p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246 (NCT03268382), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

The study’s stated purpose was to make a preliminary assessment of efficacy for APR-246 combined with PLD in this population. The registry also describes aims to assess safety, evaluate potential biomarkers, and assess biological activity in tumor and surrogate tissues. Those aims do not make the study a controlled test of the regimen against another treatment: no comparator arm is listed.

Overall response rate is based on participants categorized as having complete or partial response under the stated RECIST criteria. The record defines complete response as disappearance of all target lesions and partial response as a decrease of at least 30% in the sum of the longest diameters of target lesions. However, it gives no response count, response proportion, or uncertainty interval. The enrolled count alone cannot establish how many participants were assessed for response or what responses were recorded.

The registry describes the study as Phase II and says it will enroll at least 25 evaluable patients. It reports 36 patients enrolled, but the number evaluable for the primary endpoint is not reported in the registry record. Thus, the clinical question is identifiable, but the posted record does not provide the primary outcome needed to answer it.

3. Trial Design

This is a completed Phase II study with a single-group model. The registry lists 36 enrolled patients and identifies APR-246 and pegylated liposomal doxorubicin hydrochloride (PLD) as the interventions. The population of interest is patients with platinum-resistant recurrent HGSOC with mutated TP53. The record gives a start date of 2017-07-31 and a primary completion date of 2019-07-10.

The allocation field is NA and masking is listed as none. No separate comparator group is described. Although the study is characterized as single-group, the registry also distinguishes dose cohorts: 28 patients were in the main-study 4.5g/6hr cohort, while 8 were in sub-study cohorts. The primary outcome description specifies 3 patients in the 4.5g/3hr cohort and 2 in the 4.5g/4hr cohort, then ends before completing its account of the remaining sub-study participants. The adverse-event listing also names a 3.7g/4hr cohort. These dose groups do not provide a randomized or otherwise equivalent control comparison.

The primary outcome is overall response rate, assessed by MRI using RECIST v1.0 criteria for target lesions over up to 18 months. The registry lists treatment-emergent adverse events with the combined regimen as a secondary outcome. It also describes biomarker and biological-activity aims in the study summary. The number of outcome measures is listed as 2, but detailed results for the primary response outcome are not reported in the registry record.

The registry status is completed. Completion describes the study’s recorded status; it does not itself indicate that the primary outcome was met or that a treatment effect was established. Details such as a formal statistical analysis plan, the rationale for the planned enrollment, and procedures for assigning participants among dose cohorts are not reported in the registry record. Without a control group, comparisons among the dose cohorts should not be treated as randomized comparisons of efficacy or safety.

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: A total of 36 patients were enrolled in this Phase II study. Of the 36 patients, 28 patients were in the main study, 4.5g/6hr dose cohort; 8 patients were in the sub-study as follows: 3 patients were in the 4.5g/3hr dose cohort; 2 patients were in the 4.5g/4hr dose cohort and 3 patients were in the 3.7g/4hr dose cohort. The 23 Efficacy Evaluable Patients from the Main Study (APR-246 (4.5g/6hr) + PLD) are part of the analysis reported below.

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: Patients with Pt-resistant HGSOC with TP53 mutation.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR), measured over Up to 18 months.

The primary endpoint is overall response rate (ORR), expressed as a count of participants meeting the response definition. The registry specifies complete response (CR) or partial response (PR) under RECIST v1.0 for target lesions assessed by MRI, with an assessment timeframe of up to 18 months. It defines CR as disappearance of all target lesions and PR as at least a 30% decrease in the sum of the longest diameters of target lesions. The record defines overall response as CR plus PR.

In general, ORR is used as a tumor-response measure because it classifies whether participants meet specified imaging criteria during a stated assessment period. It is a binary outcome at the participant level: a participant either meets the response definition or does not. This makes the endpoint straightforward to describe as a count and, when a denominator is available, as a proportion. A proportion and its uncertainty can help readers judge how precisely the response frequency has been estimated. The registry record does not report the response count, denominator for the analysis, or an uncertainty interval, so those quantities cannot be interpreted for this study.

ORR does not describe every aspect of disease course. It does not by itself report how long a response lasted, the timing of progression, or survival. Those are different outcomes and require their own definitions and analyses. The registry’s primary outcome description sets an assessment window of up to 18 months, but the actual assessment schedule, handling of participants without a follow-up scan, and analysis population are not reported in the registry record. The enrolled count should therefore not be assumed to be the ORR denominator.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The following statistical explanations are general. They describe how the methods relevant to this kind of outcome can be understood; they are not claims about analyses performed in this trial. The registry record does not report an analysis plan, statistical test, confidence interval method, or primary endpoint result.

How is a response outcome represented?

For a participant-level binary endpoint such as ORR, each participant is classified according to whether the prespecified response criteria were met during the assessment period. The result is ordinarily summarized by the count meeting the definition and the number assessed. A proportion can then describe the response frequency in that analyzed group. The numerator and denominator both matter: a count without an analysis denominator does not establish a response rate, while a denominator based only on enrollment may be misleading if some participants were not assessed or were excluded from the endpoint analysis.

In this record, the endpoint definition combines CR and PR under RECIST v1.0, based on MRI assessment of target lesions, with a timeframe of up to 18 months. The registry does not report the response count or denominator. It also does not specify how missing or unevaluable scans were handled. Therefore, no trial-specific response proportion can be derived from the posted information.

What does a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a stated statistical procedure. For an estimated response proportion, it can show a range of values compatible with the data and method, rather than presenting the estimate as exact. Its width depends on factors including the amount of information and the observed pattern of responses. A confidence interval does not correct for bias in who was assessed, replace a comparator, or establish that an outcome was caused by a treatment.

No confidence interval for ORR is reported in the registry record. The record also does not state which interval procedure, if any, was prespecified. It would therefore be inappropriate to infer the precision of the primary endpoint from enrollment alone or to construct an interval as though it were the sponsor’s analysis.

Why does the single-group design matter?

In a controlled study, a treatment contrast depends on comparing outcomes between groups designed to provide a relevant counterfactual. In a single-group study, the observed outcome describes what happened among participants receiving the study regimen; it does not directly estimate a difference from a concurrent control. Differences between dose cohorts can also reflect differences in who entered each cohort, when they entered, or other factors, unless the design and analysis support a controlled comparison. The registry lists allocation as NA and does not describe randomization, so cohort differences should be read descriptively.

This distinction applies to both efficacy and safety. A count of participants with an event in a treatment group can describe reported experience, but it cannot by itself determine how much of that experience was caused by treatment. A comparison with another group would need a design and analysis appropriate to the question, and no control group is listed in this record.

How should enrollment and evaluability be distinguished?

Enrollment is a study-level count. Endpoint evaluability is specific to an outcome and usually depends on whether the required information is available under the analysis rules. The registry states that 36 patients were enrolled and that the study aimed to enroll at least 25 evaluable patients. It does not state the actual number evaluable for ORR. These two statements should not be collapsed into an assumed analysis denominator.

Missing outcome data can affect interpretation if participants without assessments differ in response from those with assessments. General approaches include defining an analysis population in advance, specifying how unevaluable participants are categorized, and examining sensitivity to plausible missing-data assumptions. The registry record does not report whether any such approaches were specified or used. No assumptions about missing scans or exclusions can therefore be made.

What do planning illustrations mean?

In general, sample-size calculations are prospective planning tools based on assumptions about the effect to be detected, variability, significance level, allocation, and analysis method. A planning illustration is not an observed result and does not demonstrate that a study had a particular probability of detecting its actual effect. The registry notes that any sample-size illustrations based on the observed effect are not the trial’s own design and are planning illustrations, not observed power. No numerical planning result is included in the registry record for interpretation.

For a single-group binary outcome, a design would ordinarily need assumptions about a benchmark response frequency and the response frequency considered meaningful, along with a statistical procedure and target precision or power. Those assumptions and a sample-size justification are not reported in the registry record. They should not be reconstructed from the observed enrollment or from any outcome that is not reported.

What can be concluded from the reported analyses?

The registry lists zero analyses and does not post a primary outcome estimate, p-value, or confidence interval. This does not establish that no analyses were conducted outside the registry; it means the registry record does not report them. General statistical interpretation depends on the estimand, analysis population, missing-data handling, and uncertainty measure, in addition to the endpoint definition. Without these details and the result, the record supports description of the planned question and design, but not a numerical efficacy conclusion.

10. Multiplicity, Missing Data and Analysis Populations

The study has a primary response outcome, a listed secondary outcome concerning treatment-emergent adverse events, and stated aims involving potential biomarkers and biological activity in tumor and surrogate tissues. Considering several outcomes or exploratory measures can raise multiplicity concerns: the more questions examined, the greater the chance that some results appear notable by chance if no analysis strategy is prespecified. In general, a protocol may identify a primary hypothesis, distinguish confirmatory from exploratory analyses, and specify any adjustment or interpretation strategy. Such a strategy is not reported in the registry record.

The record identifies 2 outcome measures and zero analyses, but it does not provide outcome estimates or state how multiple endpoints, biomarkers, or dose cohorts were handled statistically. No adjustment for multiplicity should be assumed, and no unreported biomarker result can be inferred from the stated study aims.

Missing data are also relevant to ORR. The registry reports enrollment of 36 patients and says the study aimed to enroll at least 25 evaluable patients, but it does not report the number evaluable for response, the number with missing assessments, or the rules used to define the analysis population. It does not report whether missing response assessments were excluded, treated as nonresponse, or addressed by another method. The denominator and missing-data assumptions are therefore unknown.

The registry does not describe intention-to-treat, per-protocol, safety, or other analysis populations for the primary endpoint. The group-specific safety counts are presented by dose cohort, but the population rules and follow-up duration underlying those counts are not detailed. These omissions limit the ability to assess selection, missingness, and the extent to which the reported safety figures represent all enrolled participants.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dizziness (50.0%), infection (33.3%), device related infection (33.3%), respiratory tract infection (33.3%), urinary tract infection (33.3%).

The registry lists serious adverse-event counts separately for four APR-246 plus PLD dose groups. In the 4.5g/6hr group, 11 of 28 at risk are recorded as affected; in the 4.5g/3hr group, 1 of 3; in the 4.5g/4hr group, 1 of 2; and in the 3.7g/4hr group, 2 of 3. These are descriptive group counts, not a comparison against an untreated or separate control group.

The record also lists deaths by group: 9, 1, 0, and 1, respectively, in the same order. It does not report the cause, timing, or relationship of these deaths to study treatment. The counts should not be interpreted as treatment-related deaths without that information.

Dizziness is listed as the most frequent serious adverse-event term at 50.0%; infection, device related infection, respiratory tract infection, urinary tract infection, and thrombocytopenia are each listed at 33.3%. The registry does not explain the denominator or counting method for these term percentages, or whether participants could contribute more than one event term. They should be read as registry-listed figures rather than converted into participant counts or compared across groups. The record does not provide enough detail to determine how event timing, severity, or attribution was assessed.

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

This record defines a Phase II study of APR-246 combined with PLD in platinum-resistant recurrent HGSOC with mutated TP53. It identifies ORR as the primary outcome and specifies the response criteria and assessment timeframe. It also reports enrollment and group-specific safety counts. These details describe the trial’s question and some of its recorded safety information.

The registry does not report the primary response result. There is no posted count of complete or partial responses, no ORR estimate, and no confidence interval. Consequently, the record cannot show the frequency of response observed in the study or how precisely that frequency was estimated. The completed status and enrolled count do not fill this gap.

The design also sets limits on what any observed response could establish. With no separate comparator group, an outcome among participants receiving the combination would be a description of their experience, not a direct estimate of how it compares with another treatment. The dose cohorts are not a randomized control comparison. The registry does not provide an analysis plan or details sufficient to determine how differences among those cohorts should be interpreted.

The serious adverse-event and death counts are descriptive and do not establish causation. The record does not give event attribution, timing, or a comparison group. Nor does it report the actual number of participants evaluable for response, the handling of missing assessments, or the analysis population.

Accordingly, the registry supports a careful account of the study design, endpoint definition, and selected safety counts. It does not support a conclusion about the magnitude or precision of the primary efficacy outcome, a causal treatment effect, or a comparison with other regimens. Those questions require outcome and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of why a clearly defined endpoint and a reported result are both needed. The registry specifies ORR, the RECIST v1.0 response categories, MRI assessment, and a timeframe of up to 18 months. Those details establish what the primary outcome was intended to measure. Without the response numerator, denominator, and uncertainty, however, the endpoint definition alone cannot tell readers what was observed.

The single-group design also makes the inferential boundary important. A response frequency in a treated group can describe the study participants, but it does not isolate the effect of treatment from other influences. In particular, the listed dose cohorts are not a like-for-like control comparison. Readers need to distinguish a preliminary within-group description from a comparative estimate.

The record further illustrates why enrollment and endpoint evaluability are different quantities. It records 36 patients enrolled and an aim to enroll at least 25 evaluable patients, yet does not report how many were included in the ORR analysis. Without the analysis denominator and missing-data rules, even a response count would need context to be interpreted correctly.

Finally, the safety listing communicates counts and selected event terms, but not the causal or temporal detail needed to attribute those events. Descriptive safety data are useful for understanding what the registry records, while remaining distinct from a comparative safety estimate. Overall, the trial’s statistical value to readers depends not only on its clinical question and endpoint definition, but also on transparent reporting of outcome estimates, uncertainty, analysis populations, and limitations.

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 does not report the ORR result. It gives no response counts, analysis denominator, estimate, or interval. The enrolled count cannot be substituted for the number assessed or included in the endpoint analysis, and the actual number evaluable is not reported in the registry record.

The study has no separate comparator group. The allocation field is NA, masking is none, and the design is listed as single-group. The several dose cohorts do not constitute a randomized control comparison. Any differences among them would be descriptive unless additional design and analysis information supported stronger interpretation; that information is not reported in the registry record.

The registry’s account of the sub-study enrollment is incomplete: its primary outcome population description ends before identifying the final sub-study cohort. The adverse-event listing names a 3.7g/4hr group, but the registry does not complete the corresponding description in the primary outcome population text. This limits clarity about cohort membership and endpoint analysis populations.

The statistical plan is not reported. Details missing from the record include the response analysis method, uncertainty estimation, multiplicity strategy, missing-data handling, and definitions of the primary analysis population. The registry also does not state whether cohort-specific or pooled response summaries were planned.

Safety interpretation is limited by the absence of reported event attribution, timing, and detailed counting rules. The denominator for the listed serious-event term percentages is not explained. The registry does not report how deaths were classified or whether they were considered related to treatment. These gaps mean the safety counts should remain descriptive and should not be treated as causal estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: p53 Activation in Platinum-Resistant High Grade Serous Ovarian Cancer, a Study of PLD With APR-246 — NCT03268382.
• Registry record last updated 2025-03-17; status last verified 2025-03.
• Results first posted 2022-07-21.
• 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

The registry describes NCT03268382 as a completed Phase II, single-group study of APR-246 with PLD in platinum-resistant recurrent HGSOC with mutated TP53. It records 36 patients enrolled, a start date of 2017-07-31, and a primary completion date of 2019-07-10. Allocation is NA and masking is none.

The primary outcome is ORR by RECIST v1.0 assessment of target lesions using MRI, over up to 18 months. The record defines response as CR plus PR but does not report the response result, analysis denominator, or uncertainty. Treatment-emergent adverse events are listed as a secondary outcome, with serious-event counts and selected event terms reported by dose group.

The registry does not report the statistical analysis plan, analysis populations, or missing-data procedures. The absence of a comparator and primary efficacy results limits interpretation to the recorded design and descriptive safety information.