PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (NCT04556617), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Dose-Limiting Toxicities.

2. Clinical Question

The study’s stated purpose was to evaluate safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PLX2853 in subjects with mCRPC. Those aims describe what the research sought to evaluate; they do not establish that results for each aim were reported. The registry record does not report pharmacokinetic, pharmacodynamic, or preliminary efficacy results. It also does not report a treatment-effect estimate comparing the combinations.

The clinical question is therefore chiefly an early-phase safety question in the posted record: what dose-limiting toxicities were observed during the specified first-cycle period in the groups receiving these combinations? That question is distinct from whether one regimen is more effective than another. With non-randomized allocation and no like-for-like control comparison, differences between groups could not be interpreted as unbiased comparative treatment effects on the basis of this design alone.

3. Trial Design

This was a multicenter, open-label, parallel study in Phase 1b and Phase 2a. Allocation was non-randomized and masking was none. The registry lists enrollment of 19 and status as terminated. The recorded start date is 2020-09-21, and the primary completion date is 2022-05-24. The reason for termination is not reported in the registry record.

The five listed groups combined PLX2853 with either olaparib or abiraterone acetate and prednisone. Phase 1b dose-escalation groups were PLX2853 20 mg plus olaparib; PLX2853 40 mg plus olaparib; PLX2853 40 mg plus abiraterone acetate and prednisone; and PLX2853 80 mg plus abiraterone acetate and prednisone. The phase 2a group was PLX2853 80 mg plus abiraterone acetate and prednisone and was described as a dose expansion. The record does not report how participants were assigned among these groups or the number enrolled in each group as an enrollment plan.

Because the study was open-label, treatment masking was not used. Because allocation was non-randomized, group membership may reflect factors other than chance; the registry record does not state the assignment process. The phase and dose-escalation descriptions indicate an early-stage investigation, but the record does not report the protocol’s dose-escalation rules, stopping boundaries, or rationale for the chosen doses. Those details should not be inferred from the group labels.

The record lists three outcome measures, but the primary outcome is the only one described in the available trial details. The registry record lists zero analyses. Statistical methods for comparing groups, handling repeated observations, or adjusting for participant characteristics are not reported in the registry record. Consequently, the design supports a description of the reported groups and outcomes, not a randomized comparison of the combinations.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose-Limiting Toxicities, measured over From time of first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days).

The primary endpoint is the number of participants with dose-limiting toxicities. The registry defines a dose-limiting toxicity as a clinically significant adverse event or laboratory abnormality arising during the first cycle of study drug administration, possibly related to study drug, and meeting specific criteria defined in the protocol. The assessment period runs from the first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days).

In early-phase dose escalation, this kind of endpoint is used to characterize tolerability during a defined treatment window. A count of affected participants is a binary-outcome summary at the participant level: each participant either meets the stated endpoint definition or does not. That general framing does not specify how the protocol’s criteria were applied to individual cases, and the criteria themselves are not reproduced in detail in the registry record.

The endpoint is not a complete measure of all safety experiences over the entire study, because its stated observation window is limited to the first cycle. It also is not an efficacy endpoint. The registry record does not report the observed number of participants with dose-limiting toxicities, an estimate of the proportion meeting the definition, or uncertainty around such an estimate. The listed serious and other adverse-event summaries are separate safety information and should not be treated as a substitute for the primary endpoint result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is a count of participants who met the protocol definition of dose-limiting toxicity during a specified period. General statistical explanation: for a binary outcome, each participant’s status is classified into one of two categories, such as meeting or not meeting the endpoint definition. A count can describe how many participants had the event, but a count alone does not show the uncertainty of an estimated event frequency. To interpret a frequency, the relevant denominator and the rules for determining who was assessed are also important.

In this record, the endpoint definition includes clinical significance, possible relation to study drug, timing during the first cycle, and protocol-defined criteria. Those criteria determine which events qualify. The registry record does not report the primary endpoint count, the participant-level assessments, or details on adjudication. It is therefore not possible to reconstruct endpoint results from the posted safety summaries.

Why does the assessment window matter?

The primary endpoint is assessed from the first dose of PLX2853 and combination agent(s) through completion of Cycle 1 (21 days). A window defines which observations contribute to the endpoint. Events outside that period may be relevant to overall safety but would not be included in this particular endpoint as described. General statistical explanation: consistent observation windows make outcome definitions clearer, while differing follow-up can complicate comparisons if participants are not observed for the same period. The registry record does not report participant-level follow-up or whether any participants did not complete the endpoint window.

How should non-randomized groups be interpreted?

Random allocation is one way to balance measured and unmeasured participant characteristics across treatment groups on average. This study was non-randomized, and the registry does not report the assignment process. Consequently, treatment-group differences could reflect differences in participant characteristics, treatment combinations, dose levels, or other factors, not solely a treatment effect. This is a general limitation of non-randomized comparisons, not a finding about why participants entered a particular group in this study.

The groups also represent different combinations and doses, rather than parallel versions of one regimen with a single controlled change. The registry record does not report a prespecified pairwise comparison or statistical adjustment that would make the groups directly comparable. The posted summaries should therefore be read as descriptions of the individual groups rather than estimates of relative treatment effects.

What does a confidence interval add?

General statistical explanation: a confidence interval expresses uncertainty around an estimate under a specified statistical model and procedure. It is not a guarantee that the true value lies within the interval, and it does not remedy limitations in design or data collection. For a participant-level event outcome, an interval around an event frequency would help convey how much precision the observed data support. The registry record does not report a primary endpoint estimate or confidence interval, so precision for the primary outcome cannot be assessed from the record.

Over-dispersion is a general issue for count data when variability exceeds what a basic count model expects. It can make model-based standard errors too small if the extra variability is ignored. That concept does not establish that over-dispersion occurred in this study: the primary outcome is described as a participant count, and the registry record does not report a statistical model, a dispersion estimate, or an analysis of count outcomes.

What do the planning assumptions mean?

The registry describes a sample-size planning illustration computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was designed with those parameters, and the registry does not state that they were the trial’s own design assumptions. The illustration is not observed power. Sample-size planning asks how much information a future study might require under specified assumptions; it does not change the precision or strength of evidence in the current study.

For a binary endpoint, a normal approximation is a general approach that uses an approximate distribution for an estimated difference or other contrast. Such approximations may be less reliable when data are sparse; alternative methods may be considered in statistical practice. The registry record does not report the illustration’s exact outputs, a power calculation used to plan this trial, or a statistical analysis plan for the clinical outcomes. No additional planning values or trial-design rationale can be inferred.

What is the scope of the posted statistical evidence?

The registry lists three outcome measures and zero analyses. This means the record does not present a set of inferential analyses for the listed study outcomes. It does not establish whether analyses were conducted outside the registry record. No model, effect measure, confidence interval, hypothesis test, covariate adjustment, or multiplicity procedure is reported in the registry record. General statistical concepts can explain what such methods would do, but they cannot supply missing trial results or justify a comparison that the design does not support.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Phase 1b PLX2853 (20 mg) + Olaparib", "Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + P", "Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + P", "Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + P", "Phase 1b PLX2853 (40 mg) + Olaparib")
n      <- c(1, 5, 7, 5, 1)
events <- c(0, 0, 0, 0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Phase 1b PLX2853 (20 mg) + Olaparib  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  Phase 1b PLX2853 (40 mg) + Abiraterone Acetate + P  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Phase 1b PLX2853 (80 mg) + Abiraterone Acetate + P  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  Phase 2a PLX2853 (80 mg) + Abiraterone Acetate + P  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Phase 1b PLX2853 (40 mg) + Olaparib  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates more than one outcome, comparison, dose, or analysis and makes multiple statistical claims. Without a prespecified approach, repeated testing can increase the chance of at least one false-positive result. The registry lists three outcome measures, but the record does not report a multiplicity strategy, a hierarchy of outcomes, or adjusted significance thresholds. It also lists zero analyses, so no multiplicity-adjusted results are available in the registry record.

The study includes several dose groups and two combination approaches. That structure creates possible descriptive and comparative questions, but the registry record does not identify which comparisons, if any, were prespecified for statistical testing. No inferential comparison should be assumed from the existence of multiple groups. The primary endpoint is named, but the record does not report its result or an analysis plan for it.

Missing-data methods and analysis populations are not reported in the registry record. The record does not state how participants who discontinued, missed an assessment, or lacked endpoint data were handled. It also does not describe an intention-to-treat, safety, per-protocol, or other analysis population for the endpoint. The enrollment figure does not establish how many participants contributed to each outcome analysis.

These omissions matter because outcome availability and analysis-population definitions affect the interpretation of event counts and comparisons. They do not prove that data were missing or that any particular analysis population was used. The registry record simply does not report those details, so readers cannot evaluate their effect on the posted results.

12. 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: pleural effusion (100.0%), bone pain (20.0%), blood bilirubin increase (20.0%), pulmonary embolism (20.0%), hyperglycemia (14.3%).

The safety record reports participant counts by group for serious adverse events, other adverse events, and deaths. For serious adverse events, the listed at-risk and affected counts are: PLX2853 20 mg plus olaparib, 1 and 1; PLX2853 40 mg plus abiraterone acetate and prednisone, 5 and 1; PLX2853 80 mg plus abiraterone acetate and prednisone in phase 1b, 7 and 3; PLX2853 80 mg plus abiraterone acetate and prednisone in phase 2a, 5 and 2; and PLX2853 40 mg plus olaparib, 1 and 0. The reported death count is 0 in each group.

For other adverse events, the at-risk and affected counts are 1 and 1, 5 and 5, 7 and 7, 5 and 5, and 1 and 1 in those same respective groups. These figures are descriptive and do not establish causality. The treatment groups are non-randomized and differ in regimen and dose, so their counts are not a like-for-like comparative safety analysis.

The registry lists pleural effusion at 100.0%, bone pain, blood bilirubin increase, and pulmonary embolism at 20.0% each, and hyperglycemia and urinary tract obstruction at 14.3% each among the top serious-event terms. The denominator for these term percentages is not reported in the registry record. Term listings and group-level counts should not be substituted for the primary dose-limiting-toxicity endpoint.

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

The record supports a description of an early-phase, non-randomized investigation of PLX2853 combinations in subjects with metastatic castration-resistant prostate cancer. It identifies the treatment groups, the primary dose-limiting-toxicity endpoint, and descriptive adverse-event counts. These details help define what the study set out to examine and what safety information the registry posts.

The record does not report the primary endpoint result. It therefore cannot establish how many participants met the dose-limiting-toxicity definition or how precisely that endpoint was estimated. The posted serious and other adverse-event counts provide separate descriptive information, but they do not answer the primary endpoint question by themselves. Nor do the registry entries report pharmacokinetic, pharmacodynamic, or preliminary efficacy results.

The non-randomized allocation is central to interpretation. The groups differ in combinations and dose levels, and no like-for-like randomized control comparison is reported. Any numerical differences in descriptive safety counts across groups should not be interpreted as evidence that one regimen caused more or fewer events than another. The record reports no comparative statistical analyses to support such a conclusion.

The study’s terminated status is a registry status, not an explanation of why it ended. The reason for termination is not reported in the registry record. It should not be used to infer a safety problem, lack of efficacy, or an operational decision. Likewise, a stated research purpose does not show that the corresponding outcomes were achieved or that any treatment has a particular clinical effect.

In short, the posted information documents the study structure and selected safety summaries, but leaves the primary outcome and other stated research aims without reported results. It can inform understanding of the design and the limits of the available evidence; it cannot establish comparative benefit or harm.

14. Why This Trial Matters Statistically

This study illustrates why design details are essential when interpreting early-phase trial results. Dose escalation and dose expansion address different stages of investigation, and the record identifies both within a single multicenter, parallel study. The primary endpoint is a protocol-defined count within a specific first-cycle window, not a broad measure of all safety or efficacy outcomes.

The non-randomized allocation also demonstrates an important boundary between description and comparison. Treatment-group counts can convey what was recorded in each group, but differences between those counts do not isolate the effect of dose or combination. Group membership was not randomized, and the registry record does not report a comparative analysis that accounts for possible differences between participants.

Another statistical lesson is that an endpoint’s name and definition do not substitute for its result. Although the primary measure is clearly identified, its outcome count is not reported in the registry record. Without the result and a measure of uncertainty, the endpoint cannot be interpreted quantitatively. The same distinction applies to the stated goals of evaluating pharmacokinetics, pharmacodynamics, and preliminary efficacy: aims are not findings.

The record also highlights the importance of transparency about analysis populations, missing data, and multiplicity. Those methods shape how outcome summaries should be read, yet they are not reported. Their absence from the registry record limits independent evaluation; it does not prove that no such procedures were used elsewhere.

Finally, planning assumptions should be kept separate from observed evidence. A sample-size illustration based on an effect and specified statistical assumptions is a planning exercise, not observed power and not evidence that a trial has demonstrated an effect. Clear separation of design, descriptive safety, analysis methods, and outcome results is especially important when a study has several groups but no randomized control comparison.

15. 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 most important limitation of the available record is that it does not report the primary dose-limiting-toxicity result. Although the endpoint definition and observation window are specified, the corresponding participant count and its uncertainty are not. The registry also does not report results for pharmacokinetics, pharmacodynamics, or preliminary efficacy, despite identifying those areas in the study purpose.

The study was non-randomized and had no masking. The record does not explain how group assignment occurred or report a randomized comparator. Its groups used different combinations and doses, so the posted safety counts cannot support a like-for-like treatment comparison. Participant characteristics and eligibility details beyond the disease condition are not reported in the registry record, limiting assessment of how comparable the groups may have been.

Analysis methods are also sparsely documented. The registry lists zero analyses and does not report a statistical analysis plan, inferential methods, uncertainty estimates, multiplicity procedures, missing-data handling, or analysis-population definitions. It does not report why the study was terminated. These omissions restrict interpretation of both the design and the descriptive results.

The serious-event term percentages are listed, but their denominator is not reported in the registry record. They should not be treated as directly comparable risks across groups. The primary endpoint’s protocol-specific criteria are referenced but not fully detailed in the record, so independent application of the definition is not possible from the posted description alone.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PLX2853 in Combination With Abiraterone Acetate and Prednisone and in Combination With Olaparib in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) — NCT04556617.
• Registry record last updated 2025-04-08; status last verified 2025-04.
• 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.

19. Record Summary

NCT04556617 is a multicenter, open-label, parallel Phase 1b/2a study of PLX2853 combined with olaparib or with abiraterone acetate and prednisone in subjects with metastatic castration-resistant prostate cancer. Allocation was non-randomized, masking was none, enrollment was 19, and the registry status is terminated.

The primary endpoint was the number of participants with dose-limiting toxicities from the first dose through completion of Cycle 1 (21 days). The registry record does not report that endpoint’s result, the reason for termination, or results for the stated pharmacokinetic, pharmacodynamic, and preliminary efficacy aims. It lists serious and other adverse-event counts by group, with a death count of 0 in each group. The record lists three outcome measures and zero analyses.