary.

These safety figures are descriptive. Differences in follow-up, exposure, repeated events, and event classification can affect counts. The registry record does not provide an exposure-adjusted comparison or a sponsor-reported statistical analysis of these safety summaries.

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

The posted results describe adverse-event totals and participant counts in four treatment arms, as well as selected immune-response counts. They show that adverse events were recorded in every arm and that serious and other adverse events were reported among participants. They also show observed variation in the total event counts and in the participant counts across arms. Those patterns are observations, not proof that a particular treatment schedule caused more or fewer events.

The primary endpoint is a total count, and the registry does not provide a statistical comparison, uncertainty interval, or adjustment for exposure time. Consequently, the totals cannot establish comparative safety. The participant-level safety summaries add information about how many people were affected, but the record does not report treatment attribution, causes of death, or detailed arm-specific results for the listed serious-event terms.

The immune-response comparisons are unadjusted calculations based on small groups. Their confidence intervals include zero and are wide, so they do not precisely resolve the size or direction of a difference. These findings do not establish equivalence, a clinically meaningful immune effect, or a treatment benefit. The registry record also does not report sponsor analyses for these secondary outcomes.

More generally, a statistical result is not a treatment recommendation. The registry entries describe measurements collected in this pilot study and the limits of the available analysis. They do not establish whether the vaccine and pembrolizumab combination improves health outcomes, whether one schedule is preferable, or how the findings apply outside the studied population. Those questions would require evidence and analyses beyond the posted results.

13. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the difference between an event count and a participant-level safety measure. The primary endpoint totals how many adverse events were recorded per arm, whereas the safety summaries count participants affected by serious or other events. These quantities are related but answer distinct questions. Treating them as interchangeable can distort interpretation, particularly when individuals may experience multiple events.

The study also highlights why a randomized design does not eliminate the need for an appropriate analysis. Random allocation supports comparisons, but meaningful interpretation still depends on clearly defined outcomes, follow-up, analysis populations, and methods that account for the data structure. For an event-count endpoint, the number of events alone may not capture differing time at risk or repeated events within participants. The registry record does not report an adjusted primary comparison.

The secondary calculations demonstrate the role of uncertainty. Point estimates can suggest a direction, but wide confidence intervals show that small samples may leave a broad range of effects compatible with the observations. An unadjusted p-value does not communicate the size or precision of an effect, and it does not answer whether a result is clinically important. The planning illustrations also show why effect assumptions matter: a sample-size calculation based on an observed effect is a planning exercise, not a measure of the completed trial’s power.

Finally, the record distinguishes what can be described from what cannot be established. It posts several outcomes and safety counts, but does not report a complete analysis plan, missing-data approach, or multiplicity handling. Careful interpretation preserves the descriptive value of the results without claiming more certainty than the registry record supports.

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.

Several limitations specific to this record affect interpretation. The primary endpoint is reported as a total event count per arm, without an exposure-adjusted rate or a sponsor-reported comparison. The registry gives a broad timeframe but not arm-specific time at risk, so differences in treatment duration or follow-up cannot be assessed from the posted information. The totals also do not indicate how events were distributed across participants.

The study is described as a pilot and the arm sizes are limited. This constrains the precision of comparisons, especially for outcomes with relatively few participants experiencing the outcome. The unadjusted immune-response calculations have wide confidence intervals. They should not be treated as confirmatory evidence or as a substitute for a prespecified analysis.

The record does not report the randomization method, allocation concealment, analysis populations, missing-data methods, multiplicity handling, interim analyses, or a full statistical analysis plan. It also does not report results for all named secondary outcomes. The reported death counts have no accompanying causes or treatment attribution, and the listed serious adverse-event terms are not broken down by arm in the summary.

There are four treatment schedules, including extended treatment schedules that differ in timing and maximum number of doses. This makes a simple pooled interpretation inappropriate without a stated analysis strategy. The record’s posted counts do not explain how the extended arms relate analytically to the initial arms. The sponsor analyses for the posted secondary outcomes are not listed in the registry record, so the available comparisons are unadjusted recalculations from summary counts rather than reported trial analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer — NCT02499835.
• Registry record last updated 2023-08-01; status last verified 2023-07.
• Results first posted 2022-12-01.
• 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.

18. Record Summary

The registry record describes a completed, randomized, parallel-group Phase 1 and Phase 2 pilot trial of pTVG-HP DNA vaccine and pembrolizumab in patients with castration-resistant, metastatic prostate cancer. Masking was none, and enrollment was 66. The four arms varied the timing and schedule of vaccination and pembrolizumab.

The primary endpoint was adverse-event incidence using National Cancer Common Terminology Criteria, Version 4, with total events calculated per arm over a timeframe of up to 23 months. The posted event totals were 117, 173, 163, and 225 across Arms I, II, III, and IV. Participant counts for serious and other adverse events and selected immune-response outcomes are also listed. The registry record does not report sponsor analyses for the posted secondary outcomes or a statistical comparison for the primary event totals.