Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors (NCT02478320), a na phase 2 study. The primary outcome is Response Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group basket trial of ilorasertib (ABT-348) in patients with CDKN2A-deficient advanced solid cancers. The sponsor was M.D. Anderson Cancer Center. The study record lists enrollment of 12 and a status of terminated. It gives a study start date of 2016-08-05 and a primary completion date of 2022-05-12. The reason for termination is not reported in the registry record.

The study was unmasked, and allocation was listed as not applicable. With no randomized comparator, the design is not a controlled treatment comparison. A response observed among participants would describe what occurred in this study group; without a concurrent control group, it cannot by itself separate the effect of treatment from other explanations for the outcome.

The intervention was ilorasertib, administered by mouth at 200 mg twice daily on Days 1, 8, and 15 of each 28-day cycle. The arm description includes Part 1 and a Part 2 tumor-specific expansion. The safety record lists 9 participants at risk in Part 1 and 0 at risk in Part 2. These safety denominators should not be treated as a reported primary endpoint analysis population.

The record identifies safety and tolerability and pharmacodynamic activity as secondary outcomes. It does not report the detailed statistical plan, the reason for the study’s termination, or a primary response analysis. A sample-size justification for the trial’s own design 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.

Before assignment: Some patients who consented to join the study were ultimately not treated either because of screen failure or imminent loss of drug supply

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients with tumors harboring CDKN2A deletion or mutation

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Part 2 Tumor-specific expansion (trial was terminated before this part was reached)

6. Primary Endpoint

The registry lists the primary outcome as Response Rate, measured over through study completion, maximum 18 months.

The primary endpoint is titled “Response Rate” and is expressed as a count of participants. It concerns partial or complete response to ilorasertib among patients whose tumors had CDKN2A deletion or mutation. The specified observation period is through study completion, with a maximum of 18 months.

In general, a response endpoint is used to describe whether a participant’s disease meets a defined response category during the specified assessment period. A count indicates how many participants had the event; a rate additionally requires a defined denominator. Interpreting such an outcome also depends on how response was assessed, when assessments occurred, and how missing or unevaluable assessments were handled. Those details are not reported in the registry record.

The record does not give the number of partial or complete responses, an endpoint denominator, or a response-rate estimate. Enrollment of 12 is not itself a response count and should not be substituted for the analyzed population without a reported analysis definition. As a result, the registry record identifies the outcome of interest but does not provide a posted result for it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who received the study intervention. It can estimate the observed frequency of an outcome in that group if both the event count and the analysis denominator are reported. It does not directly estimate the difference between treatment and control, because there is no concurrent control group in this design. This study lists allocation as not applicable, masking as none, and a single-group model.

The design is relevant when reading the endpoint because a partial or complete response in a participant is an observed outcome, not a controlled estimate of what would have happened under another treatment. Without random assignment to a comparator, differences in patient characteristics, disease course, or other care can complicate causal interpretation. These are general limitations of uncontrolled comparisons, not findings about a particular participant in this study.

How should a participant count be read?

The primary endpoint is a count of participants with partial or complete response. A count and a rate are related but not interchangeable: a rate requires both a numerator and a defined denominator. The registry record states enrollment of 12, but it does not report the response count, the denominator used for endpoint analysis, or the rules for determining which participants were evaluable. It is therefore not possible to reconstruct an endpoint result from the enrollment figure.

In general, the analysis population may differ from the enrolled population if eligibility, treatment exposure, assessment availability, or other rules define who contributes to an endpoint. The applicable population and handling rules are not reported in the registry record. The stated timeframe is through study completion, with a maximum of 18 months; the assessment schedule and the handling of participants without a response assessment are not reported.

What would uncertainty measures add?

In general, a confidence interval describes a range of values compatible with the data under a statistical model and indicates the precision of an estimate. For a response outcome, the interval would help convey uncertainty around the observed response frequency, rather than treating the point estimate as exact. Its interpretation would depend on the event count, denominator, and method used to construct the interval.

No primary response estimate or confidence interval is reported in the registry record. No interval should be inferred from enrollment alone. A small or otherwise limited dataset can yield imprecise estimates, but the record does not supply the response data needed to quantify that uncertainty for this endpoint.

What does a planning illustration mean?

In general, sample-size planning asks how many participants would be needed under specified assumptions to detect a chosen effect with a stated probability, often called power. A planning calculation is conditional on its assumptions; it is not evidence that the study had that probability of detecting an effect after the trial was completed. It is also not an observed outcome.

The planning assumptions described for this analysis use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. Those assumptions describe an illustration rather than the design of this single-group study. The record does not report the trial’s own sample-size justification, and the planning assumptions do not turn this study into a two-arm randomized comparison. Any such illustration should not be described as observed power.

Why can event counts differ from event rates?

In general, the count of participants with an event and the number of events are distinct quantities. One participant may experience more than one event, while a participant-level count usually records whether the participant had at least one event in a category. The safety record reports participants at risk and participants affected, but it does not explain whether multiple occurrences or overlapping event terms are counted separately in every listing. The listed serious adverse event terms and percentages should therefore be read as the registry presents them, without assuming that they represent mutually exclusive groups.

For count outcomes, the statistical approach should match the question and data structure. Binary outcomes such as having or not having a response are often analyzed as proportions; repeated events may require methods that account for within-participant dependence. These are general methodological considerations. The registry record does not report the analysis method used for the primary endpoint or the safety outcomes.

What can be concluded from the reported methods?

The record supports a description of the trial structure, intervention schedule, endpoint definition, enrollment, and selected safety counts. It does not provide the primary response analysis, a confidence interval, a detailed statistical plan, or analysis-population rules. Statistical interpretation should stay within those boundaries: no unreported endpoint result or treatment comparison can be recovered from the design description alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and identifies safety and tolerability and pharmacodynamic activity among the secondary outcomes. The primary outcome is response rate. When a study evaluates multiple outcomes, there may be more than one opportunity to observe a noteworthy result. In general, multiplicity methods can control the chance of false-positive conclusions across a prespecified family of tests, or investigators may identify one outcome as primary and treat others as supportive or exploratory. The statistical plan and any multiplicity adjustment are not reported in the registry record.

The record also does not report a primary endpoint analysis or an analysis population. It is not possible to determine whether the response endpoint was evaluated in all enrolled participants, only in participants meeting a particular eligibility or assessment rule, or in another defined group. Enrollment of 12 should not be assumed to be the denominator for a response rate.

Missing-data procedures are not reported in the registry record. In general, absent response assessments can affect an endpoint if participants without assessments are excluded, classified as nonresponders, or handled through another method. These approaches can yield different interpretations, so the rule should be stated before assessing a reported response estimate. No such rule or estimate is available in this record.

The trial is listed as terminated, but the record does not state the reason or explain whether the termination affected outcome collection. The timing and completeness of outcome assessments, interim analyses, and any changes to the analysis plan are not reported in the registry record. Without those details, the outcome reporting cannot be assessed for the impact of missing observations, selective reporting, or changes made during the study.

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: sepsis (11.1%), vomiting (11.1%), uncontrolled pain (11.1%), hypertension (11.1%), cervical stenosis (11.1%).

For Part 1, the registry record reports 9 participants at risk for serious adverse events and 5 affected. For other adverse events, it reports 9 at risk and 7 affected. The Part 2 tumor-specific expansion safety group has 0 at risk and 0 affected in both categories. The record also lists 1 death in Part 1.

The listed serious adverse event terms are sepsis, vomiting, uncontrolled pain, hypertension, and cervical stenosis, each reported at 11.1%. These are registry-listed frequencies. The record does not give further details about event timing, severity grading, recurrence, overlap among terms, or attribution to treatment. The percentage listings should not be treated as proof that the events were caused by ilorasertib.

In general, safety counts describe what was recorded in a group; they do not establish comparative risk without an appropriate comparison and sufficient outcome detail. A death count likewise does not by itself identify cause or treatment relationship. The registry record does not report the cause of the death or whether investigators considered it related to treatment. The figures are descriptive, and the absence of a listed event in a group with 0 at risk does not provide a meaningful comparative safety estimate.

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

The record establishes that a phase II study of ilorasertib in patients with CDKN2A-deficient advanced solid cancers was conducted as a single-group, unmasked study and is listed as terminated. It reports 12 participants enrolled and describes a primary outcome of partial or complete response through study completion, up to 18 months. It also gives selected safety counts for Part 1 and lists serious adverse event terms and frequencies.

It does not report the primary response count, a response-rate estimate, or an uncertainty interval. Consequently, the registry record does not show how many participants had a partial or complete response, nor how precisely any response frequency was estimated. The treatment schedule and study objective cannot substitute for those missing outcome results.

The study also does not provide a randomized control comparison. Even if a response result were available, a single-group observation would not establish how outcomes would have differed under another treatment or no study treatment. General factors such as participant selection and the natural course of disease can affect outcomes in uncontrolled studies.

The reported adverse event counts and death are descriptive. The registry record does not establish causation, provide a comparison group, or report the reason for study termination. The listed safety figures therefore do not, on their own, show whether an event was attributable to treatment or how its frequency compares with another group.

The appropriate conclusion is limited: the record documents the study design, the intended primary outcome, enrollment, and selected safety observations, but it does not report the primary efficacy result. The reason for termination and important analysis details are also not reported in the registry record. No conclusion about treatment effect or comparative safety should be drawn beyond these documented details.

13. Why This Trial Matters Statistically

This trial is statistically notable because its central question concerns a defined molecular subgroup, while its design is a single-group phase II study. A focused population can make a study question specific, but the design still determines what can be inferred. Without a randomized comparator, the study can describe outcomes in the treated group but cannot directly estimate a treatment-versus-control contrast.

The primary endpoint is a participant count for partial or complete response, which is a clinically interpretable type of binary outcome. To assess it statistically, readers need the response count, the denominator, and a measure of uncertainty. The registry record does not report those primary endpoint results. This illustrates why a stated endpoint and enrollment total are not enough to judge the magnitude or precision of an observed effect.

The record also makes the distinction between outcome reporting and planning important. A planning illustration based on an observed effect is conditional on assumptions and is not an observed power calculation. It cannot replace an analysis of the trial’s own endpoint, particularly when the response result is not reported. A sample-size justification for this trial is not reported in the registry record.

Finally, the safety figures require careful interpretation. Participant counts, percentages attached to event terms, and a death count describe different aspects of safety reporting and do not establish causation. The study’s terminated status is relevant context, but without a stated reason it should not be used to speculate about efficacy, safety, or feasibility. Together, these points show why design, endpoint reporting, analysis transparency, and uncertainty must be considered separately.

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 primary limitation for interpreting efficacy is that the registry record does not report a response count, response-rate estimate, or confidence interval. The endpoint’s definition and timeframe are stated, but the denominator and analysis population are not. Enrollment of 12 does not resolve those gaps.

The single-group, unmasked design has no randomized control comparison. It therefore cannot support a direct estimate of the difference between ilorasertib and a comparator. This limitation applies independently of whether a response was observed in individual participants.

The record is marked terminated, but its reason for termination is not reported in the registry record. It is also not reported whether termination affected the completion of outcome assessments or the availability of endpoint data. No inference about the reason or consequences of termination is justified from the status alone.

Important statistical details are absent: the sample-size justification for the trial, the statistical analysis plan, analysis-population definitions, missing-data procedures, multiplicity handling, and any interim analyses are not reported in the registry record. Without these details, readers cannot evaluate how endpoint analyses were specified or how incomplete assessments may have been handled.

Safety interpretation is also constrained. The record gives selected counts and serious adverse event terms, but does not report event-level detail, treatment attribution, the cause of the reported death, or a comparator group. The Part 2 safety record lists 0 participants at risk, limiting what that group’s safety entries can establish. These limitations are specific to the information and design documented for this study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors — NCT02478320.
• Registry record last updated 2023-07-17; status last verified 2023-07.
• Results first posted 2023-07-17.
• 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

NCT02478320 is a phase II, single-group, unmasked study of ilorasertib (ABT-348) in patients with CDKN2A-deficient advanced solid cancers, sponsored by M.D. Anderson Cancer Center. The record lists 12 participants enrolled, a start date of 2016-08-05, a primary completion date of 2022-05-12, and a terminated status.

The primary endpoint was a count of participants with partial or complete response through study completion, up to 18 months. The registry record does not report a primary response result or its analysis. Part 1 safety reporting lists 9 participants at risk for serious adverse events, 5 affected, 9 at risk for other adverse events, 7 affected, and 1 death. The reason for termination and key statistical analysis details are not reported in the registry record.