Open Multi-cohort Study of the First Phase of Safety of a Drug Based on Double Recombinant Vaccinia Virus VV-GMCSF-Lact: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open Multi-cohort Study of the First Phase of Safety of a Drug Based on Double Recombinant Vaccinia Virus VV-GMCSF-Lact (NCT05376527), a na phase 1 study. The primary outcome is Safety Parameters.

2. Clinical Question

These questions fit an early-phase, dose-escalation study, where the main focus is documenting safety across the tested cohorts rather than estimating a treatment effect against a control. The record describes a “3+3” approach for the single-administration Stage 1 and says escalation to the next level occurs if there is no dose-limiting toxicity in the cohort under study. It also describes stopping when the incidence of dose-limiting toxicity in a cohort of 3 participants is 2 or 3. The registry record ends before completing its description of how the maximum tolerated dose would be defined, so that criterion is not reported in the registry record.

The registry records 34 enrolled participants and a completed study status. This enrollment figure is not a count of participants included in every endpoint analysis: endpoint-specific analysis populations are not reported in the registry record. The clinically relevant statistical question is therefore limited to the observed event counts across the listed dose cohorts. Without a control group and without a reported comparative analysis, those counts cannot establish how safety would differ under another treatment or under no study drug.

3. Trial Design

The registry lists this as a Phase 1, open, multi-cohort study. Its stated title concerns the first phase of safety evaluation of VV-GMCSF-Lact, and the official title describes single and multiple administration in patients with recurrent or refractory metastatic breast cancer. The study is marked completed, with a recorded start date of 2022-05-11 and primary completion date of 2025-02-27. Enrollment is 34.

The design is single group, allocation is listed as NA, and masking is listed as NONE. These features mean that the registry does not describe randomized allocation or blinding. The nine reported cohorts distinguish six single-dose cohorts and three multiple-dose cohorts. The single-dose cohort names specify 10^7 PFU, 2 x 10^7 PFU, 4 x 10^7 PFU, 6 x 10^7 PFU, 8 x 10^7 PFU, and 10 x 10^7 PFU. The multiple-dose cohort names specify 6 x 10^7 PFU, 8 x 10^7 PFU, and 10 x 10^7 PFU.

The brief summary says Stage 1 uses one intratumoral administration and a “3+3” design, with dose escalation between levels. Its stated dose range is 1*107 PFU to 10*107 PFU. It describes criteria for dose-limiting toxicity and conditions for escalation or stopping. The summary also refers to a Stage 2, including the primary endpoint timeframe, but the full Stage 2 procedures and cohort rules are not reported in the registry record. The registry record does not provide enough information to reconstruct the complete conduct of either stage.

The study aims include identifying dose-limiting toxicity, describing adverse events, assessing virus pharmacokinetics and antivirus antibodies, and assessing objective response. A secondary outcome is determination of virus concentrations in blood. The primary outcome is safety parameters measured as participant counts. The record lists five outcome measures, but does not provide analysis results for those measures. The sponsor is “Oncostar” LLC.

Because the cohorts have different doses and schedules and there is no randomized control, the cohort comparisons are descriptive. A difference in observed counts between cohorts would not, by itself, isolate a dose effect: cohort size, participant mix, follow-up, and chance variation could also matter. Details on these factors and on any adjustment for them are 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.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Safety Parameters, measured over 90 days from the data of the last treatment (for Stage 1 up to 107 days from participation in the study; for Stage 2 up to 129 days from participation in the study.

The primary endpoint is titled “Safety Parameters” and uses participants as its unit. It is a count endpoint: the number of participants with adverse events, serious adverse events, lethal outcomes, adverse events of grade 3 and higher severity, adverse events leading to withdrawal, adverse events related to investigational product administration, and dose-limiting toxicity. The registry says adverse-event severity was assessed using CTCAE Version 5.0, National Cancer Institute, 2017.

The stated timeframe is 90 days from the date of the last treatment, with Stage 1 follow-up described as up to 107 days from participation in the study and Stage 2 as up to 129 days from participation in the study. These are the endpoint timeframes as recorded; the record does not explain how participants with different exposure or follow-up duration were handled in the analyses.

Counting participants with an event is useful in an early safety study because it identifies how many participants experienced specified safety outcomes during the observation period. It is distinct from counting every event occurrence: one participant can experience more than one event, and a participant count does not describe recurrence or total event burden. The endpoint’s several categories also capture different aspects of safety. Seriousness, severity, relationship to study drug, withdrawal, and dose limitation are not interchangeable definitions.

The registry presents cohort-level serious-event and other-event counts, but does not report the full results for every listed primary-endpoint category. In particular, complete results for grade 3 or higher events, events leading to withdrawal, events related to administration, and dose-limiting toxicity are not reported in the registry record. The endpoint is therefore best interpreted as a planned safety assessment, with only a subset of its stated components quantified in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpretation of an early-phase safety study begins with the estimand: the quantity the analysis is intended to describe. Here, the primary outcome is a count of participants meeting specified safety definitions during a stated timeframe. It is not an average treatment effect against a control, because the registry describes a single-group study and no randomized comparator. The cohort entries give denominators at risk and affected participant counts for serious and other adverse events. They do not provide a model-based estimate of risk difference, relative risk, or treatment effect, and such quantities should not be inferred from the cohort counts.

What does a participant count represent?

A participant count records whether people experienced an outcome under the registry’s definitions; it is not necessarily a count of all episodes. A participant could have several events but contribute once to a participant-level category. Conversely, categories can overlap: one event might be serious, severe, and considered related to treatment. Without a definition of the overlap and separate event listings, category counts cannot be added to obtain a total number of affected people or total events. The registry’s primary outcome lists distinct safety categories, while the presented cohort figures separately distinguish serious events, other events, and deaths.

Seriousness and severity have different meanings in clinical-trial safety reporting. Seriousness concerns the regulatory or clinical consequences used to classify an event, while severity describes intensity. The registry specifies CTCAE Version 5.0 for severity assessment and lists serious adverse events separately. It does not report enough detail to map every serious event to a severity grade, or to determine which events were considered related to study-drug administration.

Why does a single-group design limit comparisons?

In a randomized controlled study, random assignment can support a comparison between groups because treatment assignment is designed to make the groups comparable on average. This study is listed as single group, with allocation NA and masking NONE. Its dose cohorts are not a control group: participants in different cohorts received different dose levels or schedules, and the registry does not describe random assignment among those cohorts. Descriptive contrasts among cohorts may reflect dose, but can also reflect differences in participants, follow-up, or chance. The record does not report an analysis that separates these possibilities.

Open-label conduct can also affect the observation and recording of outcomes that require judgment, although the endpoint includes objective counts as well as clinical classifications. This is a general methodological consideration, not evidence that reporting bias occurred in this study. The registry does not describe blinded event adjudication or other procedures used to reduce judgment-related variation.

How should uncertainty be understood?

In general, a confidence interval expresses a range of values compatible with the observed data under a statistical model and its assumptions. It communicates precision, not certainty that a particular value is true. The registry record does not report confidence intervals for the adverse-event counts. With small cohort sizes, estimates based on the observed counts can be imprecise, and a zero count does not establish absence of risk. This is why raw counts should be read as observations in the enrolled cohorts, rather than as definitive estimates of event frequency in a broader population.

Over-dispersion is a general issue in count data: observed variability can exceed what a simple statistical model expects, for example when outcomes cluster across participants or event rates vary between individuals. If total event counts were modeled, failing to account for such variability could make uncertainty appear too small. The current registry information reports participant counts rather than a model of repeated event totals, and no over-dispersion assessment is reported. This concept is relevant to possible analyses but should not be taken as a description of an analysis performed.

What analysis is actually reported?

The registry record gives cohort-level safety counts and names the primary endpoint, but reports no analysis results for the listed outcomes. It does not report a statistical test, regression model, adjustment set, confidence interval, or prespecified hypothesis test for the safety comparisons. The record does not report whether analyses used all enrolled participants, only treated participants, or another analysis population. Therefore, formal inferential conclusions cannot be reconstructed from the available record.

The brief summary describes a “3+3” dose-escalation approach for Stage 1. This is a cohort-based decision framework: in general, observed dose-limiting toxicities inform whether escalation proceeds or stops. The registry states that escalation occurs if there is no dose-limiting toxicity in the cohort under study and that the study stops if the incidence in a cohort of 3 participants is 2 or 3. It does not report cohort-by-cohort dose-limiting toxicity outcomes or a completed maximum tolerated dose determination. The registry’s description of this rule is not itself evidence that a particular dose was tolerated or selected.

The study summary also describes the assessment of pharmacokinetic parameters, antivirus antibodies, and objective response. Those are distinct outcome domains and would require their own definitions, populations, timepoints, and analyses. Their result values and statistical methods are not reported in the registry record.

Are planning calculations the same as observed evidence?

In general, sample-size planning calculations use assumptions about the effect to detect, variability, significance level, allocation, and analysis method. The record describes an illustrative framework using a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of an observed effect. These are planning assumptions, not a description of the trial’s single-group design. A planning illustration is not an observed power estimate, and sample-size requirements calculated from a hypothetical comparison do not add a control group to this study. The registry does not report a trial sample-size justification or the assumptions used to determine its enrollment target.

For this study, the most defensible statistical reading is descriptive: identify the observed counts and their cohort denominators, distinguish event definitions, and note the absence of comparative inference and uncertainty estimates. That approach avoids overstating what a small, open, multi-cohort safety study can establish.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome includes multiple safety categories: adverse events, serious adverse events, lethal outcomes, adverse events of grade 3 and higher severity, events leading to withdrawal, events related to study-drug administration, and dose-limiting toxicity. The study also lists secondary outcomes and broader aims involving virus concentrations, pharmacokinetics, antivirus antibodies, and objective response. Assessing multiple outcomes can raise a multiplicity question: if many statistical tests are performed, the chance of at least one apparently notable result can increase. In general, trial protocols may address this by specifying a primary comparison, controlling error rates, or treating analyses as exploratory.

The registry record does not report a multiplicity adjustment, a hierarchy among the safety categories, or a prespecified statistical testing plan. It also reports no analysis results or statistical tests for the listed outcomes. Therefore, there is no basis to say that multiplicity was controlled or that a particular finding passed a planned inferential threshold.

Missing-data handling is also not reported in the registry record. The record gives participants at risk for each listed cohort and outcome summary but does not explain exclusions, incomplete follow-up, missing event assessments, or whether participants were analyzed according to treatment received. It does not specify an analysis population for each endpoint. The stated endpoint timeframe includes 90 days from the last treatment, with stage-specific maximum follow-up descriptions; how incomplete observation affected the counts is not reported.

These omissions matter because safety counts depend on both event ascertainment and observation time. A participant with shorter follow-up may have less opportunity for an event to be recorded than a participant followed longer. This is a general issue, not evidence that follow-up was incomplete. The record does not provide participant-level follow-up or missingness information, so the extent and handling of any incomplete data cannot be assessed.

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: uterine polyp (33.3%), cancer complication (25.0%), ileus paralytic (20.0%).

The serious adverse-event entries are counts of affected participants and participants at risk within each cohort. The registry reports 1 among 4 in Cohort 1, 0 among 3 in Cohort 2, 1 among 3 in Cohort 3, 0 among 3 in Cohort 4, 0 among 3 in Cohort 5, 0 among 3 in Cohort 6, 1 among 5 in Cohort 7, 0 among 6 in Cohort 8, and 0 among 4 in Cohort 9. These are not comparative estimates adjusted for cohort differences.

The term “serious” is not synonymous with “grade 3 or higher.” The primary endpoint lists seriousness and severity as separate categories, and says severity was assessed under CTCAE Version 5.0. The cohort summaries do not provide enough detail to identify the severity grade, causal relationship, duration, or outcome of each serious event. The listed serious-event terms and percentages—Uterine polyp, 33.3%; Cancer complication, 25.0%; and Ileus paralytic, 20.0%—are reported without a denominator explanation in the record, so their precise interpretation is limited.

A death is reported in Cohort 1, with none recorded in the other listed cohorts. The registry does not state in these figures that the death was treatment-related. The counts should not be read as evidence of causation. Small cohort sizes also mean that counts can change substantially in relation to the cohort denominator; zero recorded events does not demonstrate zero underlying risk.

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

The record documents a Phase 1 safety study of Double Recombinant Vaccinia Virus VV-GMCSF-Lact involving patients with recurrent or refractory metastatic breast cancer. It identifies nine dose cohorts, including single-dose and multiple-dose schedules, and reports cohort-level counts for serious and other adverse events and deaths. These data describe what was recorded in the trial cohorts; they do not establish a comparative effect relative to another treatment or to no study drug.

All listed cohort entries report at least one participant with an other adverse event, while serious adverse events are recorded in Cohorts 1, 3, and 7. A death is recorded in Cohort 1. Those observations are important safety descriptions, but their interpretation is constrained by the small cohort counts, lack of a control group, and absence of reported uncertainty estimates. They also do not establish whether an event was caused by treatment. Causality and event severity require information beyond the counts presented.

The trial summary describes a dose-escalation process and planned assessment of dose-limiting toxicity, maximum tolerated dose, virus pharmacokinetics, antivirus antibodies, and objective response. The registry record does not report complete results for these aims. In particular, the cohort safety counts alone do not establish the maximum tolerated dose, a dose-response pattern, or an objective response rate.

These data also cannot establish safety beyond the stated study observation period or in populations not described in the record. The number enrolled is not necessarily the number evaluated for each outcome, because endpoint-specific analysis populations are not reported. The available record supports a narrow conclusion: it records the listed safety counts for the named cohorts, while leaving important details about analysis, follow-up, event attribution, and other study outcomes unreported.

No treatment recommendation follows from these descriptive data. Clinical decisions require broader evidence and individual assessment; the statistical interpretation is limited to what the registry records and the precision and design of those observations.

13. Why This Trial Matters Statistically

Early-phase dose-escalation studies pose a distinct statistical challenge: the objective is often to characterize safety across successive exposures while learning which doses warrant further study. A “3+3” rule links observed dose-limiting toxicity to escalation or stopping decisions. That makes careful definitions and complete reporting of dose-limiting events essential. In this record, the design rule is described, but its cohort-by-cohort dose-limiting toxicity results and final dose determination are not reported.

The study illustrates why cohort counts must be read in context. The listed cohorts use different doses or administration schedules, and the registry describes no randomized control. Apparent differences in event counts are therefore descriptive and can reflect factors other than dose. Small cohorts also limit precision. In general, a safety signal may warrant attention even when it is too early or too imprecise to support a stable estimate of event frequency.

Another statistical lesson is the distinction between event definitions. Seriousness, severity, treatment relationship, withdrawal, and dose-limiting toxicity answer different questions. Reporting one category cannot substitute for another. The endpoint lists all of these, but the registry record does not report complete results across the categories. More detailed reporting would be needed to understand how adverse events were classified and how the escalation decisions related to observed toxicities.

The record also shows the boundary between descriptive safety results and broader efficacy or pharmacology claims. The study aims include objective response and virus-related measurements, but those results are not reported in the available registry record. Without a control group, the trial’s design also does not provide a direct comparative treatment-effect estimate. Statistical interpretation should therefore remain focused on the observed cohort safety counts and the limits of their precision.

For clinical researchers, the central issue is not whether a count appears large or small in isolation, but what outcome it represents, who was observed, over what timeframe, and with what uncertainty. The record states some of these elements, while leaving others unreported. Recognizing that boundary is part of responsible interpretation of early-phase evidence.

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 registry record gives a limited account of the analysis. Although it specifies a primary safety endpoint and lists five outcome measures, it does not report analysis results for all endpoint categories. It does not provide confidence intervals, statistical tests, adjusted estimates, or a complete analysis plan. No endpoint-specific analysis populations are identified, so the relationship between enrollment and the denominators used for each outcome cannot be fully evaluated.

The cohort sizes are small, and the design is single group, open-label, and nonrandomized. The dose cohorts are not control groups. Consequently, differences in reported counts cannot be interpreted as causal dose effects or as comparisons with another treatment. The registry does not report participant characteristics by cohort that could help assess comparability.

The serious-event term percentages are listed without an explained denominator in the record. The summaries also do not provide event-level details such as onset, duration, severity grade, treatment relationship, or resolution. The death count is recorded, but the cohort summary does not establish cause. The registry does not report complete results for grade 3 or higher events, events leading to withdrawal, events related to administration, or dose-limiting toxicity.

Follow-up is described using a 90-day period from the last treatment and stage-specific periods of up to 107 days and up to 129 days from participation. The record does not report actual follow-up by participant, the handling of incomplete observation, or missing-data procedures. These details are relevant when comparing event counts across cohorts with different schedules.

The registry describes a Stage 1 escalation rule but does not provide enough information to reconstruct the full Stage 2 design or the completed maximum tolerated dose decision. Results for the stated pharmacokinetic, antibody, and objective-response aims are not reported in the registry record. Accordingly, this interpretation is limited to the recorded cohort safety counts and cannot resolve the study’s other objectives.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open Multi-cohort Study of the First Phase of Safety of a Drug Based on Double Recombinant Vaccinia Virus VV-GMCSF-Lact — NCT05376527.
• Registry record last updated 2026-04-21; status last verified 2026-04.
• Results first posted 2026-04-21.
• 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

NCT05376527 is a completed Phase 1, open, single-group, multi-cohort study sponsored by “Oncostar” LLC. The recorded enrollment is 34. The study evaluated Double Recombinant Vaccinia Virus VV-GMCSF-Lact in patients with recurrent or refractory metastatic breast cancer, using listed cohorts for single and multiple administration at specified dose levels.

The primary outcome is safety parameters, measured as participant counts across adverse-event categories. The registry provides cohort counts for serious and other adverse events and deaths. Serious adverse events are recorded in Cohorts 1, 3, and 7; other adverse events are recorded in every listed cohort; a death is recorded in Cohort 1. These figures are descriptive and do not establish treatment causation or comparative safety.

The registry describes a “3+3” dose-escalation approach for Stage 1. It does not report complete analyses of the primary endpoint, statistical uncertainty estimates, endpoint-specific analysis populations, or results for all stated study aims. The record does not establish a maximum tolerated dose or provide an objective response result.