Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer (NCT04514497), a non-randomized phase 1 study. The primary outcome is Maximum Tolerated Dose (MTD) (Dose Escalation Phase) of Elimursertib.

2. Clinical Question

The trial asks whether BAY 1895344, also called elimusertib in the registry record, can be given with irinotecan or topotecan in people with advanced solid tumors, and what dose is tolerated during dose escalation. It has a specific focus on small cell lung cancer, poorly differentiated neuroendocrine carcinoma, and pancreatic adenocarcinoma. The primary endpoint concerns the maximum tolerated dose, not whether the combinations improve tumor outcomes. Objective response, duration of response, progression-free survival, overall survival, and drug exposure are listed as secondary outcomes.

The central statistical question is therefore about tolerability and dose selection in the study’s dose-escalation phase. The posted record does not give a numerical maximum tolerated dose, a count of dose-limiting toxicities by dose level, or a treatment-effect estimate for the secondary tumor outcomes. Those outcomes are listed, but their results are not reported in the registry record.

3. Trial Design

This is a Phase I, nonrandomized, unmasked, parallel study sponsored by the National Cancer Institute (NCI). The registry records enrollment of 29 participants. Its title describes dose-escalation studies with expansion cohorts in small cell lung carcinoma, poorly differentiated neuroendocrine carcinoma, and pancreatic adenocarcinoma. The study status is active, not recruiting. The recorded start date is 2021-10-20, and the primary completion date is 2025-02-15.

The registry describes three treatment cohorts. Cohort I combines elimusertib taken by mouth twice daily on days 1 and 2 with irinotecan given intravenously on day 1; cycles repeat every 14 days if there is no disease progression or unacceptable toxicity. Cohort II combines elimusertib taken by mouth once daily on specified days with irinotecan given intravenously on specified days; cycles repeat every 21 days. Cohort III combines elimusertib taken by mouth once daily on days 2 and 5 with topotecan given intravenously on days 1–5; cycles repeat every 21 days if there is no disease progression or unacceptable toxicity. These are different regimens, not randomized treatment alternatives.

Participants undergo imaging with computed tomography and/or magnetic resonance imaging, and the registry lists tumor biopsies and biospecimen collection. The listed secondary outcomes include objective response rate, duration of response, progression-free survival, overall survival, and pharmacokinetic measures for elimusertib and irinotecan. The record lists 18 outcome measures overall. It does not report the allocation procedure between cohorts, a detailed recruitment target for each cohort, or the statistical analysis plan.

Because assignment is nonrandomized and cohort regimens differ, comparisons across cohorts cannot be interpreted as controlled estimates of relative treatment effects. The study design is primarily suited to describing dose escalation, tolerability, and outcomes within the studied regimens. Any broader comparison would require an analysis plan and design information 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.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Maximum Tolerated Dose (MTD) (Dose Escalation Phase) of Elimursertib, measured over Up to 21 days (first treatment cycle).

The primary endpoint is the maximum tolerated dose (MTD) in the dose-escalation phase, recorded in milligrams. The registry defines this endpoint through dose-limiting toxicities (DLTs) during cycle 1, with a timeframe of up to 21 days. Its description says the MTD is defined by the occurrence of at least 2 DLTs at any dose level during cycle 1. Listed DLTs include grade 4 neutropenia lasting at least 7 days, grade 4 thrombocytopenia, grade 4 anemia, and grade 3 neutropenia with fever. Other qualifying events include grade 3 thrombocytopenia with bleeding, specified grade 3 hematologic toxicities lasting at least 7 days, and non-hematologic adverse events of grade 2 or higher lasting at least 7 days, with stated exceptions for grade 2 fatigue, nausea, or diarrhea. Toxicities are to be graded using Common Terminology Criteria for Adverse Events version 5.0.

General: In early-phase dose escalation, an MTD endpoint is used to characterize the dose associated with unacceptable toxicity under the study’s operational definition. This is a dose-selection measure, not a direct measure of antitumor benefit. The registry record does not report the observed MTD, the dose-level DLT counts, or the result of the dose-escalation decision. The endpoint’s definition is available, but its numerical result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a dose-escalation endpoint and lists multiple secondary outcomes, but it does not describe the statistical methods used to analyze them. The following distinctions help interpret what is and is not available in the posted material.

What does a dose-limiting toxicity rule do?

General: A dose-limiting toxicity rule translates observed adverse events into a decision criterion for dose escalation. It defines which events count, how severe or persistent they must be, and the observation period in which they are evaluated. Those details matter because changing an event definition or assessment window can change which participants count as having a DLT. Here, the registry specifies the event categories, duration criteria, exceptions, and first-cycle timeframe. It also states that toxicities are graded under Common Terminology Criteria for Adverse Events version 5.0.

The record says the MTD is defined by the occurrence of at least 2 DLTs at any dose level during cycle 1. It does not report the number of participants evaluated at each dose level, the observed DLT counts at those levels, or how incomplete observation was handled. It also does not report a dose-escalation algorithm or any additional decision rules. The posted endpoint definition should therefore not be expanded into an assumed protocol for escalation.

What can be learned from a count endpoint?

The primary outcome is a dose, with milligrams as its unit, rather than a comparison of average outcomes between treatment groups. The registry records the endpoint parameter as a number, but does not post a numerical value. A count or dose summary can describe the result of a dose-finding procedure only when the underlying observations and decision are available. Without them, readers cannot reconstruct which dose levels were assessed or how the stated MTD criterion was met.

How should secondary outcomes be understood?

Objective response rate summarizes whether tumors meet the study’s response criteria. Duration of response measures how long a response lasts, while progression-free survival and overall survival are time-to-event outcomes. General: Time-to-event analyses account for both the timing of an event and the fact that some participants may not have experienced it by the end of observation. Their interpretation depends on the event definition, follow-up, censoring rules, and analysis method. These details are not reported in the registry record.

The listed pharmacokinetic outcomes are maximum concentration and area under the concentration-time curve for elimusertib, and maximum concentration and area under the concentration-time curve for irinotecan. General: Maximum concentration describes a peak measured drug concentration, while area under the concentration-time curve summarizes exposure over a defined sampling interval. The record lists these outcomes but does not report their estimates, sampling details, or analysis methods.

What do the planning illustrations represent?

The sample-size section is a planning illustration based on an observed effect, not the trial’s own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the illustration concerns the total number of events; for other tables, it concerns participants per arm for 80% power or another stated power level. Such calculations are hypothetical planning quantities. They are not observed power, do not describe the enrollment plan for this nonrandomized study, and do not turn its cohorts into a controlled comparison. No illustration values are repeated.

General: A confidence interval expresses uncertainty around an estimated quantity, while a hypothesis test evaluates compatibility with a specified null model under its assumptions. Neither can be interpreted without the estimate, analysis population, model, and assumptions. No confidence intervals, test statistics, or p-values for trial outcomes are reported in the registry record. The record also does not report how multiplicity, missing outcome data, or analysis populations were handled.

Why does the nonrandomized design matter?

In a randomized comparison, assignment can support a more direct comparison between groups, subject to the trial’s conduct and analysis. Here, the registry identifies nonrandomized allocation and states that the arms are not a like-for-like control comparison. The cohorts also use different combinations and schedules. General: Differences between groups in a nonrandomized study can reflect participant characteristics, treatment selection, dose, schedule, or other factors, as well as chance. Without a prespecified comparative analysis and adequate adjustment, between-cohort contrasts should remain descriptive.

In short, the registry gives the endpoint definition, cohort regimens, and selected adverse event counts, but not the analysis methods or outcome estimates needed for formal statistical interpretation. The record does not report a protocol-level statistical plan, interim analyses, model specifications, or a sample-size justification.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures, including the primary MTD endpoint and secondary tumor, survival, and pharmacokinetic outcomes. It records 0 analyses. The posted record therefore does not provide a family of analysis results from which to assess how many statistical tests were performed or how the chance of false-positive findings was managed.

Multiplicity arises when several outcomes, groups, time points, or hypotheses are examined. General: If many tests are conducted, interpreting an isolated statistically significant result without a prespecified strategy can overstate the strength of evidence. Possible strategies include designating a primary outcome, controlling an error rate, or treating other results as exploratory. The registry identifies a primary endpoint, but any multiplicity procedure beyond that designation is not reported in the registry record.

The record does not describe missing-data rules, censoring conventions for survival outcomes, or which participants were included in each analysis population. It does not state whether analyses were based on all enrolled participants, participants who received treatment, or participants with evaluable outcomes. These distinctions matter because exclusions or incomplete follow-up can affect both denominators and estimates.

No interim analyses, stopping rules beyond the endpoint’s DLT definition, or statistical analysis plan are reported in the registry record. These omissions limit assessment of selective reporting and the handling of incomplete observations. They do not establish that such methods were absent from the full study documentation; they mean only that they are not available in this 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: white blood cell count decreased (66.7%), neutropenia (50.0%), thrombocytopenia (50.0%), atrial fibrillation (50.0%), cardiac arrest (50.0%).

The adverse event summary separates serious adverse events, other adverse events, and deaths by regimen group. For each group, the record gives the number at risk and the number affected for serious and other events. These are descriptive summaries; they do not establish that an event was caused by treatment, and they do not provide a randomized safety comparison.

• TAC1 (10 mg Elimusertib, Biweekly 150 mg/m^2 Irinotecan): serious adverse events affected 1 of 6 at risk; other adverse events affected 6 of 6; deaths recorded: 5.
• TAC2 (20 mg Elimusertib, Biweekly 150 mg/m^2 Irinotecan): serious adverse events affected 2 of 3 at risk; other adverse events affected 3 of 3; deaths recorded: 3.
• TAC4 (20 mg Elimusertib, Weekly 25 mg/m^2 Irinotecan): serious adverse events affected 1 of 6 at risk; other adverse events affected 5 of 6; deaths recorded: 3.
• TAC5 (20 mg Elimusertib, 50 mg/m^2 Weekly Irinotecan): serious adverse events affected 4 of 6 at risk; other adverse events affected 6 of 6; deaths recorded: 5.
• TAC7 (20 mg Elimusertib, 1 mg/m^2 Topotecan): serious adverse events affected 2 of 2 at risk; other adverse events affected 2 of 2; deaths recorded: 2.
• TAC14 (20 mg Elimusertib, 1 mg/m^2 Topotecan): serious adverse events affected 1 of 6 at risk; other adverse events affected 6 of 6; deaths recorded: 4.

The record’s most frequently listed serious-event terms are white blood cell count decreased (66.7%), neutropenia (50.0%), thrombocytopenia (50.0%), atrial fibrillation (50.0%), cardiac arrest (50.0%), and pancytopenia (50.0%). The registry does not give denominators for these term-specific percentages in this summary. The groups have small and differing numbers at risk, and the summaries do not include a causal attribution for deaths.

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

The posted record describes a phase I study designed to evaluate elimusertib with irinotecan or topotecan, including a dose-escalation endpoint based on DLTs during the first treatment cycle. It also records serious and other adverse event summaries by regimen group. These details establish what the study set out to examine and what safety information is summarized in the record.

The record does not report the MTD result, DLT counts by dose level, or analyses of the listed secondary outcomes. It therefore does not support a numerical conclusion about the dose selected, response, duration of response, progression-free survival, overall survival, or pharmacokinetic exposure. The objective is not itself a result: a trial’s stated purpose cannot substitute for its observed estimates.

Nor do the safety counts show that a drug caused an event. The summaries report events and deaths, but the record does not provide causal attribution or a control group suitable for estimating comparative risk. The cohorts differ in regimen and are nonrandomized, so cross-cohort differences should not be read as evidence that one regimen is safer or less safe than another.

General: Statistical uncertainty concerns how much an estimate may vary because of the observed data and the analysis assumptions. With no posted outcome estimates or confidence intervals, the precision of efficacy or dose-finding results cannot be assessed. The adverse event counts give descriptive information, but their interpretation is constrained by the small, unequal group denominators and absence of comparative estimates.

The registry record is informative about the study framework, endpoint definition, and reported safety categories. It is not enough to establish the primary dose-finding conclusion or to make comparative claims about tumor outcomes or safety. Those conclusions would require results and methods that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because its central question is dose finding rather than a randomized efficacy comparison. The primary endpoint is an MTD defined through DLTs observed during cycle 1. That makes the event definitions, observation window, and dose-level counts central to interpreting the study. The registry supplies the DLT definition, but not the dose-level observations or the resulting MTD.

The study also combines distinct treatment schedules and drug partners. Cohort I and Cohort II use irinotecan with different schedules, while Cohort III uses topotecan. Since allocation is nonrandomized, these cohorts are not interchangeable comparison groups. This is an important distinction when reading the group-level adverse event summaries: descriptive differences cannot be treated as estimates of comparative treatment effects.

The listed outcomes span dose selection, tumor response, survival, and pharmacokinetics. That breadth illustrates why a clear hierarchy and analysis plan matter. The registry identifies the primary endpoint and lists 18 outcome measures, but records 0 analyses. It does not report multiplicity procedures, missing-data handling, analysis populations, or inferential results. Consequently, readers can distinguish the study’s planned questions from its unavailable outcome analyses, but cannot assess the full statistical evidence for them.

The planning illustrations should also be kept separate from the trial’s design. They use stated assumptions for hypothetical sample-size calculations and do not describe the actual enrollment strategy or observed power. In this nonrandomized dose-escalation setting, they cannot create a controlled comparison where the study design does not provide one.

For biostatistical interpretation, the key issue is the boundary between a well-described endpoint and a reported result. This record defines the primary toxicity rule and presents safety counts, yet does not report the dose-finding conclusion or analyses for the secondary outcomes. Recognizing that boundary prevents objectives, descriptive counts, and planning calculations from being mistaken for evidence of a treatment effect.

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.

Several limitations arise from the information available for this specific trial. The primary endpoint is defined, but the registry record does not report the observed MTD or DLT counts by dose level. Without those details, readers cannot verify how the endpoint definition was applied or assess the evidence supporting the dose-finding decision.

The study is nonrandomized, and the registry explicitly says its arms are not a like-for-like control comparison. The regimens also differ in drug partner, dose, and schedule. Any differences in outcome summaries across groups may reflect these design features or participant differences, and cannot be interpreted as causal treatment contrasts from the posted information.

The total enrollment is 29, while the serious adverse event summaries report smaller, differing numbers at risk within the regimen groups. The registry does not explain the relationship between overall enrollment and these group-specific risk sets, nor does it provide outcome-specific analysis populations. The adverse event summaries also lack confidence intervals and term-specific denominators in the listed serious-event terms.

For the secondary outcomes, no analysis estimates or methods are posted. Follow-up and censoring methods for time-to-event outcomes, response criteria, pharmacokinetic sampling details, and approaches to missing data are not reported in the registry record. Multiplicity handling and interim analyses are also not reported. These limitations constrain evaluation of precision, bias, and reproducibility; they do not show that methods were absent from the full study documentation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer — NCT04514497.
• Registry record last updated 2026-09-10; status last verified 2026-09.
• Results first posted 2026-05-19.
• 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

NCT04514497 is a Phase I, nonrandomized, unmasked, parallel study sponsored by the National Cancer Institute (NCI). It examines elimusertib combined with irinotecan or topotecan in advanced solid tumors, with a specific focus on small cell lung carcinoma, poorly differentiated neuroendocrine carcinoma, and pancreatic adenocarcinoma. The registry records enrollment of 29, a start date of 2021-10-20, a primary completion date of 2025-02-15, and an active, not recruiting status.

The primary endpoint is the maximum tolerated dose in the dose-escalation phase, defined using dose-limiting toxicities during the first cycle. Secondary outcomes include tumor response, response duration, progression-free and overall survival, and pharmacokinetic measures. The record lists 18 outcome measures and 0 analyses. It reports selected adverse event summaries, but does not report the primary endpoint result or statistical analyses of the secondary outcomes.