Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies (NCT05371054), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1: Number of Solicited and/or Non-solicited Non-serious Adverse Events (AE's) With Grade.

2. Clinical Question

3. Trial Design

NCT05371054 was a phase 1/2, non-randomized, unmasked study with a sequential model. It was sponsored by the National Cancer Institute (NCI), enrolled eight participants, and is listed as completed. The registry record lists a start date of 2023-04-05 and a primary completion date of 2024-07-22.

The study concerned VIP152, venetoclax, and prednisone for relapsed or refractory lymphoid malignancies. The phase 1 cohort used dose escalation: VIP152 and venetoclax were given at escalating doses, with prednisone at fixed doses. Its stated objective was to determine the maximum tolerated dose and recommended phase II dose of VIP152 and venetoclax. The phase 2 cohort was described as dose expansion using the recommended phase II dose of VIP152 and venetoclax with fixed-dose prednisone.

The brief description outlines treatment in cycles and describes oral drugs, clinic-administered VIP152, and an injection on a later cycle day. It also lists screening and monitoring procedures, including scans, blood and urine tests, heart-function tests, and a possible bone marrow procedure. The registry record does not report how many participants entered each cohort beyond the adverse-event group figures, nor does it give the treatment duration beyond the endpoint timeframe.

Because allocation was non-randomized and the groups correspond to sequential dose levels, these cohorts do not form a controlled comparison. The registry record does not report a randomization procedure, masking, or a concurrent control group. It also does not report the protocol’s sample-size justification, interim analyses, or a detailed statistical plan. These omissions limit assessment of how the study was planned and how the available observations were intended to support dose selection.

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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: This outcome measure was not done because no participants were enrolled in the phase 2 cohort.

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 Phase 1: Number of Solicited and/or Non-solicited Non-serious Adverse Events (AE's) With Grade, measured over Up to 18 weeks..

The primary endpoint is the number of solicited and/or non-solicited non-serious adverse events with grade. The registry lists the unit as adverse events and the parameter as a number, with assessment over up to 18 weeks. It says grading was assessed by CTCAEv5.0. The record describes a non-serious adverse event as an untoward medical occurrence that does not meet seriousness criteria, and describes Grade 1 as mild, Grade 2 as moderate, Grade 3 as serious, and Grade 4 as life-threatening.

General: adverse-event counts are used to describe the kinds and volume of safety observations during treatment. Grading adds information about severity, while the distinction between serious and non-serious events follows seriousness criteria rather than severity grade alone. Those concepts should not be treated as interchangeable. In a dose-escalation study, safety information is relevant to selecting doses for further study; the stated phase 1 objective was to determine the maximum tolerated dose and recommended phase II dose of VIP152 and venetoclax.

The registry record does not report the number of non-serious adverse events by grade, or a numerical result for this primary endpoint. The adverse-event group summaries report people at risk and affected for serious and other adverse events, but they do not substitute for the missing primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint represent?

The primary endpoint is a count of solicited and/or non-solicited non-serious adverse events with grade. A count records how many events are observed, while a count of affected participants would instead describe how many people experienced an event. Those quantities are not interchangeable: one participant may experience more than one event. The registry record identifies the endpoint unit as adverse events, but does not post its numerical result, detail the counting rules, or state how repeated events were handled.

General: counts are often useful for safety monitoring because they retain information about repeated events. Their interpretation depends on the observation period and on consistent event definitions. The stated timeframe is up to 18 weeks. The registry record does not report whether each participant had the same amount of follow-up for this endpoint or how incomplete follow-up was handled.

Why does grading matter?

The record says adverse events were assessed using CTCAEv5.0 and describes grades from mild through life-threatening. A grade characterizes severity. Seriousness is a separate classification based on criteria about the event; an event may be assessed for both seriousness and grade. The record’s endpoint specifically concerns non-serious events with grade, while the adverse-event summary separately gives serious adverse-event figures. The grade descriptions in the record should not be used to infer that every event of a particular grade was classified as serious.

General: presenting grades can help distinguish mild events from more severe ones, but interpretation also depends on how many events occurred, how many participants were observed, and the completeness of reporting. The primary endpoint’s grade-specific counts are not reported in the registry record, so the posted information does not allow examination of that distribution.

What can the dose groups establish?

The trial is non-randomized and sequential. The phase 1 cohort escalated VIP152 and venetoclax doses, with the stated aim of determining the maximum tolerated dose and recommended phase II dose. The phase 2 cohort was described as expansion at the recommended phase II dose. This structure is intended to support dose exploration, but the record does not report whether the dose-selection objectives were met.

General: dose-escalation observations can inform decisions about which dose to study further, but comparisons across successive cohorts are not equivalent to comparisons between randomized groups. Participants enrolled at different dose levels may differ for reasons other than dose, and changes over time can also complicate direct comparisons. The posted record does not describe adjustment for such differences. Accordingly, group counts should be read descriptively rather than as estimates of a causal dose effect.

How should uncertainty and planning figures be read?

General: an estimate describes an observed pattern, while a confidence interval expresses uncertainty around an estimate under the statistical model used. Wider intervals indicate less precision. The registry record does not report confidence intervals or inferential analyses for the adverse-event groups or the primary endpoint.

Planning illustrations based on an observed effect are not results from this trial and are not observed power. The stated illustration assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record’s trial itself was not a randomized, equal-allocation two-arm comparison. Any such planning figures therefore illustrate hypothetical assumptions rather than the study’s actual design or observed treatment effect. The protocol’s own sample-size justification is not reported in the registry record.

The record lists 12 outcome measures and zero analyses. It does not report the statistical model, estimation procedures, handling of missing data, or analysis populations. Without those details and the endpoint results, readers cannot assess the precision of the primary outcome or reproduce an inferential analysis from the registry summary.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures and zero analyses. It names phase 1 secondary outcomes that include progression-free survival, time to response, duration of response, overall response rate, overall survival, and event-free survival. Numerical results for these outcomes are not reported in the registry record. The record does not describe how many hypotheses were formally tested or whether any adjustment for multiple testing was planned.

General: when a study examines several outcomes, the chance of observing an apparently notable result by chance can increase if each is tested separately. Multiplicity methods address that issue, but the appropriate approach depends on the study’s objectives and analysis plan. No multiplicity strategy is reported in the registry record, so it cannot be determined whether or how this concern was addressed.

Missing-data methods are also not reported. The record does not explain how unavailable assessments, withdrawal, or unequal follow-up were handled for the primary endpoint or secondary outcomes. The endpoint timeframe is up to 18 weeks, but the record does not provide participant-level follow-up or completeness information.

Analysis populations are not specified. The record does not state which participants were included in each outcome analysis or how dose groups were assigned for analysis. It reports eight enrolled participants and adverse-event group counts, but does not provide a participant flow or analysis-specific denominators for the primary endpoint. These omissions limit assessment of whether reported outcomes, if available, would represent all enrolled participants or a defined subset.

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: alanine aminotransferase increased (50.0%), aspartate aminotransferase increased (50.0%), lymph node pain (33.3%).

The serious adverse-event summary lists three dose-level groups. For the group at VIP152 15 mg and venetoclax 600 mg, three participants were at risk and zero were affected by serious adverse events. For the group at VIP152 22.5 mg and venetoclax 600 mg, three were at risk and one was affected. For the group at VIP152 30 mg and venetoclax 600 mg, two were at risk and one was affected. These are descriptive group counts.

The same summary lists other adverse events affecting three of three, three of three, and two of two participants, respectively. It lists deaths of one, two, and one by group. The registry record does not report whether those deaths were related to treatment, their causes, or their timing. A death count should not be interpreted as a count of treatment-related deaths without such information.

Listed serious adverse-event terms include alanine aminotransferase increased and aspartate aminotransferase increased, each at 50.0%, and lymph node pain at 33.3%. Denominators for these percentages are not reported in the registry record. The figures describe reported events and do not establish that treatment caused them. Because the groups are small, non-randomized, and sequential, the counts do not support a reliable comparison of safety across dose levels.

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

The posted results provide limited descriptive information about adverse events in a completed phase 1/2 study with eight participants. The record identifies serious adverse-event counts by dose-level group, reports other adverse events affecting participants in each group, and lists deaths by group. It also names several serious adverse-event terms with percentages. These are observations from the study record, not proof that the regimen caused any particular event.

The primary endpoint was the number of graded non-serious adverse events over up to 18 weeks. Its numerical results are not reported in the registry record. The record also does not report analyses for the listed secondary outcomes. Consequently, the posted information cannot establish the rate or grade distribution of non-serious adverse events, or quantify the secondary clinical outcomes.

General: an early-phase, non-randomized dose-escalation study can describe experience with successive dose levels and inform further investigation. It is not designed as a randomized estimate of comparative effectiveness when it has no randomized control group. The sequential cohorts should not be treated as if they differed only in dose, and the group counts do not demonstrate that one dose is safer or more effective than another.

The record’s phase 1 objective was dose selection, but the posted information does not say whether a maximum tolerated dose or recommended phase II dose was established. Nor does it include enough detail to assess statistical precision, the handling of missing observations, or the attribution of deaths and adverse events. The results therefore support a narrow reading: safety events and deaths were recorded in these small groups, while the primary endpoint values and inferential analyses are unavailable in the registry record.

13. Why This Trial Matters Statistically

This study illustrates a central statistical distinction in early-phase research: observing events within dose cohorts is different from estimating a comparative treatment effect. The registry record describes sequential dose escalation followed by dose expansion, with no randomization and no control group. Its adverse-event summaries can describe what was recorded in each group, but cannot isolate a dose effect from other differences between cohorts.

The distinction between adverse-event counts and affected participants also matters. The primary endpoint is a number of non-serious adverse events with grade, whereas the group summaries report how many participants were at risk and affected for serious and other adverse events. Those measures answer different questions. The primary endpoint’s numerical results are not reported, so the participant-level safety summaries do not fill that gap.

General: small studies are often valuable for identifying practical questions and describing early experience, but estimates from small groups are typically imprecise. This is especially important when counts are presented by several dose levels and there is no concurrent randomized comparison. A descriptive safety pattern can motivate further study, but it should not be mistaken for a stable estimate of event frequency or a causal treatment comparison.

The record also shows why registry completeness affects statistical interpretation. It lists 12 outcome measures and zero analyses, yet does not post the primary endpoint result, analysis populations, missing-data approach, or multiplicity plan. These omissions prevent a full assessment of precision and analytic choices. Clear endpoint results and methods are essential for distinguishing what was observed from what can be inferred.

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 reports eight enrolled participants, with adverse-event summaries divided among three sequential dose levels. The groups are small, and the non-randomized design does not support like-for-like comparisons across them. The record does not provide a randomized control group or a basis for attributing between-group differences to dose alone.

The primary endpoint is named and described, but its numerical results are not reported in the registry record. The record also lists 12 outcome measures and zero analyses. Although several secondary outcomes are named, their results and the analysis methods are not reported. The protocol’s sample-size justification, interim analyses, and detailed statistical plan are not reported in the registry record.

Additional safety detail is unavailable. The record does not report causes or treatment attribution for deaths, event timing, participant-level follow-up, or denominators for the listed serious adverse-event term percentages. It does not specify analysis populations or how missing assessments and incomplete follow-up were handled. The timeframe for the primary endpoint is up to 18 weeks, but completeness of that observation period is not described.

The brief treatment description ends before specifying the full treatment duration. The registry record therefore does not establish how long participants actually received treatment or were observed for all outcomes. These limitations mean the posted counts should be interpreted narrowly as descriptive registry information, without drawing conclusions about comparative safety, causation, or outcomes not reported.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of VIP152, Venetoclax, and Prednisone (VVIP) in Relapsed/Refractory Lymphoid Malignancies — NCT05371054.
• Registry record last updated 2026-02-23; status last verified 2026-02.
• Results first posted 2025-04-08.
• 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

NCT05371054 is a completed, non-randomized, unmasked phase 1/2 study of VIP152, venetoclax, and prednisone in relapsed or refractory lymphoid malignancies. The sequential study enrolled eight participants. Phase 1 used dose escalation to determine the maximum tolerated dose and recommended phase II dose; phase 2 was described as dose expansion at the recommended phase II dose.

The primary endpoint was the number of graded non-serious adverse events over up to 18 weeks. The registry record does not report its numerical results. It lists serious and other adverse-event summaries and deaths by dose-level group, but does not report cause or treatment attribution for deaths. Twelve outcome measures and zero analyses are listed. The record does not report a randomized comparison, detailed statistical plan, missing-data approach, analysis populations, or results for the named secondary outcomes.