NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine (NCT00199849), a non-randomized phase 1 study. The primary outcome is Number of Patients With Dose Limiting Toxicities (DLTs) and Number of Patients With Adverse Events.

2. Clinical Question

3. Trial Design

This was a completed phase 1 study sponsored by the Ludwig Institute for Cancer Research. The registry lists an enrollment of 18 and a non-randomized, sequential design with no masking. The recorded start date is 2004-09-27 and the primary completion date is 2006-09-11. The study evaluated NY-ESO-1 plasmid DNA cancer vaccine, given by particle-mediated epidermal delivery to patients with tumor types known to express NY-ESO-1 or LAGE-1.

The descriptions identify three cohorts: Cohort 1 received 4 µg, while Cohorts 2 and 3 received 8 µg. The available descriptions do not establish why there were separate cohorts at the same stated dose, nor do they fully specify the schedule or any other differences between cohorts. Such details are not reported in the registry record. The record describes delivery at 500 psi using the XR-1 Powderject device.

Because allocation was not randomized and there was no masking, the study is primarily suited to descriptive assessment of safety and immune outcomes within the enrolled groups. It is not a randomized dose comparison. Sequential enrollment also means that cohort membership may be associated with timing or other differences; the registry record does not report enough detail to assess those possibilities. A formal sample-size justification, planned interim analyses, and the statistical analysis plan are not reported in the registry record.

The registry lists the primary outcome as the number of participants with dose-limiting toxicities and adverse events, assessed up to 13 weeks. It also lists tumor response under RECIST, antibody titer increases, NY-ESO-1-specific CD4+ and CD8+ T-cell increases, and delayed-type hypersensitivity skin reactions as secondary outcomes. The registry record reports no analyses. It does not give counts for the primary endpoint itself or the listed secondary outcomes in the information recorded for this analysis.

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:

Analysis population for the primary outcome, as defined in the registry: All patients who received at least one dose of NY-ESO-1 Plasmid DNA Vaccine.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: All patients who received at least one dose of NY-ESO-1 Plasmid DNA Vaccine.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients With Dose Limiting Toxicities (DLTs) and Number of Patients With Adverse Events, measured over up to 13 weeks.

The primary endpoint is a count-based safety outcome: the number of participants with dose-limiting toxicities (DLTs) and the number with adverse events. The stated assessment period is up to 13 weeks. The primary outcome population is patients who received at least one dose of NY-ESO-1 plasmid DNA vaccine.

Adverse events were to be graded using the National Cancer Institute Common Toxicity Criteria, Version 3.0. The registry defines DLTs to include autoimmune phenomena at grade 2 or higher, asymptomatic bronchospasm or generalized urticaria, and hematological toxicities at grade 3 or higher. A further criterion for non-hematological toxicities is worded incompletely in the registry record, so its grade threshold cannot be established from that description. A qualifying dose-limiting adverse event also had to be considered definitely, probably, or possibly related to the investigational agent and occur between the first dose and 4 weeks after the last dose.

Using counts is useful in an early-phase safety assessment because it makes the observed number of affected participants visible, alongside the number at risk in each group. A count does not, on its own, show severity, timing, duration, or causal attribution. Nor should a general adverse-event count be treated as equivalent to a DLT count: DLT classification has additional criteria. The registry record does not report the primary endpoint’s DLT counts, so the listed adverse-event counts cannot substitute for them.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count-based endpoint convey?

In general, a count endpoint records how many participants meet a specified event definition. Its interpretation depends on the definition, observation period, and population being counted. A count is most informative when read with the corresponding number at risk, because the same count can have a different meaning in groups of different sizes. In this study, the registry lists group-specific numbers at risk for adverse events, but it does not report the primary DLT counts. The adverse-event counts should therefore remain distinct from the primary endpoint as defined.

In general, a proportion expresses the affected count relative to a stated denominator. It can help compare event frequency across groups, but it does not remove design limitations or uncertainty. No new proportions should be inferred from the listed counts when they are not reported as results. In particular, the term percentages for serious adverse events should be read with caution because their denominator and cohort attribution are not reported in the registry record.

Why does the design matter for comparisons?

In general, random allocation helps balance known and unknown participant characteristics across treatment groups, on average. This study was non-randomized and sequential, so that protection does not apply. The cohorts may differ in ways that are not captured in the recorded results. Even if event counts differ, the difference cannot be attributed to dose alone without assumptions that the registry record does not establish.

In general, masking can reduce the influence of expectations on some assessments and reporting. The registry lists no masking. This is relevant when outcomes involve clinical judgment, event attribution, or assessments that could be influenced by awareness of treatment. The record does not describe procedures intended to address such influences, so no additional safeguards should be assumed.

What is uncertainty around an estimate?

In general, a confidence interval gives a range of values compatible with the data and a specified statistical method. A narrow interval indicates greater precision than a wide interval, while a wide interval indicates substantial uncertainty. Intervals are especially useful alongside event counts because a count alone does not show how uncertain an estimated event rate may be. The registry record does not report confidence intervals for the safety results.

In general, p-values assess compatibility between data and a statistical model under a null hypothesis; they do not measure the probability that a treatment works, nor do they establish causation. A p-value is not reported for these cohort safety figures. The registry record lists zero analyses, so inferential tests or adjusted estimates should not be attributed to the record.

What does over-dispersion mean for count data?

In general, over-dispersion occurs when count outcomes vary more than a statistical model expects. If it is ignored, standard errors can be too small and intervals or tests can appear more certain than warranted. A suitable count model may account for extra variation, but choosing one requires information about the outcome distribution, design, and analysis plan. No such model or plan is reported in the registry record. The group counts are therefore best treated as descriptive.

How should planning illustrations be read?

In general, a sample-size calculation asks how many participants might be needed under stated assumptions to detect an effect with a chosen statistical procedure. The record’s planning assumptions specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. These are planning assumptions, not evidence that the study had a particular probability of detecting an effect. Sample-size illustrations are not observed power and do not change the actual non-randomized design.

The registry record does not report a formal sample-size justification for the trial, its assumed target effect, or a statistical analysis plan. It also does not report an effect estimate for the primary DLT endpoint from which to assess precision. For this reason, planning calculations should not be interpreted as proof that the study was adequately powered to answer a safety or efficacy question. A completed study can still leave substantial uncertainty when the endpoint estimates and analyses are not reported.

Why are endpoint definitions and time windows important?

In general, an endpoint definition determines which events count, while the observation window determines when they must occur. Here, DLTs require a specified type or grade of event, a judged relationship to the investigational agent, and occurrence between the first dose and 4 weeks after the last dose. The primary endpoint timeframe is given as up to 13 weeks. Those descriptions do not make every adverse event a DLT. The incompletely worded non-hematological toxicity criterion further limits exact interpretation of the DLT definition as recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes: RECIST tumor response, NY-ESO-1-specific humoral immunity based on antibody titer increase, NY-ESO-1-specific cellular immunity based on CD4+ and CD8+ T-cell increases, and delayed-type hypersensitivity skin reactions. The primary outcome includes counts of participants with DLTs and adverse events. Considering multiple outcomes raises a general multiplicity issue: when many outcomes are tested, the chance of at least one apparently unusual result can increase. Statistical approaches can address that issue, but the registry record does not report a multiplicity strategy, prespecified hierarchy, or adjustment.

The registry record lists zero analyses and does not report results for the primary DLT count or the listed secondary outcomes. It also does not report p-values or confidence intervals for these outcomes. Consequently, it is not possible to determine from the record whether every planned outcome was analyzed, whether outcomes were selected for reporting, or how uncertainty was handled.

The primary population is described as all patients who received at least one dose. That identifies an exposed population, but the registry record does not describe how missing measurements, discontinuations, or unevaluable participants were handled for each outcome. It does not report an analysis-population rule for the immune or tumor-response outcomes. Missing-data methods, reasons for missingness, and sensitivity analyses are not reported in the registry record. Results should not be treated as complete follow-up for every participant merely because the study is marked completed.

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: pyrexia (33.3%), bladder obstruction (14.3%), hemorrhage urinary tract (14.3%), dysphagia (14.3%).

The serious adverse-event counts are reported by cohort: one affected participant among 3 at risk in Cohort 1, one among 7 in Cohort 2, and one among 7 in Cohort 3. The record lists no deaths in each cohort. Other adverse events are recorded for 3 participants among 3 at risk in Cohort 1 and 7 among 7 at risk in each of Cohorts 2 and 3. These figures describe the entries in the adverse-event record; they do not establish causation.

The listed serious-event terms and percentages are pyrexia, 33.3%; bladder obstruction, 14.3%; hemorrhage urinary tract, 14.3%; and dysphagia, 14.3%. The term percentages have no reported denominator or cohort attribution in the registry record, and terms may not represent separate people. They should not be combined or interpreted as mutually exclusive categories.

Serious adverse events, all adverse events, and DLTs are not interchangeable. DLT classification depends on the stated toxicity criteria, timing, and relationship to the investigational agent. Although the registry defines DLTs, it does not report their counts. The safety figures therefore provide a limited descriptive account, not a complete result for the primary endpoint.

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

The record establishes that this completed phase 1 study evaluated a plasmid DNA cancer vaccine delivered by particle-mediated epidermal delivery in a non-randomized, sequential design. It documents adverse-event counts by cohort, including serious adverse events and other adverse events, and lists no deaths in the cohorts. These entries describe what was recorded; they do not by themselves establish whether an event was caused by the vaccine.

The record does not report the primary DLT counts, despite defining DLTs as a primary outcome. Nor does it report results for the listed tumor-response or immune outcomes. Therefore, the available information does not support a conclusion about those outcomes. The recorded adverse-event counts cannot stand in for the missing DLT, response, or immunogenicity results.

The cohort counts also do not establish a dose-response relationship. Cohort 1 is described at 4 µg and Cohorts 2 and 3 at 8 µg, but allocation was not randomized and the cohorts are not a controlled comparison. Differences in participant characteristics, timing, or other unreported features could contribute to differences in observed events. The registry record does not provide analyses that address these possibilities.

In general, an absence of reported statistical evidence is not evidence that an effect is absent. Here, the record lists no analyses and supplies no confidence intervals for the key outcomes. The size and precision of any effect cannot be judged from the posted counts alone. Likewise, the study’s completed status is a registry status, not a statement that every endpoint result is available.

The defensible interpretation is therefore narrow: the registry records cohort-level safety counts and selected serious-event terms, while important details of the primary endpoint and secondary outcomes are not reported in the registry record. Any broader statement about comparative safety, tumor response, or immune response would go beyond these recorded results.

13. Why This Trial Matters Statistically

This study illustrates why early-phase trial results need to be interpreted through both endpoint definitions and design. A count of adverse events is easy to understand, but it answers only the question defined by that count. The primary endpoint distinguishes DLTs from general adverse events through toxicity criteria, timing, and an assessment of relation to the investigational agent. Without the DLT results, the safety question stated as primary remains incompletely answered in the registry record.

The non-randomized, sequential design also matters statistically. Cohort counts can document what happened among participants in each group, but they do not provide the protection against confounding that random allocation can offer. The two stated dose levels do not by themselves create a reliable dose comparison. The reported count differences, if any, cannot be interpreted as dose effects without accounting for group comparability and uncertainty.

The record also demonstrates the difference between study completion and result completeness. A trial can be marked completed while the registry record lacks analyses, endpoint estimates, or uncertainty measures. Secondary outcomes may be clinically or scientifically relevant, but listing an outcome does not mean its result is available. Clear reporting of denominators, outcome definitions, missingness, and estimates is essential for readers to assess what the data can support.

For biostatisticians and clinical researchers, the central lesson is to separate descriptive safety reporting from inferential claims. Counts should be paired with their denominators and event definitions, while comparisons should reflect the allocation design and precision of the estimates. When key outcomes and analyses are absent, acknowledging those gaps is more informative than drawing conclusions from isolated counts.

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 central limitation is that the registry record does not report the primary DLT counts, although DLTs are included in the primary endpoint. The available adverse-event counts do not resolve that gap because general adverse events and DLTs have different definitions. The registry also does not report results for its listed tumor-response and immune outcomes, so those questions remain unanswered in the recorded results.

Interpretation of the safety data is constrained by the non-randomized, sequential allocation and absence of masking. The cohorts are not a randomized control comparison, and the record does not report details sufficient to assess cohort comparability or possible changes over time. No adjusted analysis is reported. The listed group counts should therefore be treated descriptively.

The DLT definition includes an incompletely specified non-hematological toxicity threshold. That wording prevents a full reconstruction of the classification rule from the registry record. In addition, serious-event term percentages are listed without their denominator or cohort attribution in the available information. The terms cannot be assumed to represent mutually exclusive events or participants.

Further limitations include the absence of reported confidence intervals, p-values, analysis populations for secondary outcomes, missing-data methods, and multiplicity procedures. A formal sample-size justification and statistical analysis plan are not reported in the registry record. These omissions limit assessment of precision, completeness, and how outcome analyses were planned. They do not imply that the study did not collect or analyze the information; they mean that it is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine — NCT00199849.
• Registry record last updated 2022-10-10; status last verified 2022-10.
• Results first posted 2021-10-08.
• 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

This completed phase 1 study evaluated NY-ESO-1 plasmid DNA cancer vaccine delivered by particle-mediated epidermal delivery in patients with tumor types known to express NY-ESO-1 or LAGE-1. It was non-randomized, sequential, and unmasked. The registry lists an enrollment of 18, with a 4 µg dose in Cohort 1 and an 8 µg dose in Cohorts 2 and 3.

The primary outcome was the number of participants with DLTs and adverse events, assessed up to 13 weeks. The adverse-event record lists one participant with a serious adverse event in each cohort, other adverse events in the recorded at-risk participants, and no deaths in each cohort. The registry record does not report the primary DLT counts or results for the listed secondary outcomes. It also lists zero analyses. The available counts are descriptive and do not establish a causal or comparative treatment effect.