GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC (NCT04251117), a na phase 1, phase 2 study. The primary outcome is Incidence of Treatment-Related Adverse Events.

2. Clinical Question

3. Trial Design

This is an open-label, multicenter Phase I/IIa study of GNOS-PV02, INO-9012 and pembrolizumab in people with advanced HCC. The registry identifies the design as single group and reports no allocation to competing study arms. Because treatment is open-label, participants and investigators are not masked to the assigned study treatment; there is no separate assigned comparator arm to mask against.

The treatment sequence described in the record begins with first-line standard-of-care tyrosine kinase inhibitor therapy while a patient-specific GNOS-PV02 vaccine is manufactured. The combination of GNOS-PV02, INO-9012 and pembrolizumab is then administered upon disease progression or intolerance to TKI. The record also lists the CELLECTRA®2000 electroporation device among the interventions. It does not give further treatment schedules in the registry record for this analysis.

The registry lists enrollment as 36 and status as active, not recruiting. The listed study start is 2020-03-01, and primary completion is 2024-11-29. The primary endpoint’s follow-up period is described as extending from first study drug administration to approximately 57 months. These record details do not establish that every participant completed follow-up or that all planned data are available.

The single-group structure is central to interpretation. The study can describe safety and other outcomes among participants who received the regimen, but it has no concurrent randomized group for estimating a comparative treatment effect. The record does not report a statistical analysis plan or a sample-size justification for the trial.

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: This was not a randomized study. All patients that met screening criteria and discontinued 1st line therapy were eligible for the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified intention-to-treat (mITT) population, defined as all enrolled patients who received at least one dose of study treatment.

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: The baseline analysis population consisted of 36 patients with advanced hepatocellular carcinoma who initiated study treatment and formed the modified intention-to-treat population.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Treatment-Related Adverse Events, measured over From first study drug administration to approximately 57 months.

The primary endpoint is the incidence of treatment-related adverse events, expressed as the number of participants affected. The registry defines a treatment-related event as one judged possibly, probably, or definitely related to study treatment. The treatment components considered in that definition include PTCV, IL-12, electroporation and/or an immune checkpoint inhibitor. Events must begin on or after the first dose and are graded according to CTCAE version 5.0. The stated observation period runs from first study drug administration to approximately 57 months.

The primary analysis population is the modified intention-to-treat population, defined in the record as all enrolled patients who received at least one dose of study treatment. This population definition makes exposure to study treatment a condition for inclusion; it is not identical to a population consisting of everyone enrolled regardless of treatment received.

Safety is an important endpoint in a Phase I/IIa study of a multi-component regimen. Counting participants with treatment-related events gives a direct description of how often such events are recorded in the defined population and follow-up period. It does not, by itself, show how event risk compares with another regimen, identify which component caused an event, or establish that an event was caused by treatment. A primary-endpoint result is not reported in the registry record, so the endpoint definition can be described but its observed result cannot.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are described in general terms where the registry record does not give a study-specific plan. The record identifies a participant-count endpoint and defines the primary analysis population, but the statistical analysis plan is not reported in the registry record.

What does a participant count describe?

For a binary outcome, each participant is classified according to whether the outcome occurred during the defined observation period. A count reports how many participants experienced the event; a proportion relates that count to an analysis denominator. The primary endpoint is specified as the number of participants with treatment-related adverse events, not as a time-to-event endpoint. The record does not report a primary count or a primary denominator result.

General: a count is easy to interpret as a description of events in a study group, but it does not alone convey how uncertain the underlying event frequency may be. Confidence intervals can express that uncertainty around an estimate. They do not establish causation, correct for selection effects, or create a comparison that the design does not contain. No confidence interval for the primary endpoint is reported in the registry record.

What does the single-group design permit?

General: in a single-group study, observed outcomes describe the group enrolled and treated under the study conditions. A treatment effect usually requires a contrast between outcomes under different treatment strategies. A concurrent control group can help estimate such a contrast, especially when allocation is randomized. This study is recorded as single group, with allocation listed as not applicable, so there is no randomized between-group contrast in the design. Comparing its outcomes with external experience would require additional information and assumptions not reported in the registry record.

Open-label treatment means masking is absent. General: awareness of treatment can influence reporting, assessment, decisions to investigate symptoms, or judgments about whether an event is treatment-related. Standardized definitions and grading criteria can support consistency, but they do not guarantee that assessment is unaffected by knowledge of treatment. The record specifies CTCAE version 5.0 for grading primary-endpoint events; further details about adjudication or blinded review are not reported in the registry record.

How should event attribution be understood?

The endpoint includes adverse events deemed possibly, probably, or definitely related to study treatment. This is a clinical attribution category, not proof of causation. The regimen includes multiple treatment components, and the endpoint description allows relationship to the study treatment components collectively. The registry record does not report a method for assigning an event to one component when several are used, nor does the primary definition identify a controlled comparison for separating treatment effects.

General: over-dispersion can matter when a count model assumes that variation in counts follows a specified distribution. If actual variation is greater than that assumption allows, standard errors may be too small and intervals too narrow. This is a general consideration for count-data analyses, not a reported feature of this study. The registry record does not state that a count model, an over-dispersion adjustment, or any particular model was used for the primary endpoint.

What is the role of sample-size planning?

General: sample-size calculations are planning tools that depend on assumptions about the effect to detect, variability, significance level, allocation and analysis method. They do not describe the observed result or demonstrate that a completed study has adequate precision. The planning illustrations associated with the posted material are not the trial’s own design justification and are not observed power. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. Because the trial itself is single group, a two-arm planning illustration should not be mistaken for the study’s actual allocation or a randomized comparison. The trial’s own sample-size justification is not reported in the registry record.

The registry lists one analysis and ten outcome measures, but does not specify the analysis method for the primary endpoint. It does not report whether estimates were adjusted, how repeated assessments were handled, or whether any interim analyses were planned or conducted. These details should not be inferred from the endpoint labels or study phase.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety endpoint and secondary outcomes covering response, duration of response, disease control, progression-free survival and overall survival. Several outcomes have related definitions, including response and progression-free survival assessed by iRECIST. When many outcomes are examined, the chance of at least one apparently notable result can increase. General statistical approaches to multiplicity include prespecifying a primary comparison or adjusting inference across tests. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how the secondary outcomes were treated as a family of analyses.

The primary analysis population is defined as enrolled patients who received at least one dose of study treatment. The record does not describe the population used for each secondary outcome, or how participants with no post-baseline assessment were handled. The number and pattern of missing outcome data, reasons for missingness, and methods for handling missing observations are not reported in the registry record.

General: missing data can affect interpretation when the chance of having an observed outcome is related to a participant’s health, treatment exposure or outcome. Analyses based only on observed assessments can then differ from the results that would have been seen with complete follow-up. The direction and size of such effects depend on the missingness process and analysis choices; they cannot be determined from the endpoint definitions alone.

The record does not report a statistical analysis plan, prespecified testing sequence, adjustment for multiplicity, or sensitivity analyses for missing data. These omissions limit assessment of how robust any later reported secondary findings would be. They do not show that a particular method was or was not used outside the information 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (5.6%), lower respiratory tract infection (5.6%), pneumonia (5.6%), pulmonary embolism (5.6%), anaemia (5.6%).

The registry safety record lists one treatment group and reports 19 participants with serious adverse events among 36 at risk, 27 with other adverse events among 36 at risk, and 24 deaths. These are distinct safety summaries and should not be combined into a single count. The record does not state that all serious or other adverse events were judged related to treatment. Those summaries therefore should not be read as the primary treatment-related adverse-event endpoint.

The listed serious adverse event terms include abdominal pain, lower respiratory tract infection, pneumonia, pulmonary embolism and anaemia, each reported at 5.6%, and abdominal pain upper at 2.8%. These are term-specific registry entries, not evidence that every participant had each event. The record does not provide further information about event timing, severity beyond the serious-event classification, recurrence, or attribution for these terms.

The death count does not identify cause or relationship to treatment. It also does not establish when deaths occurred relative to follow-up or whether all participants had completed observation. A count alone cannot support causal conclusions. The primary endpoint’s treatment-related definition and the broader safety categories should be interpreted separately.

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

The registry record establishes that this is an open-label, single-group Phase I/IIa study of GNOS-PV02, INO-9012 and pembrolizumab in advanced HCC, with a described treatment sequence involving TKI therapy during personalized vaccine manufacture. It defines a primary safety endpoint and the population intended for its analysis. It also records safety counts and a list of serious adverse event terms.

These details do not establish whether the regimen improves response, disease control, progression-free survival or overall survival. Although the registry lists those secondary outcomes, their results are not reported in the registry record. The primary treatment-related adverse-event result is also not reported. Thus, the safety endpoint’s definition should not be confused with its observed value, and the list of planned outcomes should not be treated as evidence of their results.

The absence of a control group means that outcomes in the study cannot be interpreted as a comparative treatment effect. Even a complete account of observed events would describe what happened among participants in this study, rather than show what would have happened to comparable participants under another treatment. The design also does not isolate the effects of the vaccine, IL-12, pembrolizumab or electroporation.

Safety counts are not the same as causal findings. Serious adverse events, other adverse events, deaths and events judged treatment-related are different categories. The registry does not attribute every serious event or death to the study treatment. The reported counts should therefore be read as descriptive safety information, with the endpoint-specific definitions kept in view.

Overall, the record supports a careful description of study design, outcome definitions and recorded safety summaries. It does not support a conclusion about comparative benefit, treatment efficacy, causal safety effects or the precision of the primary endpoint. Those judgments would require outcome results and methods details not reported in the registry record.

13. Why This Trial Matters Statistically

This study raises statistical questions that are common in early-phase research on personalized and multi-component regimens. The primary endpoint is a safety measure, while the registry also lists response and survival outcomes. Keeping the endpoint definitions separate is important: a safety count, an objective response measure and a time-to-event outcome answer different questions and require different interpretations.

The single-group design makes descriptive estimation central. It can characterize events among treated participants, but it does not provide a randomized control contrast. This distinction matters when interpreting outcomes in a disease setting where participants may receive other care as part of the treatment sequence. The record describes TKI therapy before the combination is administered upon progression or intolerance, but it does not offer a separate comparison group for estimating the effect of that sequence.

The personalized manufacturing period also makes the stated sequence relevant to defining exposure and follow-up. The primary safety window begins at first study drug administration, and the endpoint population requires at least one dose of study treatment. Clear reporting of who enters each analysis and when follow-up begins is important for interpreting both event counts and time-to-event outcomes.

Finally, the registry’s outcome list is broader than its reported results. Statistical interpretation depends not only on which outcomes were selected, but also on the results, precision, missing-data handling and multiplicity strategy. Those methods and primary results are not reported in the registry record. The study is therefore statistically informative as a design and endpoint description, while substantive conclusions about outcomes remain limited by the information recorded.

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 single-group, open-label design is the main limitation for comparative interpretation. There is no randomized control arm, so outcome differences against another treatment strategy cannot be estimated within the study. Open-label assessment may also affect event reporting or attribution; the record specifies CTCAE version 5.0 but does not report blinded event review or adjudication procedures.

The primary endpoint is treatment-related adverse events, but its observed result is not reported in the registry record. The listed safety counts do not replace that endpoint because the categories are not stated to be restricted to events judged related to treatment. The causes of the reported deaths are not provided. Further details on event timing, follow-up completeness and participant-level exposure are also not reported.

The study includes a treatment sequence in which TKI therapy is given while the personalized vaccine is manufactured, and the combination is administered upon disease progression or intolerance to TKI. This means outcomes relate to a sequence of care, not simply to an isolated exposure beginning at enrollment. The record does not provide details sufficient to evaluate how time on TKI, progression, intolerance or manufacturing affected inclusion in later treatment or analysis.

Although secondary outcomes are listed, their results and analysis populations are not reported. Missing-data methods, multiplicity handling, the primary statistical analysis method, and the trial’s sample-size justification are not reported in the registry record. The listed enrollment does not by itself establish how many participants contributed to any particular endpoint analysis or how precise an estimate would be.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects With Advanced HCC — NCT04251117.
• Registry record last updated 2026-09-24; status last verified 2026-04.
• Results first posted 2026-09-24.
• 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

The registry describes NCT04251117 as an open-label, multicenter Phase I/IIa, single-group study of GNOS-PV02, INO-9012 and pembrolizumab in advanced HCC. The treatment description includes standard-of-care TKI therapy during personalized vaccine manufacture, with the combination administered upon progression or intolerance to TKI.

The primary endpoint is the number of participants with treatment-related adverse events in a modified intention-to-treat population, from first study drug administration to approximately 57 months. The primary result and results for the listed secondary outcomes are not reported in the registry record. The safety record lists serious and other adverse event counts, deaths and selected serious-event terms, but does not establish that those events or deaths were caused by treatment.

Because the study has no comparator group, its design supports description of outcomes in the study group rather than a randomized estimate of comparative effects. The registry record does not report the statistical analysis plan, missing-data approach or multiplicity strategy.