A Pilot Study of NY-ESO-1b Peptide Plus CpG 7909 and Montanide® ISA-51 in Patients With Cancer.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Study of NY-ESO-1b Peptide Plus CpG 7909 and Montanide® ISA-51 in Patients With Cancer. (NCT00199836), a na phase 1 study. The primary outcome is Number of Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline..

2. Clinical Question

3. Trial Design

This was a Phase 1, completed, single-group study sponsored by the Ludwig Institute for Cancer Research. The registry lists enrollment of 14 and describes patients with cancer expressing NY-ESO-1 or LAGE-1 antigen as the study group. The record lists no masking and allocation as not applicable. It therefore does not describe a randomized treatment comparison, and there is no separate control arm against which to interpret outcomes.

The intervention was a combination of NY-ESO-1b peptide, CpG 7909, and Montanide® ISA-51. The arm description specifies 100 μg of peptide, 1 mg of CpG 7909, and 0.5mL of Montanide® ISA-51, given by subcutaneous injection. Injections began on week 1 and were repeated every three weeks for 4 injections total. The arm description is incomplete after its reference to a three-week interval, so further details of the schedule are not reported in the registry record.

The study began on 2003-09-03, had a primary completion date of 2005-09-05, and is listed as completed. The primary endpoint timeframe was up to 27 weeks. Blood-sample collection for antibody assessment was described at baseline, before the second, third, and fourth injections, and after the fourth injection in both cycles 1 and 2.

The named secondary outcome was the number of patients with tumor responses measured by RECIST. The registry lists 5 outcome measures, but does not report the other outcome titles in the available record. The registry record does not describe a separate control group, masking procedure, or a 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.

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-1b peptide, 100 μg mixed with 1 mg CpG 7909 and 0.5mL of Montanide® ISA-51 and had pre- and post-treatment samples taken.

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 Patients With NY-ESO-1 Specific Humoral Immunity as Determined by an Increase in Antibody Titer From Baseline., measured over up to 27 weeks.

The primary endpoint was a participant count for NY-ESO-1-specific humoral immunity. Its title defines the event as an increase in antibody titer from baseline. Antibodies were assessed in blood samples using an enzyme-linked immunosorbent assay, with samples described at baseline and at specified points during treatment and follow-up through the stated timeframe of up to 27 weeks.

An antibody endpoint is a measure of an immune response, rather than a direct measure of tumor shrinkage or survival. A count of participants meeting a response definition can indicate how many in the endpoint population met that definition. It does not, by itself, establish that the intervention caused the response or that the response corresponded to a clinical benefit.

The registry record defines a positive response as a readable optical density at 280 nm. That wording does not specify a quantitative cutoff for the stated increase in antibody titer from baseline. The relationship between the title’s increase-from-baseline criterion and the description’s readable-optical-density criterion is therefore unclear in the registry record. The endpoint result, including the number meeting the response definition, is not reported in the registry record. The number of participants with the required pre- and post-treatment samples is also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a count endpoint: the number of participants meeting a binary response definition. In general, a binary endpoint classifies each participant as meeting or not meeting a criterion, and the count records how many meet it. The count is meaningful only alongside a clearly defined analysis population and a consistent rule for classifying results. In this study, the endpoint population required at least one dose and pre- and post-treatment samples. The registry record does not report the number meeting those requirements or the number classified as responders.

What does a confidence interval convey?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified analysis. For a response proportion, it helps show how compatible the observed data are with a range of underlying response rates. A narrow interval indicates greater precision than a wide interval, while neither interval alone establishes causality. The registry record does not report a confidence interval for the primary endpoint, and no interval can be interpreted without the result and analysis population.

Why does the endpoint definition matter?

Measurement rules determine which observations count as events. Here, the endpoint title refers to an increase in antibody titer from baseline, while the description says that a positive response was a readable optical density at 280 nm. These statements leave important operational details unclear: the threshold for an increase, the handling of unreadable samples, and the way repeated samples were used to classify a participant. Without those details, readers cannot fully reproduce the response classification or assess whether it was applied consistently.

Repeated sample collection also raises a distinction between measurement occasions and participants. The endpoint is a participant count, not a count of samples. In general, repeated measurements can help characterize change over time, but a participant-level response rule is needed to combine measurements into a single classification. The registry record describes collection occasions in cycles 1 and 2 but does not report the rule for combining those observations into the primary endpoint.

What can a single-group design estimate?

A single-group study can describe outcomes among people who received the intervention. In general, it cannot provide the same treatment-effect contrast as a randomized controlled design, because it lacks a concurrent comparison group. The observed outcome may reflect the intervention, participant characteristics, natural variation, or other influences. This is a design limitation, not a computational issue that can be corrected by a confidence interval or a more elaborate model.

For a binary count, an analysis might report the number meeting the event definition and the corresponding proportion in a defined population. More complex methods may be appropriate when observations are clustered, repeated, or otherwise dependent. Over-dispersion is a general concern when a model assumes less variability than the data contain; it can make standard errors too small and uncertainty appear overstated in precision. The registry record does not describe a model, an over-dispersion assessment, or any inferential analysis for this endpoint.

How should p-values and multiplicity be understood?

In general, a p-value measures how inconsistent data are with a specified null hypothesis under the assumptions of the chosen statistical test. It is not the probability that the null hypothesis is true, and it does not measure clinical importance. The registry record reports no analysis entries, p-values, or statistical test for the primary endpoint. A p-value therefore cannot be used to interpret this study’s primary result from the registry record.

When a study evaluates multiple outcomes or analyses, the chance of at least one apparently unusual result can increase if each is tested separately. This is the general issue of multiplicity. A prespecified hierarchy or an adjustment method can address some multiplicity concerns, but the registry record does not report a multiplicity strategy. The record lists 5 outcome measures and names tumor response as a secondary outcome; it does not provide a complete analysis plan.

What do planning illustrations mean?

In general, a sample-size calculation depends on design assumptions, including the target effect, significance level, allocation, and statistical method. The stated planning assumptions describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The record also distinguishes participant counts per arm from total event counts for time-to-event designs. These are planning assumptions, not evidence from this single-group study, and a planning illustration is not observed power. The registry record does not report the trial’s own sample-size justification.

Statistical precision depends on both the number of observations and the amount of variability, as well as the endpoint definition and design. The enrollment figure alone does not establish how many participants had evaluable samples or how precise an antibody-response estimate would be. Since the primary response count and its analysis population are not reported in the registry record, its precision cannot be assessed from the posted information.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures and names one secondary outcome: tumor responses measured by RECIST. The primary outcome concerns NY-ESO-1-specific humoral immunity. The registry record does not report a statistical analysis plan, a hierarchy for testing outcomes, or a method for controlling multiplicity. Without that information, it is not possible to determine whether any inferential claims were intended to be confirmatory or exploratory. The record also lists no analysis entries.

The endpoint population was defined as participants who received at least one dose and had pre- and post-treatment samples. This definition means the primary analysis depends on the availability of paired samples, but the number meeting the definition is not reported in the registry record. The record does not describe how missing samples, unreadable assay results, withdrawals, or other incomplete observations were handled. It also does not report whether participants without paired samples were included in any alternative analysis.

These gaps matter because the endpoint is based on a change from baseline. If sample availability or assay readability differs across participants, the analyzed group could differ from the enrolled group. That is a general concern about missing data, not evidence that such a difference occurred in this study. The registry record does not provide enough information to assess its direction or magnitude.

The stated endpoint population and the registered enrollment should therefore be kept distinct. Enrollment is 14; the number in the primary endpoint analysis population and the number with a positive response are not reported in the registry record. No imputation method or sensitivity analysis for missing data is reported in the registry record.

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: angina pectoris (7.1%), asthenia (7.1%), brain metastases (7.1%), cholecystitis (7.1%), pancreatitis (7.1%).

The registry lists safety counts for the group of patients with cancer expressing NY-ESO-1 or LAGE-1 antigen. It reports 14 participants at risk for serious adverse events and 6 affected by serious adverse events. For other adverse events, it lists 14 at risk and 14 affected. The record also lists 2 deaths. These are descriptive entries; the registry does not state that the deaths or adverse events were caused by the intervention.

The serious adverse-event terms listed among the most frequent are angina pectoris, asthenia, brain metastases, cholecystitis, pancreatitis, and convulsion. Each term is reported at 7.1%. The record does not give participant-level details, timing, duration, severity gradations beyond the serious-event classification, or an attribution assessment for these terms. It also does not clarify whether the same participant could be represented by more than one term, so the term frequencies should not be added or treated as separate people.

At-risk counts describe the group used for the event listing; affected counts describe participants recorded with an event category. Neither count alone establishes a causal relationship. The registry record does not provide a comparator group for assessing whether event frequency differed from another treatment or from an untreated group.

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

The record establishes that this was a completed Phase 1, single-group study of a combination containing NY-ESO-1b peptide, CpG 7909, and Montanide® ISA-51 in patients with cancer expressing NY-ESO-1 or LAGE-1. It describes an antibody-immunity endpoint and lists a secondary tumor-response outcome. It also records adverse-event counts and deaths. These registry entries describe the study and the information entered in the registry; they do not, on their own, establish a treatment effect.

The primary endpoint result is not reported in the registry record. Therefore, the record does not show how many participants met the antibody-response definition, what proportion that represented in the endpoint population, or how uncertain an estimate would be. The wording of the endpoint also leaves the response threshold unclear: the title refers to an increase in antibody titer from baseline, while the description refers to a readable optical density at 280 nm. That ambiguity limits interpretation even if a count were available.

The single-group design also limits what can be inferred. An outcome observed after treatment would not provide a direct contrast with an untreated group or another regimen. Without a comparator, the study cannot separate an intervention-associated pattern from other explanations. The registry’s record of adverse events is likewise descriptive and does not determine causation.

The secondary tumor-response result is not reported in the registry record. The listed safety counts should be interpreted as recorded counts in the study group, not as a comparison or proof that the intervention caused an event. The record does not provide enough information to quantify a comparative benefit or harm.

Planning estimates based on an observed effect, if considered, answer a different question: they illustrate possible design requirements under stated assumptions. They are not a substitute for an observed endpoint result and are not observed power. In short, the registry record supports a careful account of the study’s design, measures, and recorded safety information, but does not report the primary or secondary efficacy results needed to quantify response.

13. Why This Trial Matters Statistically

Statistically, the study illustrates why design and outcome definition are central to interpreting a clinical result. A participant count can look straightforward, but its meaning depends on who was eligible for the analysis and what rule classified a response. Here, the registry defines the primary population by receipt of at least one dose and availability of pre- and post-treatment samples, while the number meeting that definition is not reported. The response wording also leaves uncertainty about the threshold connecting a change in antibody titer with a readable assay signal.

The single-group structure is important as well. It allows outcomes to be described among treated participants, but it does not supply a concurrent control comparison. That means an observed response count, if reported, would not alone identify the effect attributable to the combination. Statistical uncertainty measures can describe precision, but cannot replace the missing design contrast.

The record also shows why safety counts require context. Counts of participants with serious and other adverse events provide descriptive information, while causality, timing, overlap between event terms, and comparative risk require additional detail. The listed serious-event terms do not function as independent participant counts when overlap is not clarified.

Finally, the registry record distinguishes the study’s observed information from planning assumptions. Sample-size illustrations can help frame future designs, but they rely on assumptions and are not evidence that the current study had a particular level of power. The primary outcome result and its uncertainty are not reported in the registry record, so those planning concepts cannot be used to infer the missing finding. The statistical lesson is to keep design, endpoint definition, analysis population, observed results, and planning scenarios separate.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record has important limitations for interpreting this study’s results. Most directly, it does not report the primary antibody-immunity count or the secondary tumor-response result. It lists 5 outcome measures but does not provide all outcome descriptions in the available record. No analysis entries are listed, and the statistical analysis plan is not reported in the registry record.

The primary endpoint has an unresolved definition issue. Its title describes an increase in antibody titer from baseline, while the endpoint description calls a readable optical density at 280 nm a positive response. The record does not state the quantitative increase required, how repeated samples were combined, or how unreadable samples were treated. The number of participants meeting the endpoint-specific sample criteria is also not reported.

The study was single-group, with no separate control arm described. This limits causal interpretation and means the record does not provide a like-for-like treatment comparison. The registry lists no masking. Details of the injection schedule are incomplete after the arm description begins to describe a three-week interval, so the remaining schedule is not reported in the registry record.

For safety, the record provides group-level counts and selected serious-event terms but does not report participant-level timing, event duration, attribution, or whether terms overlap within participants. The two deaths are listed without causal information. These limitations mean the counts should be treated as registry-record descriptions, not as comparative estimates or evidence of causation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Pilot Study of NY-ESO-1b Peptide Plus CpG 7909 and Montanide® ISA-51 in Patients With Cancer. — NCT00199836.
• Registry record last updated 2022-10-10; status last verified 2022-10.
• Results first posted 2021-07-15.
• 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 enrolled 14 patients with cancer expressing NY-ESO-1 or LAGE-1 antigen and used a single-group design with no masking. The intervention combined NY-ESO-1b peptide, CpG 7909, and Montanide® ISA-51. Injections were described as subcutaneous, beginning on week 1 and repeated every three weeks for 4 injections total.

The primary endpoint concerned the number of participants with NY-ESO-1-specific humoral immunity, with a timeframe of up to 27 weeks. Its result is not reported in the registry record. The record also names tumor response measured by RECIST as a secondary outcome, but its result is not reported in the registry record. Safety entries include 6 participants with serious adverse events, 14 with other adverse events, and 2 deaths; the record does not establish causation. The registry does not report the statistical analysis plan, missing-data handling, or the primary endpoint analysis population size.