VB-111 in Surgically Accessible Recurrent/Progressive GBM: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for VB-111 in Surgically Accessible Recurrent/Progressive GBM (NCT04406272), a randomized phase 2 study. The primary outcome is Tumor Infiltrating T Cell (TIL) Density.

2. Clinical Question

The official title frames the study as a randomized, controlled phase II surgical trial focused on early immunologic pharmacodynamic parameters for ofranergene obadenovec, also called VB-111. The clinical question is therefore narrower than whether treatment changes a clinical outcome such as survival or tumor progression. The registered primary endpoint was a measure of immune cells in tumor tissue, while progression-free survival at six months and overall survival were listed as secondary outcomes. Results for those secondary outcomes are not reported in the registry record.

The study was terminated after accrual of 15 of 45 planned patients. The record states that no TIL density data were generated because the planned analysis was not performed. Consequently, the intended comparison has no observed estimate, confidence interval, or test result in the registry record. The study's randomized design does not change that absence: random assignment can support comparisons only when the relevant outcome data are collected and analyzed.

3. Trial Design

This was a phase II, randomized, double-masked, parallel-group study sponsored by Dana-Farber Cancer Institute. The registry lists glioblastoma and recurrent glioblastoma as conditions. The trial concerned surgically accessible recurrent or progressive glioblastoma and included a surgical component. It started on 2020-08-01, had a primary completion date of 2024-08-01, and is recorded as terminated. The enrollment was 15; the primary endpoint description states that 45 patients had been planned.

The three registered groups differed in treatment timing and post-surgery management. Group A received VB-111 before and after surgery. The description says VB-111 was administered intravenously 14-28 days before surgery and, after recovery within 28-35 days after surgery, every 6 weeks. It also says participants with disease progression may initiate bevacizumab, but the complete conditions for that use are not reported in the registry record.

Group B received placebo before surgery and VB-111 after surgery. The description gives the same pre-surgery timing for placebo and states that post-surgery VB-111 was given after recovery. Group C received placebo before surgery and standard of care after recovery, with treatment every 6 weeks until tumor growth was evidenced at two consecutive time points. Further detail about the standard-of-care regimen is not reported in the registry record.

The design labels indicate random allocation, double masking, and parallel groups. The identity of the people masked, the allocation procedure, and the allocation ratio are not reported in the registry record. Nor does the record report whether treatment adherence or departures from assigned treatment were analyzed. Although the trial is described as controlled, the planned primary comparison combined Groups B and C and contrasted that combination with Group A. The registry does not report a completed analysis for this contrast. The termination and limited accrual are important context for interpreting the absence of endpoint results, but the reason for termination 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.

NeoAdjuvant Treatment

Adjuvant Therapy (Post-surgical)

Analysis population for the primary outcome, as defined in the registry: TIL Density Analysis was not - and will not be - performed on study samples, therefore no data was generated for this study objective. Because the trial was stopped after accrual of only 15 of 45 planned patients, it is believed that any results generated would not be of value, as there is no meaningful correlation that could be be drawn.

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 Tumor Infiltrating T Cell (TIL) Density, measured over 2 years.

The planned primary endpoint was tumor-infiltrating T-cell density, or TIL density. The registry defines this as the number of T lymphocytes per nucleated cell. The intended measurement method was detailed sequencing of recombined T-cell receptor sequences obtained from tumor specimen genomic DNA. This is a tissue-based measure: it characterizes immune-cell presence in sampled tumor tissue rather than directly measuring tumor growth, symptoms, or survival.

As a pharmacodynamic endpoint, TIL density was intended to capture a biological response associated with the study treatment strategy. Such endpoints can help characterize whether an intervention is associated with a change in a biological process. They do not, by themselves, establish that a clinical outcome has changed. The registry listed progression-free survival at six months and overall survival as secondary outcomes, but no results for those measures are reported in the registry record.

The planned comparison was Group A versus the combined Group B and Group C, with a two-sample t-test and tumor-size stratification described in the endpoint record. However, TIL density analysis was not and will not be performed on study samples. The record says no data were generated for this objective and explains that the trial stopped after accrual of 15 of 45 planned patients. There is therefore no observed TIL density result to interpret, and the biological endpoint cannot be used to draw a treatment comparison from this trial record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods described for the primary endpoint were a two-sample t-test with tumor-size stratification, comparing Group A with the combined Group B and Group C. That is the planned method, not a completed analysis: the registry states that no TIL density data were generated and that the analysis will not be performed. It is therefore important to distinguish the planned statistical approach from an estimated treatment contrast. No test statistic, p-value, confidence interval, or group-level TIL density estimate is reported in the registry record.

What would a two-sample t-test address?

In general, a two-sample t-test evaluates whether the mean of a continuous outcome differs between two groups, using the observed values and their variability. In this trial, the stated endpoint is a density measure and the planned comparison combined two groups for comparison with Group A. Stratification by tumor size indicates that tumor size was to be accounted for in the comparison, but the registry does not report the stratification categories, the precise model specification, or the way the stratification would enter the test. No further assumptions or adjustment details are reported.

General interpretation of a test result depends on both the estimated difference and its uncertainty. A p-value, if reported, would describe how compatible the data are with a specified null model under the test's assumptions; it would not describe the probability that the null hypothesis is true. A confidence interval would show a range of values compatible with the data and model at a stated confidence level. Neither kind of inferential result is available for the primary endpoint in this record. Because no endpoint data were produced, it is not possible to assess observed variability, distributional assumptions, or the precision of a group contrast.

What does the randomized parallel design contribute?

In general, random allocation is used to reduce systematic differences between treatment groups at baseline, while a parallel design assigns participants to a group whose assigned strategy is followed over the study period. The registry labels this trial randomized and parallel, and lists three groups. It does not report the randomization sequence, allocation concealment procedures, allocation ratio, or the identity of those who were masked. These features can affect how confidently a reader evaluates implementation of a design, so they should not be inferred from the labels alone.

The planned endpoint contrast was Group A versus the combined Groups B and C, rather than a separate reported contrast for each group. Combining groups can define a focused comparison when the scientific question calls for it, but its meaning depends on the treatment strategies being combined. Here, the registry descriptions distinguish the groups by their pre-surgery assignment and post-surgery management. No completed result is reported for the combined comparison or for separate group comparisons.

How should the absent analysis be understood?

The registry describes a planned endpoint assessment and a planned test, but it also states that the tissue analysis was not and will not be performed. This is not a null result or a non-significant result. A non-significant test would require observed data and a completed analysis; no such analysis is reported. It is also not possible to use the lack of a result to estimate the magnitude or direction of a biological response.

General statistical precision depends on the amount and quality of outcome information, not solely on the study's phase or design label. The record says 15 of 45 planned patients were accrued before the trial stopped. It does not report a completed sample-size justification, the assumptions behind the planned enrollment, or whether any interim analyses were conducted. Those items should not be reconstructed from the enrollment count or from the stated test.

How should other outcomes and safety counts be read?

Progression-free survival at six months and overall survival are listed as secondary outcomes. General time-to-event analysis accounts for both the timing of events and incomplete follow-up, but the registry record does not report outcome estimates, follow-up summaries, censoring details, or a statistical method for these outcomes. No conclusions about their distributions or comparative effects can therefore be drawn from their listing alone.

The adverse-event information is descriptive. Counts of participants at risk and affected indicate how many participants contributed to the respective recorded categories, while death counts are separately reported. General safety comparisons require careful attention to definitions, observation periods, event attribution, and exposure; those details and inferential comparisons are not reported in the registry record. The counts should not be transformed into rates or interpreted as evidence of treatment causality without the relevant information.

Multiplicity concerns arise when multiple outcomes, groups, time points, or tests are considered. In general, testing several hypotheses can increase the chance of at least one apparently notable result unless the analysis plan addresses that issue. The record lists a primary endpoint and secondary outcomes, but a multiplicity strategy is not reported in the registry record. It also does not report an analysis plan for missing outcome data, analysis populations, or handling of protocol deviations. These omissions prevent assessment of how a completed analysis would have dealt with multiple comparisons or incomplete data.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies TIL density as the primary endpoint and lists progression-free survival at six months and overall survival as secondary outcomes. It reports four outcome measures in total, but zero analyses. The record does not report a strategy for controlling multiplicity across outcomes, groups, time points, or statistical tests. Without that information, it is not possible to assess whether or how the possibility of multiple testing was considered.

The primary endpoint has no observed data: the registry states that TIL density analysis was not and will not be performed and that no data were generated. Missing-data methods for this endpoint are therefore not reported in the registry record. Results for the secondary outcomes are also not reported, and the registry does not describe censoring, loss to follow-up, imputation, or other procedures for incomplete outcome information. Those methods should not be inferred.

The record does not identify analysis populations, such as whether a completed analysis would have used all randomized participants or a subset. It also does not report how participants who did not follow their assigned strategy, withdrew, or had unevaluable specimens would have been handled. No analysis population or missing-data approach can be assumed from the randomized design alone.

The trial accrued 15 of 45 planned patients before it was stopped. This is relevant context for the lack of endpoint data, but it does not disclose a sample-size justification or tell readers whether any interim analysis occurred. Interim analyses and stopping rules are not reported in the registry record. Because no primary outcome analysis was completed, there is no basis for evaluating its multiplicity adjustment, missing-data handling, or population definition.

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: generalized muscle weakness (25.0%), skin & subcutaneous tissue disorders - other, specify: preseptal cellulitis (25.0%), memingitis (20.0%), injury, poisoning and procedural complications - other, specify: pseudomeningocele (20.0%), investigations - other, specify: elevated wbc in csf (20.0%).

The registry reports serious adverse events, other adverse events, and deaths by group. For Group A, 6 participants were at risk for serious adverse events and 3 were affected; 6 were at risk for other adverse events and 6 were affected; 3 deaths were recorded. For Group B, the corresponding figures are 4 at risk and 1 affected for serious adverse events, 4 at risk and 4 affected for other adverse events, and 2 deaths. For Group C, the figures are 5 at risk and 2 affected for serious adverse events, 5 at risk and 5 affected for other adverse events, and 5 deaths.

These are descriptive counts, not estimates of causal treatment effects. The registry record does not report statistical comparisons, event attribution, or enough detail about observation periods to establish that differences in counts reflect differences in treatment-related risk. Deaths are recorded separately; the record does not say that they were caused by treatment.

The registry also lists serious adverse event terms with percentages: generalized muscle weakness and preseptal cellulitis are each listed at 25.0%; meningitis, pseudomeningocele, elevated WBC in CSF, and confusion are each listed at 20.0%. These entries describe reported terms, but the record does not provide additional context in the reported list to support causal interpretation. A listed event term or percentage should not be read as proof that a study intervention caused the event.

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

The primary endpoint result does not answer the planned biological comparison. TIL density was intended to measure T lymphocytes per nucleated cell in tumor tissue using sequencing of recombined T-cell receptor sequences. However, the registry states that this analysis was not and will not be performed and that no data were generated. There is no reported estimate of the endpoint for any group and no basis for concluding that the groups did or did not differ.

The trial's status as a randomized phase II study does not make an unmeasured endpoint interpretable. Randomization is a design feature intended to support fair comparison, but a treatment contrast still requires outcome measurements and an analysis. The record describes accrual of 15 of 45 planned patients before the trial was stopped. It does not report a completed primary analysis, a reason for termination, or details of an interim decision process.

The record lists progression-free survival at six months and overall survival as secondary outcomes, but does not report results for either. Their presence in the registry does not establish that either outcome favored one group or that any difference was absent. No statement about clinical efficacy can be supported by the posted outcome information.

The available safety counts provide a descriptive account of participants recorded as at risk or affected and of deaths by group. They cannot, without additional information and an appropriate analysis, distinguish events caused by treatment from events associated with the disease, surgery, or other care. They also do not by themselves quantify comparative risk. The serious adverse event terms are likewise descriptions, not causal findings.

More generally, absence of a reported result is different from a result showing no effect. A result showing no clear difference would still require observed outcome data and uncertainty estimates. Here, the planned primary measure was not generated, and secondary outcome estimates are not reported. The appropriate conclusion is therefore about the limits of the record: it documents the study design, enrollment, endpoint plan, and some safety counts, but it does not provide evidence to resolve the planned TIL density question or the listed clinical outcome questions.

13. Why This Trial Matters Statistically

This trial illustrates why a registry entry needs to be read as a record of both design and results. The trial was designed around an immunologic pharmacodynamic endpoint in surgically accessible recurrent or progressive glioblastoma, with treatment strategies that differed before and after surgery. Yet the primary tumor-tissue measurement was not carried out. As a result, the scientific question articulated in the endpoint plan remains unanswered by the posted results.

Statistically, it is important to distinguish a missing result from an estimate near zero or a test that fails to reach a threshold. The registry does not report a TIL density estimate, a confidence interval, or a test result. There is thus no estimate whose precision can be evaluated and no evidence that can be described as supporting equivalence or no difference. This distinction helps prevent readers from treating an unperformed analysis as a negative finding.

The enrollment information also matters for interpretation. The record says 15 of 45 planned patients accrued before the trial stopped. This indicates that enrollment did not reach the planned total, but the registry does not explain why the study ended or provide a sample-size justification. The enrollment count alone cannot establish what the study could have detected, and it cannot substitute for an observed endpoint comparison.

The entry also separates a planned biological endpoint from listed clinical outcomes. TIL density is not itself a survival or progression result. Although progression-free survival at six months and overall survival appear among the secondary outcomes, their results are not reported. Keeping endpoint types distinct avoids attributing clinical meaning to a biological measure or assuming an outcome result from an outcome's registration.

Finally, the serious adverse event and death counts demonstrate the limits of descriptive safety summaries. They can show what was recorded by group, but not whether an intervention caused an event or whether groups differ in risk. This is a useful statistical lesson: design labels, outcome listings, and event counts each answer different questions, and none can replace a completed, interpretable analysis of the relevant endpoint.

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 planned primary endpoint was not measured. The registry states that TIL density analysis was not and will not be performed, so no primary endpoint data were generated. This prevents estimation of the intended comparison between Group A and the combined Group B and Group C and rules out assessing its uncertainty from this record.

Accrual was limited to 15 of 45 planned patients, according to the endpoint description. The registry status is terminated, but the reason for termination is not reported in the registry record. The record does not provide a completed sample-size justification, so the planned enrollment should not be treated as evidence of a particular detectable effect or precision.

The trial's design details are also incomplete for independent evaluation. Although the record labels the study randomized, double-masked, and parallel, it does not report the allocation ratio, randomization procedure, who was masked, or further details of treatment implementation. The description of bevacizumab use is incomplete, and the full details of standard-of-care treatment are not reported.

Secondary outcome results are not reported. The record does not describe follow-up completeness, censoring, missing outcome handling, analysis populations, or whether an interim analysis was conducted. It also does not report how multiplicity across outcomes or comparisons was handled. These gaps limit evaluation of the analysis plan beyond the stated primary test.

Safety information is presented as counts and listed terms, without reported statistical comparisons or sufficient information to assess event attribution and comparative risk. The counts should therefore be read as descriptive rather than as treatment effects. Taken together, these limitations mean the registry entry documents trial intent and some safety information but cannot support a completed efficacy analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: VB-111 in Surgically Accessible Recurrent/Progressive GBM — NCT04406272.
• Registry record last updated 2025-06-10; status last verified 2025-05.
• Results first posted 2025-06-10.
• 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 NCT04406272, titled VB-111 in Surgically Accessible Recurrent/Progressive GBM, as a randomized, double-masked, parallel phase II study sponsored by Dana-Farber Cancer Institute. It enrolled 15 participants and is recorded as terminated. The start date is 2020-08-01, and the primary completion date is 2024-08-01.

The registered primary endpoint was tumor-infiltrating T-cell density, with a planned comparison of Group A against the combined Group B and Group C. The endpoint description states that the analysis was not and will not be performed and that no data were generated. The registry lists progression-free survival at six months and overall survival as secondary outcomes, but their results are not reported.

Group-level serious adverse event, other adverse event, and death counts are recorded. These are descriptive figures and do not establish causation or comparative treatment effects. The reason for termination, analysis populations, missing-data methods, multiplicity approach, and interim analyses are not reported in the registry record.