Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer (NCT03162224), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs).

2. Clinical Question

The central question is therefore about safety and tolerability during treatment and follow-up, alongside descriptive assessment of anti-tumor activity and immune response. The record’s design does not support interpreting differences between the listed participant groups as randomized treatment effects. Group membership reflects clinical setting and platinum history, and the record does not describe a control group assigned to a different treatment. The figures should be read as observations within this study rather than as evidence that the combination is better or worse than another option.

3. Trial Design

This was a Phase 1b/2a, multi-center, open-label study of MEDI0457 combined with durvalumab in participants with recurrent or metastatic HPV-associated head and neck squamous cancer. The registry classifies the allocation as non-randomized and the model as single-group. Participants and study staff were not masked, as the masking entry is none. The record lists enrollment of 35, and the study status is completed.

The study started on 2017-06-26, with primary completion recorded as 2021-03-19. The brief description says an initial three to 12 participants would form a safety analysis run-in and be assessed for safety before additional participants were enrolled. It also describes an approximate total of 50 participants for evaluation of safety and anti-tumor efficacy. The registry’s enrollment field lists 35; the record does not explain the difference between that listing and the approximate enrollment described in the brief summary.

Participant groups were organized by treatment setting and platinum history: first-line recurrent or metastatic platinum non-refractory disease, first-line recurrent or metastatic platinum-refractory disease, and second-line or later recurrent or metastatic disease. These categories are not randomized arms. The record describes MEDI0457 administration with electroporation and durvalumab administration, with schedules differing in the arm descriptions. Some regimen text is truncated in the registry record, so the complete treatment-stopping criteria and details are not reported in the registry record.

The primary measure counted participants with treatment-emergent adverse events and serious adverse events in the as-treated population, defined as participants who received at least one dose of any study drug. Secondary outcomes listed include objective response using RECIST Version 1.1 and immune-related RECIST, disease control at Week 16, progression-free survival, overall survival, and positive anti-drug antibodies to durvalumab. The record does not list inferential analyses for these outcomes. Its primary endpoint description specifically says that updated results would not be available for that outcome at the end of the study.

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: The data are reported per the data cut-off (DCO) date of 19Mar2021 and the data after DCO will not be entered into the clinical study database and hence, will not be analyzed.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: As-treated population included all participants who received at least one dose of any study drug.

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: As-treated population included all participants who received at least one dose of any study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), measured over Day 1 through 90 days after the last dose of study drug (approximately 45 months).

The primary endpoint is the number of participants with treatment-emergent adverse events and treatment-emergent serious adverse events. An adverse event is defined in the registry as an untoward medical occurrence after a participant received study drug, without requiring a causal relationship. A treatment-emergent event is one that was absent at baseline and appeared after treatment, or was present at baseline and worsened in intensity after treatment.

The serious-event definition covers events resulting in death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, or a congenital anomaly. An event may also be deemed serious for another significant reason. These criteria distinguish serious events by their consequences or significance, rather than by whether investigators judge the study drug to have caused them.

The stated observation window runs from Day 1 through 90 days after the last dose of study drug, approximately 45 months. Counting participants who experienced an event gives a straightforward description of how many treated participants had an event during the defined period. This is useful in a safety-focused early-phase study, where tolerability and the nature of adverse events are important outcomes. A count alone does not indicate event severity beyond the serious-event classification, establish causality, or capture the number of separate events experienced by each participant.

The primary outcome description states that updated results would not be available at the time of end of study. Accordingly, the endpoint’s definition and follow-up window are reported, but updated primary outcome results are not reported in the registry record. The posted group safety figures should not be mistaken for a complete updated analysis of this primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported design is a non-randomized, open-label, single-group study. These features matter when interpreting both safety and efficacy outcomes. Random allocation can help balance measured and unmeasured characteristics between treatment groups; this study did not use random allocation. Open-label means masking was absent. A single-group study can describe outcomes among participants receiving the study regimen, but it cannot by itself separate treatment effects from the course of disease, participant characteristics, or other care.

What does a participant count measure?

The primary outcome is a count of participants with treatment-emergent adverse events and treatment-emergent serious adverse events. A participant count records whether a person had at least one event meeting the endpoint definition during its observation period. It is not a count of every episode or a measure of event duration. Participants can have more than one event, and a participant with multiple events may still contribute once to a participant-level count for a given category. The registry record does not provide a detailed counting algorithm for overlap between event categories.

The safety figures also list participants at risk and participants affected for each clinical group. These denominators make the counts interpretable within their stated groups. They do not, on their own, establish that one group has higher risk than another. The groups differ by clinical setting and platinum history and were not randomized. A comparison would need to account for those differences and for other prognostic characteristics, and such an adjusted analysis is not reported in the registry record.

Why distinguish serious from other adverse events?

The registry’s serious adverse event definition is based on specified consequences or clinical significance, including death, hospitalization, life-threatening experience, disability or incapacity, and congenital anomaly. Seriousness is not the same as relatedness: the event definition does not require investigators to conclude that study drug caused it. Likewise, treatment-emergent describes when an event arose or worsened relative to treatment, not its cause. These distinctions are important when reading safety summaries. The registry record does not provide attribution results alongside the counts.

How should response and survival outcomes be understood?

The listed secondary outcomes use response criteria including RECIST Version 1.1 and immune-related RECIST. The record also lists disease control at Week 16, progression-free survival, and overall survival. These outcomes answer different questions: response criteria classify tumor change under specified rules, while time-to-event outcomes concern the time until an event defined by the relevant endpoint. The registry record does not provide analyses, estimates, confidence intervals, or event definitions for these outcomes in the registry entries. No numerical efficacy conclusion can therefore be drawn from the outcome titles alone.

For time-to-event outcomes, general statistical explanation: participants may have different follow-up durations, and some may not experience the event before observation ends. Methods for censored time-to-event data use the observed follow-up while accounting for that incomplete event information. No particular estimator, censoring rule, hazard model, or analysis result is reported in the registry record for progression-free or overall survival.

What do the planning assumptions mean?

The sample-size section describes planning illustrations based on the observed effect, not the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is a total number of events using the Schoenfeld approach, while other illustrations are expressed as participants per arm. These are hypothetical planning calculations, not results observed in this study and not observed power. The registry record does not report the trial’s sample-size justification or original design assumptions.

General statistical explanation: a planning calculation asks what sample size might be needed under chosen assumptions to detect a specified effect with a chosen operating characteristic. It does not show that a completed study had that probability of finding an effect, and it does not repair the limitations of a non-randomized design. A calculation based on an observed effect can also be sensitive to how that effect was estimated. The figures should therefore be treated as planning illustrations rather than as a retrospective verdict on the study’s success.

What is not reported about the statistical plan?

The registry record lists zero analyses. It does not report the planned statistical tests, estimation methods, confidence-interval procedures, adjustment for prognostic factors, interim analyses, or rules for dealing with missing endpoint data. It also does not report a multiplicity strategy for the several secondary outcomes. General statistical explanation: multiplicity arises when several outcomes or comparisons are assessed, because repeated testing can increase the chance of at least one apparently noteworthy result. Without a reported plan and inferential results, there is no basis to assess how that issue was handled in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including response by RECIST Version 1.1 and immune-related RECIST, disease control at Week 16, progression-free survival, overall survival, and anti-drug antibodies to durvalumab. It also describes safety, anti-tumor activity, and immunogenicity as study aims. The registry record does not report a hierarchy among these outcomes, a prespecified multiplicity adjustment, or an analysis plan explaining how conclusions across multiple measures were to be controlled.

General statistical explanation: when investigators examine several outcomes, the chance of at least one apparently notable result can rise if each is assessed separately. A prespecified testing sequence or an adjustment can address that issue, but neither should be assumed without documentation. Since no analyses are listed, the record does not permit review of any multiplicity procedure or its effect on interpretation.

The record defines the primary safety population as as-treated: participants who received at least one dose of any study drug. It also names response-evaluable and as-treated populations for some secondary outcomes. The criteria for being response-evaluable are not reported in the registry record. The available information does not describe how participants with missing assessments, incomplete follow-up, treatment discontinuation, or other missing data were handled. The extent and reasons for missing data are also not reported in the registry record.

These omissions limit the ability to assess whether the analyzed participants represent everyone enrolled or how incomplete outcome information may affect results. They do not justify assuming a particular imputation, exclusion, or censoring method. The primary endpoint description further states that updated results would not be available at the time of end of study, so an updated analysis of the endpoint cannot be evaluated from 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (18.2%), tracheal obstruction (11.1%), haemoptysis (11.1%), laryngeal oedema (11.1%), respiratory failure (11.1%).

The safety figures report, by clinical group, the number at risk, the number with serious adverse events, the number with other adverse events, and the number of deaths. For serious adverse events, the registry lists 4 of 15 in the first-line platinum non-refractory group, 4 of 9 in the first-line platinum-refractory group, and 6 of 11 in the second-line or later group. The figures for other adverse events are 15 of 15, 9 of 9, and 11 of 11, respectively.

These are descriptive participant counts in groups defined by clinical setting, not results from randomized treatment arms. The study did not include a like-for-like control group, so the counts cannot establish comparative risk. The counts also do not show how many separate events occurred, how long they lasted, or whether study staff considered them related to treatment.

Deaths are listed as 4, 5, and 8 across those groups. The available record does not give cause, timing, or attribution with these figures. The listed serious-event terms and percentages are pneumonia at 18.2%, tracheal obstruction at 11.1%, haemoptysis at 11.1%, laryngeal oedema at 11.1%, respiratory failure at 11.1%, and atrial fibrillation at 11.1%. The denominator for these percentages is not reported in the registry record. The primary endpoint description also notes that updated results for that outcome would not be available at end of study.

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

The registry record supports a limited descriptive account: this completed, open-label, non-randomized study evaluated MEDI0457 with durvalumab in participants with HPV-associated recurrent or metastatic head and neck squamous cancer. It defines a primary safety outcome, gives selected serious adverse-event counts by clinical group, and lists response, survival, and immunogenicity outcomes. These details clarify what the study set out to assess and how some safety observations were categorized.

They do not establish whether the combination improves outcomes, whether it is more or less effective than another treatment, or whether it changes the risk of adverse events compared with a control. The groups were not randomized comparisons, and no inferential analyses are listed. The primary outcome description states that updated results would not be available at the time of end of study. The listed secondary outcome names cannot substitute for their missing estimates and analyses.

The adverse-event figures show that serious events and deaths were recorded in each of the clinical groups, while the listed counts for other adverse events include every participant at risk in each group. Those observations are relevant to describing the study experience, but their interpretation is constrained by the absence of an appropriate randomized comparator, details on attribution, and further context about event timing and causes. The listed serious-event term percentages also lack a stated denominator in the record.

General statistical explanation: an observed count is not a precise estimate of the underlying frequency, especially when the group is limited in size. Confidence intervals can communicate uncertainty around an estimate, but none are reported for the figures discussed. The record also does not provide the missing-data approach or analysis details needed to evaluate how complete the outcome assessments were. The result is a registry record with useful design and safety descriptions, but insufficient reported analysis to support a comparative or causal conclusion.

13. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the role of early-phase, non-randomized evidence in documenting safety and exploring activity. Its Phase 1b/2a design combined a safety analysis run-in with evaluation of anti-tumor activity and immunogenicity. The registry’s description of that run-in makes clear that safety assessment was an important part of the study’s rationale, while the primary endpoint formalized that focus through counts of treatment-emergent adverse events and serious adverse events.

The record also shows why design labels matter. The clinical groups distinguish treatment setting and platinum history, but the non-randomized single-group model means they cannot serve as randomized controls for one another. Readers need to separate descriptive counts from causal comparisons, particularly when group characteristics and treatment schedules differ. That distinction is central to interpreting safety data as well as any future response or survival findings.

Another statistical lesson concerns the gap between an outcome being listed and its results being available. A registry may specify several outcomes, populations, and follow-up periods without displaying an analysis for each. Here, the record lists secondary response, disease-control, survival, and antibody outcomes, but reports zero analyses, and the primary endpoint description says no updated results would be available at study end. Outcome definitions alone do not answer the clinical question.

Finally, the sample-size section is explicitly a planning illustration based on an observed effect, not the study’s original design or observed power. That distinction helps prevent retrospective calculations from being mistaken for trial evidence. Together, the design and reporting details reinforce a broader principle: statistical interpretation depends not only on the values recorded, but also on allocation, outcome definitions, analysis populations, uncertainty, and completeness of reporting.

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 study constrain interpretation. The design was non-randomized, open-label, and single-group, with no like-for-like control comparison. The three reported clinical groups reflect different treatment settings and platinum histories, so their safety counts should not be interpreted as treatment effects or as direct comparisons of risk. The record does not describe an adjusted comparative analysis.

The registry lists enrollment of 35, while its brief summary describes an approximate total of 50 participants and an initial run-in of three to 12 participants. The record does not reconcile those statements. Some treatment schedule descriptions are truncated, limiting review of the complete regimen details. The record also does not provide complete information on treatment discontinuation or follow-up beyond the stated primary endpoint window.

The primary endpoint is defined, but its description says updated results would not be available at study end. No analyses are listed. Although the registry gives group counts for serious and other adverse events and deaths, it does not provide the context needed to interpret the listed deaths by cause, timing, or attribution. The serious-event term percentages are presented without a denominator in the available record.

For secondary outcomes, the record provides outcome titles but not estimates, confidence intervals, or analysis details. It does not report criteria for the response-evaluable population, missing-data procedures, censoring rules for survival analyses, multiplicity methods, or planned interim analyses. The sample-size information is a planning illustration based on an observed effect, not the trial’s reported original justification. These limitations prevent detailed assessment of precision, analysis choices, or comparative efficacy.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer — NCT03162224.
• Registry record last updated 2022-08-25; status last verified 2022-08.
• Results first posted 2022-08-25.
• 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

NCT03162224 is a completed Phase 1b/2a, multi-center, open-label, non-randomized, single-group study of MEDI0457 with durvalumab in HPV-associated recurrent or metastatic head and neck squamous cancer. The registry lists enrollment of 35, a start date of 2017-06-26, and primary completion on 2021-03-19.

The primary outcome counted participants with treatment-emergent adverse events and treatment-emergent serious adverse events from Day 1 through 90 days after the last dose, approximately 45 months. The record states that updated results for this outcome would not be available at study end and lists zero analyses. It also lists secondary response, disease-control, survival, and anti-drug antibody outcomes.

Descriptive safety counts are listed across three clinical groups, but there is no randomized comparator. The available record does not support causal or comparative conclusions about safety or efficacy.