PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers (NCT04209595), a non-randomized phase 1, phase 2 study. The primary outcome is Phase II: Clinical Benefit Rate.

2. Clinical Question

3. Trial Design

This was a Phase I/II, non-randomized, unmasked, sequential trial sponsored by the National Cancer Institute. The registry lists total enrollment of 10 and a completed status. The study started on 2020-04-08, and primary completion was recorded as 2021-08-13. These dates describe the trial record and do not indicate that the planned Phase II efficacy assessment was completed.

The Phase I portion enrolled participants with solid tumors to dose-escalation groups involving PLX038 and rucaparib. The record lists a PLX038 dose of 1.3 g/m^2 every 3 weeks in the described groups. It lists rucaparib total doses of 200 mg, 300 mg, or 400 mg, with different treatment days in the dose-group descriptions. The registry describes the Phase II groups as participants with small cell lung cancer and extra-pulmonary small cell carcinomas, enrolled at the maximum tolerated dose after it was established.

The record describes PLX038 as an intravenous treatment and rucaparib as an oral treatment taken twice daily. The brief summary describes PLX038 on Day 1 of a 21-day cycle and rucaparib on specified days within each cycle, while the individual arm descriptions give different rucaparib days for dose groups. These schedules should be understood in the context of the particular dose-group descriptions, rather than treated as one uniform regimen across the entire study.

Because allocation was non-randomized and masking was absent, the design was intended to assess combination dosing and planned clinical outcomes, not to provide a randomized comparison against another treatment. The registry lists no analyses for the outcomes. Further details of the protocol, including the dose-escalation decision rules and the statistical analysis plan, 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: The phase II portion of the study was not done because the study was closed to enrollment due to Clovis Oncology withdrawing support for the study.

Phase I - Maximum Tolerated Dose

Phase IIA - Assess Efficacy

Phase IIB - Assess Efficacy

Analysis population for the primary outcome, as defined in the registry: This outcome measure was not done because the study was closed to enrollment due to Clovis Oncology withdrawing support for the study. No data was collected for this phase II outcome measure.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Phase II: Clinical Benefit Rate, measured over Disease progression at 4 months.

The primary listed Phase II endpoint was clinical benefit rate, expressed as a proportion of participants. It combined three RECIST 1.1 outcome categories: complete response, partial response, and stable disease lasting 4 months. A complete response means target lesions have disappeared, with any pathological lymph nodes reduced below the stated short-axis criterion. A partial response requires a decrease in the sum of target-lesion diameters relative to baseline. Stable disease means the changes meet neither the threshold for partial response nor the threshold for progressive disease, using the specified reference measurements.

This composite endpoint was intended to capture more than tumor shrinkage alone. It counts a complete or partial response, but also stable disease that persists for the stated duration. The duration condition distinguishes short-term disease stability from stability maintained through the endpoint's assessment period. The registry identifies RECIST as the method for assessing response and gives disease progression at 4 months as the timeframe.

However, these definitions describe the planned measure, not an observed trial result. The registry states that the study closed to enrollment because Clovis Oncology withdrew support, and no data were collected for this Phase II outcome. Therefore, the posted record does not provide a clinical benefit estimate or its 95% confidence interval for the planned Phase II population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the clinical benefit rate represent?

In general, a proportion summarizes how many participants in a defined group meet a specified outcome. A clinical benefit rate is a composite proportion: a participant is counted if they meet at least one of the included response categories. For this trial, those categories were complete response, partial response, or stable disease lasting 4 months according to RECIST 1.1. The measure is not the same as a tumor-shrinkage rate alone because stable disease can also qualify, provided it lasts for the specified period.

Composite outcomes can be useful when the scientific question concerns several clinically relevant forms of disease control. Their interpretation depends on the exact components and the assessment window. Here, the registry describes the components and the 4-month duration, but the planned outcome was not collected. Thus, the endpoint definition can be explained, but there is no observed proportion to interpret.

What does a confidence interval communicate?

In general, a confidence interval conveys the statistical uncertainty around an estimated quantity, such as a proportion. A narrower interval indicates greater precision under the method used; a wider interval indicates less precision. It does not remove limitations in the study design, correct for missing outcome data, or show that a treatment caused an outcome. The registry lists a 95% confidence interval as the planned dispersion measure for the Phase II clinical benefit rate, but no Phase II outcome data were collected. Therefore, no interval for that endpoint is reported in the registry record.

Why does the design matter for interpretation?

Random allocation is one way to balance participant characteristics across comparison groups, on average. This trial was non-randomized and sequential. Its Phase I dose groups and planned Phase II disease groups were not set up as randomized, like-for-like treatment comparisons. The Phase I groups differ in listed rucaparib dose and schedule. Consequently, comparing their adverse-event counts cannot isolate the effect of dose from other differences between participants or groups.

Sequential dose escalation is generally used to evaluate dose levels in sequence rather than to estimate a treatment effect against a concurrent randomized control. The registry identifies a sequential model and describes Phase II enrollment after the maximum tolerated dose was established. The specific escalation rules, decision boundaries, and detailed statistical procedures are not reported in the registry record. No assumptions about those procedures can be made from the design labels alone.

How should the safety counts be read?

The registry gives participants at risk and participants affected for serious and other adverse events in the listed Phase I groups. In general, an at-risk denominator identifies the group in which events were assessed, while the affected count identifies participants recorded with an event category. These counts do not by themselves describe how many events each participant experienced, their timing, or their severity distribution. The registry also gives selected serious-event terms as percentages, but the corresponding detailed event-level information is not reported in the registry record.

Adverse-event categories may overlap in general: one participant may experience more than one type of event. Therefore, term percentages should not be added together to infer a total, and a participant affected by one event category may also appear in another. The record's counts and term listings should be read as separate safety summaries unless a specific aggregation method is stated. A detailed method for how these terms were coded or summarized is not reported in the registry record.

What do planning calculations mean?

In general, sample-size calculations are planning tools that estimate the number of participants needed under stated assumptions to target a chosen level of statistical power for detecting an effect. The record's planning assumptions describe two-sided significance level 0.05, equal allocation, a normal approximation, and an effect expressed as a fraction of the observed effect. Those calculations are illustrations, not the trial's own design, and they do not constitute observed power. For time-to-event calculations, the stated convention concerns total events; for other calculations, the convention is participants per arm.

These assumptions do not imply that the trial used equal allocation or had a randomized two-arm comparison. The registered study was non-randomized, sequential, and had a total enrollment of 10. The Phase II primary endpoint was not collected, so there is no Phase II observed clinical benefit effect in this record from which to make an efficacy interpretation. The protocol's sample-size justification is not reported in the registry record.

What statistical details remain unknown?

The registry lists 8 outcome measures and 0 analyses. It identifies no outcome analysis results for the primary Phase II endpoint. A complete statistical plan, including analysis populations, handling of missing data, multiplicity procedures, covariate adjustment, and any interim-analysis plan, is not reported in the registry record. The absence of a listed analysis does not show that a method was or was not used outside the record; it means that the record does not document it. Statistical interpretation should therefore remain bounded by the posted endpoint definitions, study design, and safety summaries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures, including the Phase II clinical benefit rate, progression-free survival, overall survival, and a Phase I clinical response measure. It does not report a multiplicity strategy for interpreting several outcomes or multiple comparisons. In general, when many endpoints or comparisons are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiplicity. No adjustment method, hierarchy, or designation of confirmatory versus exploratory analyses is reported in the registry record.

The primary Phase II outcome has a clear missingness issue at the study level: the registry says the measure was not done because enrollment closed after Clovis Oncology withdrew support, and no data were collected for that outcome. This is not an observed clinical benefit rate of zero. It is an unobserved endpoint, so an estimate and confidence interval cannot be calculated from the Phase II data described in the record.

Participant-level missing-data handling for other outcomes is not reported in the registry record. Nor are the analysis populations, rules for excluding participants, or methods for handling incomplete follow-up reported. The record lists 0 analyses, so it does not document inferential results, adjusted estimates, or sensitivity analyses. Any analysis populations or missing-data procedures beyond the stated absence of Phase II outcome data are not reported in the registry record.

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: gastrointestinal disorders - other, neutropenic enterocolitis (100.0%), febrile neutropenia (50.0%), neutrophil count decreased (50.0%), sepsis (50.0%), anemia (12.5%).

The serious adverse-event summaries concern the Phase I dose groups, not a randomized comparison. In the 400 mg rucaparib group, 8 participants were at risk and 3 were reported as affected by serious adverse events. In the 300 mg group, 2 participants were at risk and 2 were affected. For other adverse events, the corresponding counts are 8 at risk and 8 affected in the 400 mg group, and 2 at risk and 2 affected in the 300 mg group.

The registry lists serious-event terms and percentages: gastrointestinal disorders - Other, Neutropenic Enterocolitis, 100.0%; febrile neutropenia, 50.0%; neutrophil count decreased, 50.0%; sepsis, 50.0%; anemia, 12.5%; and diarrhea, 12.5%. The record does not specify in the registry record the denominator or detailed event-level counting method for each term, so the percentages should be read as registry-reported summaries, not used to reconstruct participant counts.

Deaths are listed as 7 in the 400 mg group and 2 in the 300 mg group. Causes, timing, and attribution are not reported in the registry record. These figures alone do not show that deaths were caused by study treatment.

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

The record documents a trial that investigated the combination of PLX038 and rucaparib through Phase I dose escalation and planned Phase II disease cohorts. It gives safety counts for the listed Phase I groups and specifies the clinical benefit outcome intended for Phase II. These are distinct types of information: the Phase I counts describe recorded safety summaries, while the Phase II endpoint describes an efficacy question that was not answered in the posted record.

The planned endpoint would have counted participants with complete response, partial response, or stable disease lasting 4 months under RECIST 1.1. Because no data were collected for this Phase II outcome, there is no registry-based clinical benefit estimate to interpret. The absence of an estimate does not mean the endpoint was met by no one or by everyone; it means the outcome was not assessed for the planned Phase II analysis.

The safety counts should not be treated as proof of a causal relationship, nor compared as though the dose groups were randomized. The groups were small, sequential, and had different listed rucaparib regimens. The record does not provide a concurrent randomized control group or the details needed to attribute outcomes to a particular treatment component. The listed deaths also have no reported cause or treatment attribution in the registry record.

In general, trial results are interpreted in light of design, endpoint definition, follow-up, analysis methods, and precision. Here, the registry record provides the design labels and some safety summaries, but not a Phase II efficacy result or a detailed statistical analysis. It therefore supports a careful account of what was planned and what safety summaries were recorded, not a conclusion about comparative efficacy or a treatment effect.

13. Why This Trial Matters Statistically

This trial is statistically informative because it separates two questions that can otherwise be conflated. The Phase I portion concerned dose escalation and combination safety in participants with solid tumors. The Phase II portion planned to estimate a clinical benefit rate in small cell lung cancer and extra-pulmonary small cell carcinomas. The registry record contains Phase I safety summaries, but the planned Phase II efficacy outcome was not collected. Recognizing that distinction prevents a safety summary from being mistaken for an efficacy result.

The non-randomized, sequential design also matters. Dose groups at different rucaparib levels are not interchangeable with randomized arms. Their counts can describe what was recorded in each group, but they do not provide an unbiased head-to-head estimate of the effect of one dose versus another. This is particularly important when the groups are small and differ in treatment schedules.

The record also illustrates the difference between a defined endpoint and an observed endpoint. The Phase II measure is clearly specified using RECIST 1.1 and a 4-month stability criterion, and a 95% confidence interval was planned. Yet an endpoint definition and a planned statistical measure do not substitute for outcome data. With no data collected for the Phase II endpoint, neither its estimated proportion nor its precision can be assessed.

Finally, the safety record is best read with attention to denominators, event categories, and missing context. Participants could contribute to different event categories, and the listed term percentages do not on their own describe event timing, severity, or attribution. These limitations make disciplined interpretation essential: report what the record documents, and avoid extending it to claims the design or results cannot support.

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 most important limitation is that the planned Phase II primary outcome was not performed. The registry attributes closure to Clovis Oncology withdrawing support and states that no data were collected for the clinical benefit rate. Consequently, there is no Phase II efficacy estimate, confidence interval, or outcome comparison available in the record.

The design was non-randomized, unmasked, and sequential. The Phase I dose groups are not randomized controls, and their treatment schedules differ. Total enrollment was 10, with 8 participants listed in the 400 mg group and 2 in the 300 mg group for the adverse-event summaries. These small group counts limit how precisely the safety experience can be characterized, and do not support reliable comparisons between dose groups.

The registry entries do not provide detailed participant characteristics, duration of follow-up, event timing, causes or attribution of deaths, or complete event-level safety details. The statistical analysis plan, protocol sample-size justification, analysis populations, missing-data procedures, multiplicity strategy, and interim-analysis plan are not reported in the registry record. The registry lists 0 analyses. These omissions constrain evaluation of how outcomes were to be analyzed and how much uncertainty would surround any estimates.

The trial's completed status and primary completion date should not be taken to imply that the planned Phase II efficacy endpoint was observed. The record explicitly says it was not done. The available information therefore supports a limited description of the trial design and Phase I safety summaries, rather than conclusions about the Phase II clinical benefit question.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: PLX038 (PEGylated SN38) and Rucaparib in Solid Tumors and Small Cell Cancers — NCT04209595.
• Registry record last updated 2026-08-26; status last verified 2026-08.
• Results first posted 2024-01-03.
• 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

NCT04209595 is a completed, non-randomized, unmasked Phase I/II trial sponsored by the National Cancer Institute. It evaluated PLX038 with rucaparib in solid tumors and small cell cancers. The registry lists enrollment of 10, a start date of 2020-04-08, and primary completion on 2021-08-13.

Phase I involved sequential dose groups. The posted safety summaries list serious and other adverse events for groups receiving rucaparib total doses of 400 mg and 300 mg alongside PLX038. The record also lists serious adverse-event terms and deaths, without reporting death causes or attribution in the registry record.

The planned Phase II primary endpoint was clinical benefit rate, defined as complete response, partial response, or stable disease lasting 4 months by RECIST 1.1. The registry states that the endpoint was not assessed because enrollment closed after Clovis Oncology withdrew support, and no Phase II outcome data were collected. A detailed statistical analysis plan and the protocol's sample-size justification are not reported in the registry record.