Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma (NCT02490800), a randomized phase 1, phase 2 study. The primary outcome is Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin.

2. Clinical Question

3. Trial Design

This completed study combined Phase 1 dose escalation with a Phase 2a dose expansion. The registry describes it as an open-label study of oral lisavanbulin in adults with advanced solid tumors and in adults with recurrent or progressive glioblastoma or high-grade glioma. The study started on 2015-05-20, and primary completion is listed as 2022-09-30. Total enrollment was 72.

The Phase 1 portion enrolled patients in two disease groups: advanced or recurrent solid tumors, and recurrent or progressive glioblastoma or high-grade glioma. Its arm description specifies an accelerated 3+3 titration design. The Phase 2a description specifies a Simon's two-stage design for patients with recurrent and EB1-positive glioblastoma. The listed interventions are the Phase 1 dose-escalation portion and the Phase 2a expansion portion, both involving lisavanbulin.

The registry metadata lists randomized allocation, no masking, and a parallel model. However, the record does not explain how randomization related to the dose-escalation and expansion portions, identify the randomization procedure, or describe a distinct untreated or active comparator. Those metadata alone do not establish that the posted groups form a randomized treatment comparison. The study is explicitly open-label, so masking was not used.

The Phase 1 primary endpoint concerns the maximum tolerated dose during the first 28-day cycle, with dose-limiting toxicities graded under CTCAE. The Phase 2a outcomes include progression-free survival and progression-free survival at 6 months, as well as safety and other outcomes. Details of the full protocol, the sample-size justification, and the relationship between all analysis populations 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.

Before assignment: In the Phase 1 study, a total of 29 screening-failures occurred. Thus a total of 72 patients with advanced solid tumors, recurrent or progressive glioblastoma (GBM) or high-grade glioma (HGG) were enrolled in this Phase 1 and Phase 2a study.

Only the first 6 of 13 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: MTD population: All patients from the safety set who met the following during the first 28-day treatment Cycle 1: * Received at least one dose of lisavanbulin and had experienced a DLT * Received at least 24 of the scheduled 28 doses for daily lisavanbulin administration, were not experiencing a DLT, had been observed for ≥ 28 days following the first dose, and had been evaluated for safety

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 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1: Maximum Tolerated Dose (MTD) of Daily Oral Lisavanbulin, measured over During first 28 day cycle.

The primary endpoint is the Phase 1 maximum tolerated dose of daily oral lisavanbulin, measured in mg. Its timeframe is the first 28-day treatment cycle. The registry describes the endpoint as based on dose-limiting toxicities graded according to CTCAE and assessed in an MTD-determining population. This makes the endpoint a dose-finding and tolerability measure, rather than a measure of tumor response or survival.

Dose escalation studies use dose-limiting toxicity information to identify a dose level for further study. In general, this kind of endpoint helps describe the balance between increasing exposure and treatment-limiting toxicity in the study population. It is not a randomized comparison of lisavanbulin against another treatment, and it does not by itself establish how a dose performs on later clinical outcomes.

The registry reports a value of 16 mg for the Phase 1 advanced or recurrent solid-tumor group, whose listed sample size is 23, and a value of 30 mg for the Phase 1 recurrent or progressive glioblastoma or high-grade glioma group, whose listed sample size is 24. No dispersion measure, confidence interval, or formal comparison accompanies these values. The MTD population description is partly truncated in the registry record, so its complete eligibility rules cannot be reconstructed from the posted text. The endpoint therefore has to be interpreted as the recorded dose-finding result, with its population detail and uncertainty incompletely documented.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted outcomes use different statistical forms, so their numbers answer different questions. The primary endpoint is a dose value in mg. The Phase 2a progression-free survival result at 6 months is a percentage with a 95% confidence interval, while the comparison between FAP and EEP is expressed through a risk difference, relative measures, and an unadjusted p-value. These methods should not be conflated: the dose-finding result is not a treatment-effect estimate, and the Phase 2a percentage is not itself a comparison against an external control.

What does a confidence interval convey?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the analysis. A wider interval indicates less precision than a narrower one. The Phase 2a 95% confidence intervals extend from 11.8% to 53.1% for FAP and from 16.3% to 67.9% for EEP. Their width indicates that the posted percentages are imprecise estimates. The interval does not capture every source of uncertainty: it does not, for example, resolve questions about population definitions, missing observations, or whether the analysis plan was followed.

The comparison interval for the risk difference is also reported, but its endpoints are not needed to understand the main message: it includes no difference. The unadjusted p-value is 0.47. In general, a p-value measures how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. Because this result is unadjusted and secondary, it should be treated as exploratory rather than as a definitive conclusion about the populations.

Why distinguish the analysis populations?

The registry gives separate progression-free survival percentages for FAP and EEP. In general, analysis populations can differ in which participants or observations they include, and that difference can change an estimate. The record does not define these two labels or state how participants entered each population. It is therefore not possible to determine from the registry record whether the distinction reflects eligibility, evaluability, follow-up, or another rule. The percentages should be read as belonging to the named populations, not as two versions of the same estimate with known membership rules.

The FAP and EEP results are not an ordinary randomized comparison simply because the study metadata lists randomized allocation. The registry does not describe randomization between these populations, nor does it establish that they are exchangeable. A numerical difference between their estimates should not be interpreted as a causal treatment effect without the design and analysis details needed to support that interpretation.

What does the planning illustration mean?

The planning illustration uses the observed effect as its starting point and considers detecting a stated fraction of that effect. It assumes a two-sided significance level of 0.05, equal allocation, and a normal approximation. For 100% of the observed effect, it gives 228 participants per arm for 80% power and 305 participants per arm for 90% power. For 75% of the observed effect, the corresponding values are 400 and 535 participants per arm. For 50% of the observed effect, they are 885 and 1,184 participants per arm.

These are planning illustrations, not the study's enrollment target, not a record of the design's sample-size justification, and not observed power. They depend on assumptions about the effect to detect and the statistical method. The registry record does not report that the trial was designed around these values. The illustration cannot show what the study would have found under a different sample size, nor does it establish that the study was adequately powered for its actual objectives.

How should dose finding be understood?

In general, a dose-escalation design uses observed toxicity information at successive dose levels to guide which doses are explored. The registry describes an accelerated 3+3 titration design for Phase 1 and defines the MTD in relation to dose-limiting toxicities during the first 28-day cycle. The reported endpoint values therefore summarize a dose-finding decision, rather than an estimate with the usual confidence interval for a treatment effect. The registry record does not report the detailed decision rules, the dose-by-dose primary endpoint data, or the method used to determine the final value. It is not possible to independently assess the dose-finding procedure from the posted endpoint values alone.

The primary population description specifies that participants had to meet conditions related to treatment and dose-limiting toxicity during Cycle 1, but the text is truncated. The complete membership rules are not reported in the registry record. This matters because the result applies to the defined MTD-determining population, and a reader cannot fully establish who was eligible for that analysis from the incomplete description.

What is the role of secondary outcomes?

Secondary outcomes include safety, pharmacokinetic measures such as Cmax, Tmax, and AUC, and tumor-related measures such as best objective response, objective response rate, progression-free survival, and progression-free survival at 6 months. In general, secondary analyses can add context about exposure, safety, or outcomes beyond the primary question. They also involve multiple opportunities to observe a notable result. The registry does not report an adjustment for multiplicity or a hierarchy that would control the interpretation of these findings. Unadjusted secondary p-values should therefore be viewed cautiously, especially when the outcomes are not the primary endpoint.

There are 12 outcome measures listed and 9 secondary outcomes posted, while no analyses are listed as reported analyses. The distinction between posted outcome values and reported analyses is important: a numerical estimate can be available without a complete account of the statistical model, analysis population, or prespecified testing strategy. In general, statistical estimates depend on those choices. The registry record does not report enough detail to reconstruct all of them.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity strategy for the secondary outcomes. This leaves unclear whether any outcomes were prioritized for formal testing, whether testing was conducted in a sequence, or whether an adjustment was used to account for multiple comparisons. In general, when multiple outcomes are examined, a result that appears notable can arise by chance even if there is no underlying effect. Unadjusted secondary analyses should therefore be interpreted as exploratory unless the design and testing plan support a stronger conclusion.

Missing-data methods are not reported in the registry record. The record does not specify how unavailable outcome measurements, loss to follow-up, or incomplete assessments were handled for the primary endpoint or the Phase 2a progression-free survival analysis. It also does not report whether sensitivity analyses were conducted. These omissions matter because missing observations can affect the population contributing to an estimate and can influence its interpretation.

The registry lists FAP and EEP populations for the Phase 2a progression-free survival result, but does not define those labels. The primary MTD population description is also truncated after its eligibility conditions begin. Thus, the complete analysis-population rules are not available for either endpoint. The listed enrollment of 72 should not be assumed to be the denominator for every analysis; the posted endpoint results give their own group sample sizes, and the relationship between enrollment and each analysis population is not fully described.

The record reports no analyses as reported analyses. It does not provide a statistical analysis plan, a complete account of interim analyses, or the rationale for the sample size. The Phase 1 arm description names an accelerated 3+3 titration design, and the Phase 2a description names a Simon's two-stage design, but detailed operating rules and decision criteria are not reported in the registry record. These gaps limit evaluation of prespecification, population selection, and the potential for selective emphasis among outcomes. They do not establish that such practices occurred; they mean that the available record does not resolve those questions.

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: gait disturbance (66.7%), confusional state (66.7%), ataxia (33.3%), dysarthria (33.3%), partial seizures (33.3%).

The safety results are organized by dose and disease group, with separate counts for serious adverse events, other adverse events, and deaths. The number at risk differs among the listed groups, so the raw counts should be read alongside each group's denominator. These are group-level descriptions, not an overall rate for all participants. For example, the Phase 2a recurrent glioblastoma group lists 18 participants at risk for serious adverse events and 8 affected; it lists 18 at risk for other adverse events and 18 affected, with 7 deaths recorded. The registry does not provide enough context in these fields to attribute those deaths to lisavanbulin.

The serious-event terms listed include gait disturbance and confusional state at 66.7%, and ataxia, dysarthria, partial seizures, and dyspnoea at 33.3%. These percentages are presented as serious-event terms, but the registry record does not provide their denominators or detailed rules for how events were selected for this list. They should not be treated as percentages of all enrolled participants without that context.

In general, adverse-event counts describe events recorded during a study and do not by themselves establish causation. Differences between dose groups also cannot be interpreted as dose effects without considering group size, participant characteristics, follow-up, and the study's safety definitions. The record lists a secondary outcome for CTCAE Grade 3-4 TEAEs, but the posted safety fields are not a substitute for a complete analysis of that outcome. Detailed attribution and analysis methods are not reported in the registry record.

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

The primary result describes the dose-finding endpoint recorded for each Phase 1 disease group: 16 mg for advanced or recurrent solid tumors and 30 mg for recurrent or progressive glioblastoma or high-grade glioma. It is a result about maximum tolerated dose during the first 28-day treatment cycle, not a measure of tumor response, long-term tolerability, or comparative benefit. No uncertainty interval is reported for these values, and the MTD population definition is incomplete in the registry record.

The Phase 2a progression-free survival percentages at 6 months provide descriptive estimates for the FAP and EEP populations. Their confidence intervals are broad, and the unadjusted comparison has p = 0.47. The registry does not define the populations or describe a comparator in the arm descriptions that would support a conventional treatment-versus-control interpretation. These results therefore do not establish that the populations differ or that they are equivalent.

In general, a statistical result is bounded by its design, endpoint, analysis population, and uncertainty. A dose-finding result should not be interpreted as proof of efficacy. A secondary endpoint should not be treated as confirmatory when its analysis plan and multiplicity strategy are not reported. A non-significant p-value does not prove that there is no difference, just as a numerical difference between percentages does not by itself establish a meaningful or causal effect.

The posted findings also do not provide a complete picture of missing observations, long-term safety, or the details of all outcome analyses. The record lists the study as completed, but completion status does not resolve these statistical limitations. The results are best understood as registry-reported dose-finding, safety, and exploratory outcome information for this particular study, rather than as a stand-alone basis for conclusions about treatment effectiveness or comparisons with other options.

13. Why This Trial Matters Statistically

This study illustrates a statistical feature common to early-phase research: its central question can be about dose and tolerability rather than comparative efficacy. The primary endpoint is the maximum tolerated dose during the first 28-day treatment cycle, assessed through dose-limiting toxicities. That endpoint requires a different interpretation from a response percentage or a time-to-event outcome. Separating those questions helps prevent a dose-finding result from being mistaken for evidence of clinical benefit.

The design also combines dose escalation and expansion, with different design descriptions for the two portions. The registry names an accelerated 3+3 titration design for Phase 1 and a Simon's two-stage design for Phase 2a. These details make the study statistically distinctive, but the available record does not report the full decision rules or analysis plan. This illustrates why a design label alone is not enough to assess operating characteristics or reproduce an analysis.

The posted Phase 2a progression-free survival estimates show how uncertainty can remain substantial even when percentages are reported to one decimal place. Their confidence intervals are broad, and the unadjusted comparison does not provide clear statistical evidence of a difference. The named populations are not defined in the record, limiting interpretation further. Reading the estimates together with their uncertainty and population labels is more informative than focusing on the percentages alone.

Finally, the outcome set spans dose finding, safety, pharmacokinetics, response, and progression-free survival. That range can provide useful descriptive context, but it also creates a multiplicity question. Without a reported testing hierarchy or adjustment, secondary findings should not be given the same confirmatory weight as a prespecified primary result. The study is a useful example of why endpoint purpose, analysis population, uncertainty, and reporting completeness all matter when interpreting clinical-trial statistics.

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 leaves important details unavailable for interpreting the reported outcomes. The description of the MTD-determining population is truncated, and the FAP and EEP labels used for the Phase 2a progression-free survival result are not defined. As a result, it is not possible to determine fully who contributed to each analysis or how eligibility and evaluability rules shaped the estimates.

The primary MTD values are presented without a confidence interval or other dispersion measure. The record also does not report dose-by-dose primary endpoint results or the detailed rules used to select the reported MTD. This limits independent assessment of the precision and derivation of the dose-finding result. The posted sample sizes for the primary groups do not, on their own, explain how participants were distributed across dose levels.

The registry lists randomized allocation, but does not explain how randomization was applied to the described dose-escalation and expansion portions. The arm descriptions do not identify a separate control treatment. Consequently, the metadata should not be taken as evidence that the Phase 2a populations form a randomized treatment comparison. The lack of masking is reported, while other practical details about conduct are not.

For secondary outcomes, the record does not report a multiplicity adjustment, missing-data methods, or a statistical analysis plan. It lists 12 outcome measures and 9 secondary outcomes posted, but no analyses as reported analyses. The adverse-event group counts have different denominators, and the serious-event term percentages are not accompanied by denominators in the record. These reporting gaps restrict synthesis across outcomes and groups. They do not show that an analysis was necessarily inappropriate; they limit what can be verified from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 1/2a Study of Oral BAL101553 in Adult Patients With Solid Tumors or Glioblastoma or High-grade Glioma — NCT02490800.
• Registry record last updated 2024-06-26; status last verified 2024-06.
• Results first posted 2024-06-26.
• 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

NCT02490800 is a completed, open-label Phase 1/2a study of oral lisavanbulin in adults with advanced solid tumors or recurrent or progressive glioblastoma or high-grade glioma. Total enrollment was 72. The study began on 2015-05-20, with primary completion listed as 2022-09-30. The registry describes Phase 1 dose escalation and Phase 2a dose expansion.

The Phase 1 primary endpoint was maximum tolerated dose during the first 28-day cycle. The posted values are 16 mg for the advanced or recurrent solid-tumor group and 30 mg for the recurrent or progressive glioblastoma or high-grade glioma group. Phase 2a progression-free survival at 6 months is reported for FAP and EEP populations, with broad confidence intervals and an unadjusted comparison of p = 0.47.

The record also contains safety and other secondary outcomes, but does not report a complete analysis plan, multiplicity strategy, or missing-data methods. Population definitions are incomplete or absent for some results. The posted findings should be interpreted in light of those limits and the study's dose-finding purpose.