ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer (NCT02002182), a non-randomized phase 2 study. The primary outcome is HPV-Specific T Cell Response Rate.

2. Clinical Question

The trial was designed as a window-of-opportunity study: vaccination was given before planned surgery, with the primary measure focused on an immune response at surgery. The question is therefore about a measured biological response in the participants with available surgery-time measurements. It is not a randomized comparison of clinical outcomes between vaccination and standard care, and the registry does not report a comparative treatment-effect estimate for the primary endpoint.

3. Trial Design

This was a Phase 2, parallel-group, non-randomized trial with no masking. The registry lists enrollment of 15 and status as completed. The study start is recorded as 2013-12, and primary completion as 2018-07-01. Its title describes vaccination before robot-assisted resection of HPV-positive oropharyngeal squamous cell carcinoma.

The treatment-vaccine group received ADXS11-001 (ADXS-HPV). The registry describes two intravenous vaccinations at a dose of 1x10^9 cfu, administered as a 500ml infusion over 60 minutes. The comparator was an observational control group receiving standard-of-care therapy only. The record explicitly notes that the control group was optional for the surgery-time T-cell measurement and that such measurements were not collected for that group.

Because allocation was not randomized, the groups should not be treated as if they were exchangeable by design. Differences in participant characteristics, care, or availability of measurements could influence comparisons. The record does not report a randomization procedure, masking, or a statistical adjustment plan that would address such differences. It also does not report the rationale for the enrollment target, participant flow by reason for inclusion or exclusion, or a detailed schedule of assessments beyond the primary endpoint’s time at surgery.

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: The analysis included participants who had HPV-specific T cell response measurement at time of surgery. T cell response data were not collected at time of surgery for the control group, which was an optional observational group.

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 HPV-Specific T Cell Response Rate, measured over At time of surgery.

The primary endpoint is the HPV-specific T-cell response rate at the time of surgery. It is defined as the proportion of participants with a >2-fold increase in HPV-specific T-cell response from baseline to surgery. The endpoint converts an immune measurement into a binary classification: each participant with the required increase meets the response definition, while others do not.

A proportion is used to describe how common the defined response was in the endpoint analysis population. The registry specifies a 95% confidence interval as the measure of dispersion. As a general statistical explanation, a confidence interval communicates uncertainty around an estimated response rate; it is not a guarantee that the true value lies within the interval. Its interpretation depends on the analysis and the assumptions used to construct it.

The analysis population was limited to participants who had an HPV-specific T-cell response measurement at surgery. The control group did not contribute surgery-time T-cell measurements because it was an optional observational group. Therefore, the endpoint as described is not a complete comparison of response rates between the vaccine and control groups. The registry record does not report the observed response proportion, confidence interval, or the underlying response counts.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record names a binary proportion as the primary endpoint and a 95% confidence interval as its dispersion measure. It does not provide endpoint result values or a detailed statistical analysis plan. The explanations below describe general statistical concepts and distinguish them from methods explicitly documented in the record.

What does the response rate represent?

As a general statistical explanation, a response rate is the number of participants meeting a defined response criterion relative to the participants included in that endpoint analysis. In this trial, the criterion is a >2-fold increase in HPV-specific T-cell response from baseline to the time of surgery. The measure summarizes how often the defined response was observed in the analysis population. It does not, on its own, establish why a response occurred or whether it leads to a clinical benefit.

The registry says that the primary analysis included participants with an HPV-specific T-cell response measurement at surgery. This means the available-measurement population, rather than necessarily every enrolled participant, is relevant to the endpoint. The number with an observed measurement and the number meeting the response definition are not reported in the registry record.

How should a confidence interval be read?

As a general statistical explanation, a confidence interval gives a range of values compatible with an estimate under the method’s assumptions. A narrower interval indicates greater statistical precision than a wider interval, while the interval’s location describes the range of response rates compatible with the data and method. It does not address all sources of uncertainty, such as selection into the analysis population or differences between non-randomized groups.

The registry specifies a 95% confidence interval for the primary endpoint, but does not report its endpoints or the method used to calculate it. It is therefore not possible to assess the reported estimate’s precision or verify the calculation from the registry record.

What does the design imply for comparison?

The trial is recorded as parallel and non-randomized, with no masking. As a general statistical explanation, random allocation can help balance measured and unmeasured characteristics between groups, while non-random allocation does not provide that protection. An observed difference between non-randomized groups can reflect treatment, differences in who entered each group, differences in care, or other factors. Statistical adjustment may address measured differences under stated assumptions, but the registry record does not report an adjustment plan or comparative primary-endpoint analysis.

For this endpoint, the limitation is more direct: the optional observational control group did not have T-cell response data collected at surgery. Consequently, the record describes a response-rate endpoint in the participants with measurements, rather than a measured vaccine-versus-control contrast for that outcome.

What do the planning assumptions mean?

The record describes sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. These are planning assumptions for illustrations, not a description of the trial’s own design justification. The registry does not report the original sample-size justification or the statistical plan used to conduct the trial.

As a general statistical explanation, sample-size planning asks how much information a future study might need to detect an effect under specified assumptions. Such an illustration is not observed power and does not establish that the completed study had adequate precision. The registry record does not report an observed primary result from which readers could assess the effect or its uncertainty.

Why does over-dispersion matter for some outcomes?

As a general statistical explanation, over-dispersion occurs when observed variability is greater than a model assumes. It can make uncertainty estimates too small if the model does not allow for the extra variability. This concept can be relevant to some count or clustered outcomes, but the registry record does not report an over-dispersion assessment or describe a model for the primary binary endpoint. No specific claim about over-dispersion in this trial can be made from the record.

Overall, the registry gives the endpoint definition, measurement time, analysis-population description, and confidence-interval type. It does not report the endpoint estimate, interval limits, test result, detailed model, handling of incomplete measurements, or analysis code or protocol details. Those absences prevent a fuller assessment of the statistical result.

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("Treatment-Vaccine Group")
n      <- c(9)
events <- c(0)
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  Treatment-Vaccine Group  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the HPV-specific T-cell response rate as the primary outcome and identifies HPV-Specific T Cell Response Rate as a secondary outcome as well. It also reports three outcome measures, but does not identify all of them in the information available for this analysis. The record does not report a multiplicity strategy, such as an adjustment for testing multiple outcomes or a hierarchy for interpreting them. It is therefore not possible to determine whether or how the reported analyses accounted for multiple comparisons.

The primary analysis population was defined by availability of an HPV-specific T-cell response measurement at surgery. The record says that this measurement was not collected in the optional observational control group. It does not give a missing-data method, state how unavailable baseline measurements were handled, or report sensitivity analyses for missing measurements. The reason an individual measurement might be unavailable is not reported in the registry record.

The record lists no analyses and does not report primary endpoint counts or estimates. It therefore does not allow assessment of the extent of missing outcome data within the treatment-vaccine group, or the impact of missingness on an estimated response rate. The absence of a surgery-time measure in the control group should not be interpreted as a measured non-response; those data were not collected for that group.

The registry does not report a detailed analysis population definition beyond requiring surgery-time measurements, nor does it provide participant-flow information linking enrollment to each outcome analysis. Details about protocol deviations, exclusions, imputation, and the handling of incomplete data are not reported in the registry record.

12. 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: mouth pain (16.7%), mucositis (16.7%), hypertension (11.1%), dysphagia (11.1%), vomitting (11.1%).

The safety record reports serious adverse events for the treatment-vaccine group as 5 affected among 9 at risk, and for the control group as 1 affected among 6 at risk. It also reports deaths as 1 in the treatment-vaccine group and 0 in the control group. These are descriptive figures in the registry record; they should not be read as a causal comparison between groups.

The record lists the following top serious adverse-event terms with percentages: Mouth pain, 16.7%; mucositis, 16.7%; Hypertension, 11.1%; Dysphagia, 11.1%; Vomitting, 11.1%; and Failure to thrive, 11.1%. The information does not establish whether these events were attributed to vaccination, cancer, surgery, or another cause. The registry record does not report further details about timing, severity grading, recurrence, or event-level overlap.

The groups were non-randomized, and the record identifies the control group as observational. Differences in group composition or observation may affect comparisons. The safety figures are useful as counts reported for each group, but they do not establish that one group had greater or lesser risk because of treatment.

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

The registry describes a trial asking whether ADXS11-001 given before surgery was associated with a defined HPV-specific T-cell response at the time of surgery. It specifies the response threshold, the endpoint time, the 95% confidence interval type, and the population included in the primary analysis. These features clarify what the study intended to measure.

The record does not report the primary endpoint result. Without the response count, estimated rate, and confidence interval, the result’s magnitude and statistical precision cannot be assessed. The registry also lists no analyses, so there is no reported statistical test or treatment-effect estimate to interpret. An outcome definition is not itself evidence that the response occurred at a particular rate.

The study’s non-randomized design limits causal interpretation of group differences. In addition, the observational control group did not have surgery-time T-cell response data collected. The primary endpoint information therefore does not establish a comparative response rate between vaccination and standard care. It also does not establish an effect on cancer outcomes, survival, or the need for subsequent treatment; those results are not reported in the registry record.

The safety record contains serious-event and death counts by group, along with listed serious-event terms and percentages. These are descriptive observations. They do not by themselves demonstrate that an event was caused by vaccination or that the groups had comparable risk. More detail on attribution and follow-up is not reported in the registry record.

In short, the registry documents the design and endpoint definition but leaves the primary numerical result unavailable. The posted information supports a description of what was to be measured, not a conclusion about the magnitude, precision, or clinical implications of the response.

14. Why This Trial Matters Statistically

This trial is statistically notable because it combines a biological endpoint measured at surgery with a non-randomized parallel design. The primary question is framed as a response proportion among participants with a surgery-time T-cell measurement. That is a different inferential target from a randomized comparison of clinical outcomes between two groups.

The registry’s description of the optional observational control group is especially important. Control participants did not have T-cell response data collected at surgery, so the primary endpoint cannot be read as a direct vaccine-versus-control comparison. This illustrates why the analysis population and the availability of outcome measurements are essential parts of interpreting an endpoint, not merely technical details.

The registry also shows how a clearly defined response threshold can coexist with an incomplete statistical record. The endpoint definition and intended confidence-interval type are reported, but the observed rate and interval are not. Without those values, readers cannot judge either the response magnitude or its precision. Reporting the analysis population, counts, estimate, uncertainty, and missing-data approach would be necessary for a fuller statistical interpretation.

Finally, the safety record presents group-specific counts in a study that was not randomized. Those numbers can describe what was recorded, but they cannot on their own establish comparative safety. The trial therefore highlights the need to separate descriptive event summaries, biological response measures, and causal treatment comparisons when reading clinical-trial results.

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 primary limitation for interpretation is that the registry record does not report the primary endpoint result values. The response count, response proportion, confidence interval limits, and test result are unavailable. The record lists no analyses, so there is no reported analysis from which to assess the estimated effect or its precision.

The study was non-randomized and unmasked, and the comparator was an observational standard-of-care group. The groups are not a like-for-like control comparison by design. The registry further states that surgery-time T-cell response data were not collected for the optional control group, preventing a direct comparison for the primary endpoint. The record does not describe adjustment for baseline differences or other potential confounding.

The analysis included participants with a surgery-time measurement, but the registry does not report the number included in that endpoint analysis or how missing measurements were handled. The relationship between the registry’s enrollment figure and the outcome-specific populations is not explained in participant-flow detail. Information about the original sample-size justification, protocol, multiplicity approach, interim analyses, and statistical plan is not reported in the registry record.

Safety information is also limited to the reported group counts, death figures, and listed serious-event terms with percentages. Event attribution, timing, follow-up details, and event-level overlap are not reported in the registry record. These limitations mean that the available record supports a cautious description of design and recorded events, but not a complete assessment of efficacy, comparative safety, or statistical precision.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: ADXS 11-001 Vaccination Prior to Robotic Surgery, HPV-Positive Oropharyngeal Cancer — NCT02002182.
• Registry record last updated 2022-09-22; status last verified 2022-09.
• Results first posted 2020-07-02.
• 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

NCT02002182 is a completed Phase 2, parallel, non-randomized trial of ADXS11-001 before robot-assisted resection for HPV-positive oropharyngeal squamous cell carcinoma. The registry lists enrollment of 15, no masking, and an observational control group receiving standard-of-care therapy only.

The primary endpoint was the proportion of participants with a >2-fold increase in HPV-specific T-cell response from baseline to surgery, with a 95% confidence interval specified. The analysis included participants with a surgery-time measurement; the optional control group did not have that measurement collected. The registry record does not report the primary endpoint result or analyses. Safety counts are reported separately by group, but the non-randomized design does not support treating them as a causal comparison.