Efficacy and Safety Trial of ADU-S100 and Pembrolizumab in Head and Neck Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety Trial of ADU-S100 and Pembrolizumab in Head and Neck Cancer (NCT03937141), a na phase 2 study. The primary outcome is Evaluation of Clinical Activity by the Objective Response Rate (ORR; Complete Response [CR] and Partial Response [PR]) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

2. Clinical Question

The clinical question concerns antitumor activity and safety in adults with recurrent or metastatic HNSCC. The brief summary describes a first-line setting and a PD-L1 positive population. The primary endpoint was intended to capture whether participants had a confirmed complete response or partial response, rather than to compare the combination with another treatment. The record lists the response-assessment timeframe as up to 25 months.

Because this was a single-group study, its central efficacy question is descriptive: what responses were recorded among the participants included in the endpoint analysis? Without a comparator group, the trial cannot estimate a treatment contrast against another intervention or separate a treatment effect from other influences on outcomes. The registry record does not report the numerical endpoint result, so the response rate and its precision cannot be described from this record.

3. Trial Design

This was an open-label, multicenter Phase 2 trial of ADU-S100 with pembrolizumab in adults with head and neck cancer. The registry records no masking and identifies the model as single-group. Allocation is recorded as NA; no randomized comparison is described. The registry enrollment is 16.

The intervention description specifies intratumoral injections of ADU-S100 and intravenous infusions of pembrolizumab. The brief summary identifies ADU-S100 as MIW815 and describes the intended population as adults with PD-L1 positive recurrent or metastatic HNSCC in the first-line setting. The conditions are listed as metastatic and recurrent head and neck cancer.

The trial began on 2019-08-26, and the primary completion date is 2021-05-10. Its current status in the registry record is terminated. The reason for termination is not reported in the registry record. The record does not report a separate control arm, a masking procedure, or an explanation of the allocation entry beyond NA.

The single-group design is important for interpreting the efficacy question. The endpoint can describe the response experience in the analyzed participants, but there is no concurrent trial group for a direct comparison. Open-label assessment also means that masking of participants and investigators was not part of the recorded design. The record identifies the investigator as the assessor of response, and does not report independent central review.

Although the registry lists an enrollment of 16, it does not provide the primary response count or a numerical response-rate estimate. Enrollment therefore cannot stand in for the endpoint denominator: the endpoint population is described as participants with at least one post-baseline response assessment, and the count meeting that condition is not reported in the registry record.

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: All enrolled subjects were included in the trial.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Analysis performed on subjects who had ≥ 1 post-baseline response assessment.

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 participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Evaluation of Clinical Activity by the Objective Response Rate (ORR; Complete Response [CR] and Partial Response [PR]) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, measured over Up to 25 months.

The primary endpoint is objective response rate (ORR), defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) under RECIST v1.1, as assessed by the investigator. The outcome is expressed as a count of participants in the registry definition, while ORR itself is a percentage. The stated timeframe is up to 25 months.

ORR is used in oncology trials as a summary of tumor shrinkage that meets prespecified response criteria. Requiring confirmation distinguishes a response that persists on assessment from a single unconfirmed finding. RECIST v1.1 supplies standardized criteria for categorizing changes in measurable disease, supporting a consistent endpoint definition. These are general features of response endpoints; the registry record does not provide further detail about the assessment schedule or confirmation rules used in this trial.

The endpoint's stated analysis population consists of subjects with at least one post-baseline response assessment. This condition matters because participants without such an assessment are not included in the described population. The number of participants meeting the condition, the numbers with CR or PR, the total endpoint denominator, and the resulting ORR are not reported in the registry record. Consequently, the response rate and its statistical precision cannot be evaluated from the recorded endpoint information.

ORR is a measure of observed response, not by itself a comparison of outcomes against an alternative treatment. In this single-group trial, it describes responses under the combination among the analyzed participants. It does not, on its own, establish what would have happened to those participants under another treatment or without the combination.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is binary at the participant level: each participant is classified according to whether a confirmed complete or partial response was recorded under the stated criteria. The ORR is the proportion of the defined analysis population classified as a responder, expressed as a percentage. This is a general description of how a binary response endpoint is interpreted. The registry record does not report the responder count or denominator needed to give the trial's estimate.

What does a confidence interval communicate?

As a general statistical explanation, a confidence interval describes uncertainty around an estimated quantity under a specified statistical method. For a response proportion, it reflects the uncertainty arising from the observed participant-level outcomes and the size of the analyzed group. A narrower interval indicates greater precision under the chosen method; a wider interval indicates less precision. The registry record does not report an ORR confidence interval or enough endpoint counts to calculate one. No particular interval method is reported in the registry record.

Why does the analysis population matter?

The registry defines the endpoint population as subjects with at least one post-baseline response assessment. This means the stated endpoint does not automatically include everyone enrolled. The number who had an assessment and the number who did not are not reported in the registry record. As a general point, excluding participants without a post-baseline assessment can affect an estimate if the missing assessment is related to response or prognosis. The direction and magnitude of any such effect cannot be determined here, and the record does not describe a missing-data analysis.

What does a single-group analysis estimate?

For a single-group trial, a response proportion describes outcomes among participants in the analysis population who received the study combination. It does not provide a randomized between-group contrast. General statistical methods for comparing treatments rely on a suitable comparator and a defined contrast; neither is identified in this trial's design. A single-group response rate can be informative as a description of observed activity, but it cannot by itself distinguish the influence of treatment from differences in participant characteristics, disease course, or other factors.

How should the planning illustration be read?

The planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes a planning calculation based on a fraction of an observed effect, rather than the trial's own design. Those assumptions do not match the recorded single-group design, and the illustration should not be interpreted as an analysis of this trial or as observed power. Sample-size calculations are planning tools: they describe the conditions under which a hypothetical study might be designed to detect a specified effect, not the probability that a completed study's result is true. The numerical planning outputs and the observed effect used for such calculations are not reported in the registry record.

For an ordinary two-arm planning calculation, equal allocation means the hypothetical groups are assigned the same planned number of participants. That assumption is distinct from actual enrollment in this single-group trial. The normal approximation is a method for approximating the sampling distribution used in a calculation; its use in the planning illustration does not establish that it was used for the trial's endpoint analysis. The registry record does not report a sample-size justification or a statistical analysis plan.

Why can over-dispersion matter in other outcome models?

As a general statistical explanation, over-dispersion occurs when observed variability is greater than a model assumes. If it is ignored in an appropriate model, uncertainty can be understated and statistical conclusions can appear more precise than warranted. It is most relevant to particular count or rate models, not an automatic feature of a binary ORR endpoint. The registry does not report an over-dispersion adjustment or a model-based analysis for this outcome, so no such method should be attributed to this trial.

What analysis details are available?

The registry identifies the endpoint as a participant count and gives the response definition and analysis population. It does not report an inferential method, confidence-interval method, adjustment variables, prespecified analysis plan, or numerical efficacy analysis. General explanations of proportions and uncertainty cannot fill in those missing trial-specific details. The posted information therefore supports interpretation of the endpoint's intended meaning, but not reconstruction of the sponsor's primary efficacy analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. The primary outcome is ORR, defined as confirmed CR or PR under RECIST v1.1. The record does not report a multiplicity strategy, such as a procedure for adjusting interpretation across multiple statistical tests. It also does not report a statistical analysis plan that would establish which analyses or comparisons were prespecified.

Multiplicity is a general concern when multiple outcomes, comparisons, or repeated opportunities for testing are considered. Conducting many tests can increase the chance of observing a seemingly notable result by chance. A prespecified approach can define how such results are interpreted. No such approach is reported in the registry record, and no p-value or numerical efficacy analysis is listed. It is therefore not possible to assess whether multiplicity was relevant to the sponsor's analysis or how it would have been handled.

The endpoint population includes participants with at least one post-baseline response assessment. The registry does not report how many enrolled participants had such an assessment, how missing assessments were handled, or whether any imputation or sensitivity analysis was planned or conducted. It also does not describe how participants with incomplete follow-up were treated in the endpoint analysis. Those missing-data methods are not reported in the registry record.

The defined analysis population should be kept distinct from enrollment. Enrollment is listed as 16, while the endpoint denominator is not reported. Without that denominator and the response count, neither the ORR nor the completeness of response assessment can be evaluated. The record does not report a separate analysis population for safety beyond the group-level fields, or explain how participants were included in each safety summary.

These omissions limit reproducibility and interpretation. The endpoint definition is available, but the analysis details needed to reproduce the result or assess the effects of missing data and multiple testing are not 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: stress cardiomyopathy (6.2%), hypophysitis (6.2%), aphthous ulcer (6.2%), colitis (6.2%), localised oedema (6.2%).

The registry's safety group is titled ADU-S100 and Pembrolizumab. Its serious-adverse-event fields report 16 participants at risk and 16 affected. The record also reports 6 deaths. The relationship of those deaths to study treatment, their causes, and their timing are not reported in the registry record, so the death count should not be interpreted as a count of treatment-related deaths.

The listed serious-event terms are stress cardiomyopathy, hypophysitis, aphthous ulcer, colitis, localised oedema, and cytokine release syndrome. Each is shown with a percentage of 6.2%. These are registry-listed percentages; the precise denominator and whether the percentages refer to participants or event occurrences are not clarified in the record. The terms are not evidence on their own of causation by the combination.

Safety figures need their reporting context. The record does not provide narrative descriptions, timing, severity grades, duration, management, or attribution for these terms. Nor does it describe whether a participant could contribute more than one term. The serious-event fields should therefore be read as registry entries, not as a complete clinical account of each event or as a comparison with another group. There is no separate control group in this single-group trial.

Serious adverse events and deaths are different kinds of safety information and should not be conflated. The registry reports both, but the available details do not establish a relationship between them or between either category and treatment.

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

The registry record establishes that a Phase 2, open-label, single-group study evaluated ADU-S100 with pembrolizumab in adults with recurrent or metastatic head and neck cancer. It also defines the primary efficacy endpoint as ORR based on confirmed CR or PR under RECIST v1.1. Those details clarify what the trial set out to assess.

The record does not report the primary endpoint's response count, denominator, numerical rate, or confidence interval. It therefore does not establish what ORR was observed or how precisely it was estimated. Enrollment of 16 cannot be used as the endpoint denominator because the defined analysis population requires at least one post-baseline assessment, and the number meeting that criterion is not reported.

Even a reported response rate from this design would be a description of response in the analyzed single group, not a randomized estimate of comparative benefit. The study has no separate comparator group, and its open-label design does not include masking. General statistical interpretation therefore distinguishes an observed response proportion from evidence of a causal difference between treatments. The registry does not report a comparative analysis.

The safety entries document serious-adverse-event fields, event terms with listed percentages, and a death count. They do not report enough context to establish cause, attribution, or the clinical circumstances around each event. The percentages should be read as registry entries, with their denominator and participant-versus-event basis not clarified in the record.

The trial status is terminated, but the reason is not reported in the registry record. Status alone does not explain whether the endpoint data were complete, why the trial ended, or how termination affected follow-up. Thus the record supports a description of the trial design and what was intended to be measured, but it does not support a numerical conclusion about the primary efficacy result or a causal claim about efficacy or safety.

13. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an endpoint result are not the same thing. The registry specifies ORR, the response categories counted, the response criteria, and the assessment population. Those details make the intended estimand—the quantity the analysis aims to describe—more understandable. But without the responder count and denominator, the actual response estimate cannot be evaluated.

The design also illustrates a key distinction between estimating a proportion and estimating a treatment contrast. A single-group study can describe the proportion of analyzed participants who had a qualifying response. It does not include a concurrent comparator that would allow a randomized contrast. Statistical interpretation must match the design rather than treating an outcome proportion as if it were a comparative effect.

Assessment and missingness are important to the endpoint as defined. Requiring at least one post-baseline response assessment means the endpoint population may differ from total enrollment. The record does not report the size or characteristics of that population, or how missing assessments were handled. These details matter because the population included in an analysis helps determine what the resulting estimate represents.

The record also demonstrates why safety listings require careful context. Event terms and percentages do not by themselves convey timing, severity, attribution, or whether a term represents a participant or an event occurrence. A death count likewise cannot be equated with treatment-related mortality without attribution information.

Finally, planning calculations and a completed trial's evidential results answer different questions. A planning illustration rests on assumptions about a hypothetical design; it is not evidence of observed efficacy, and it cannot substitute for an endpoint estimate with uncertainty. Keeping these distinctions clear helps readers assess what the registry record documents and what remains unresolved.

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 most direct limitation is that the registry record does not report a numerical primary efficacy result. The response count, endpoint denominator, ORR estimate, and confidence interval are not reported. The record therefore does not permit assessment of the observed response rate or its precision.

The single-group, open-label design has no concurrent control group and no masking. This limits causal interpretation and leaves the response estimate, if available, descriptive rather than a randomized comparison. The record identifies the investigator as the response assessor but does not report independent central review or further assessment procedures.

The endpoint population is limited to subjects with at least one post-baseline response assessment, but the record does not report how many participants met that condition or how participants without an assessment were handled. Missing-data methods and sensitivity analyses are not reported in the registry record. This leaves uncertainty about endpoint completeness and the population represented by the intended analysis.

Enrollment is listed as 16, and the trial status is terminated. The reason for termination and its implications for enrollment, follow-up, and outcome collection are not reported in the registry record. A sample-size justification and statistical analysis plan are also not reported.

Safety entries have limited context: the registry lists serious-event terms and percentages and reports 6 deaths, but does not report attribution, timing, or supporting clinical detail. The denominator and whether listed percentages refer to participants or event occurrences are not clarified. The registry record does not provide a basis for interpreting the deaths as treatment-related or for comparing safety with another group.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety Trial of ADU-S100 and Pembrolizumab in Head and Neck Cancer — NCT03937141.
• Registry record last updated 2022-01-03; status last verified 2021-12.
• Results first posted 2022-01-03.
• 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

NCT03937141 is a terminated, open-label, multicenter Phase 2 single-group trial of intratumoral ADU-S100 with intravenous pembrolizumab in adults with recurrent or metastatic head and neck cancer. The brief summary describes a PD-L1 positive population in the first-line setting. Enrollment is listed as 16, and the registry status is terminated; the reason for termination is not reported in the registry record.

The primary endpoint is ORR, defined as confirmed CR or PR under RECIST v1.1 and assessed by the investigator, with a timeframe of up to 25 months. The analysis population is described as subjects with at least one post-baseline response assessment. The numerical response result, denominator, and uncertainty estimate are not reported in the registry record.

The safety record lists serious-adverse-event fields, serious-event terms with percentages of 6.2% each, and 6 deaths. Context needed to interpret attribution and the percentage denominator is not reported. The record lists one outcome measure and zero analyses.