A Study of ONO-7475 in Patients With Acute Leukemias: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of ONO-7475 in Patients With Acute Leukemias (NCT03176277), a non-randomized phase 1, phase 2 study. The primary outcome is Incidence of Adverse Events (Part A).

2. Clinical Question

This is an early-phase safety question rather than a randomized test of treatment benefit. The record’s primary outcome asks how many participants experienced specified adverse events during the stated safety follow-up. It does not, by itself, estimate what would have happened to similar participants without ONO-7475 or with another treatment.

The listed intervention groups represent different dose levels and a combination regimen. Because participants were not randomly allocated, comparisons across these groups may reflect differences in who entered each part, the timing or circumstances of treatment, or other factors, as well as any dose-related differences. The registry record does not report enough information to establish how the groups were formed or whether they were intended for formal comparative analysis.

The clinical question also has boundaries. The updated summary describes specific relapsed or refractory populations, whereas the conditions field uses the broader labels acute leukemia and myelodysplastic syndromes. The record does not report detailed eligibility criteria here, so the precise clinical characteristics of enrolled participants cannot be reconstructed from these summaries alone.

3. Trial Design

The registry record describes a phase I/II, open-label study of ONO-7475 in patients with acute leukemias or myelodysplastic syndromes. Ono Pharmaceutical Co., Ltd. is named as sponsor. The record lists enrollment of 42 and classifies the study as non-randomized, with no masking and a single-group model. Its status is terminated. The listed start date is 2017-06-26 and the primary completion date is 2022-12-01.

Part A included ONO-7475 once daily at 3mg, 6mg, and 10mg. Part D listed ONO-7475 6mg with venetoclax (70-400mg). These descriptions show that the study examined more than one regimen. They do not establish that every participant could receive each regimen, that participants moved between dose levels, or that the groups were comparable. Those details are not reported in the registry record.

Open-label means the study was not masked, so treatment assignment was not concealed from participants and investigators in the way it would be in a blinded study. Non-randomized means assignment was not described as random. General statistical context: without random allocation, comparisons between groups are more vulnerable to differences in participant characteristics and treatment circumstances. The listed arms should therefore not be read as randomized treatment-versus-control groups.

The stated primary endpoint applies to Part A and concerns adverse events. Other listed outcomes include dose-limiting toxicities and maximum tolerated dose, pharmacokinetic measures, pharmacodynamic measures, overall response rate, and duration of response. These outcomes address different aspects of early clinical evaluation; their presence in the outcomes list does not mean that their results are available.

The record does not report the reason for termination, the planned enrollment rationale, a sample-size justification, detailed dose-escalation rules, interim analyses, or a complete statistical analysis plan. It also does not report a control arm. These absences limit what can be inferred about the intended statistical design and the interpretation of differences among regimens.

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: Part A study: a total of 29 participants signed informed consent form and were enrolled in the study. 9 participants were screen failures who did not meet eligibility criteria. 20 participants received at least 1 dose of study drug. Part D study: a total of 33 participants signed informed consent form and were enrolled in the study. 11 participants were screen failures who did not meet eligibility criteria. 22 participants received at least 1 dose of study drug. No dose escalation conducted.

Part A Dose Escalation Study

Reasons for not completing this period:

Part D ONO-7475 6mg + Venetoclax

Analysis population for the primary outcome, as defined in the registry: Safety analysis set, in participants who received at least 1 dose of ONO-7475.

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: Full analysis set, respective of Part A and Part D study.

6. Primary Endpoint

The registry lists the primary outcome as Incidence of Adverse Events (Part A), measured over From start of study drug up to 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first (maximum of 32 months)..

The primary endpoint is the incidence of the most common treatment-emergent adverse events of CTCAE grade 3 or higher in Part A. The registry description defines “most common” as a frequency of >20% and says events are coded by preferred term using MedDRA version 23.1. Severity is classified using CTCAE version 4.03. The endpoint is expressed as a count of participants, and the stated population is the safety analysis set: participants who received at least 1 dose of ONO-7475.

The follow-up window begins with study-drug initiation and ends 30 days after permanent discontinuation of study drug or initiation of new anti-cancer therapy, whichever occurs first, with a maximum of 32 months. This window matters because an adverse-event count depends on the period in which events are observed. It is not a count of events over an unlimited period.

General statistical context: an incidence endpoint summarizes how many people experienced an event, rather than how many separate episodes occurred. Counting participants can make safety findings easier to describe, but it does not convey every detail of event timing, duration, recurrence, or severity within a grade category. A count also needs its denominator and follow-up context to be interpreted appropriately.

This endpoint is used in an early-phase study to characterize safety and tolerability. It does not establish comparative risk because the record does not describe random assignment to a control group. The registry record lists aggregate serious and other adverse-event figures, but it does not provide the complete primary endpoint results by preferred term in the information. Thus, those figures should not be mistaken for a full presentation of the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint tell us?

The primary outcome is a count of participants experiencing treatment-emergent adverse events meeting the specified severity and frequency criteria. General statistical explanation: a participant count identifies how many people had an event; it is different from an event count, which could include repeated events for the same person. Counts are often useful for describing safety, but their interpretation depends on the population observed, the event definition, and the follow-up window.

Here, the safety analysis set includes participants who received at least 1 dose of ONO-7475. The endpoint window extends from starting study drug through 30 days after permanent discontinuation or initiation of new anti-cancer therapy, whichever occurs first, subject to a maximum of 32 months. Participants may therefore have different actual observation periods. The registry record does not report the distribution of follow-up time or how incomplete follow-up was handled.

The primary outcome description refers to events occurring with frequency >20% and CTCAE grade 3 or higher. CTCAE provides a framework for classifying adverse-event severity, while MedDRA provides coded terms for describing events. General statistical explanation: consistent coding and grading make safety information more structured, but they do not remove the need to consider event definitions, exposure time, and the number of participants observed. The record’s stated versions are CTCAE version 4.03 and MedDRA version 23.1.

Why is the design important?

This study is listed as non-randomized and open-label. General statistical explanation: random allocation can help balance measured and unmeasured characteristics across comparison groups on average. In a non-randomized study, the groups may differ for reasons related to enrollment, clinical status, treatment sequence, or other factors. Open-label treatment can also affect care, observation, or reporting. These considerations are reasons for caution when reading between-group differences; they do not show that any particular bias occurred.

The registry also classifies the model as single-group, while listing dose groups for Part A and a combination group for Part D. The record does not explain the allocation process or how the listed groups relate to one another analytically. As a result, it is safest to describe the reported groups individually rather than treating them as controlled comparisons.

What does a confidence interval mean?

General explanation: a confidence interval expresses the uncertainty of an estimate under a specified statistical model and sampling procedure. A narrower interval generally indicates greater statistical precision, while a wider interval indicates less precision. The registry information does not report confidence intervals for the adverse-event counts. The counts should therefore not be presented as if they had a stated interval of precision.

General explanation: over-dispersion matters when observed variability is greater than a statistical model assumes. If a model assumes that outcomes vary less than they actually do, its uncertainty estimates may be too optimistic. Whether over-dispersion is relevant depends on the outcome and model. The registry record does not report a model-based analysis of the primary endpoint or a plan addressing over-dispersion, so no such adjustment can be attributed to this study.

How should the other listed outcomes be read?

The secondary outcomes include dose-limiting toxicities and determination of maximum tolerated dose, along with pharmacokinetic measures such as Cmax, Ctrough, Tmax, AUC, and T1/2, a food-effect assessment, and pharmacodynamic assessment of Axl and Mer inhibition. Overall response rate and duration of response are also listed for ONO-7475 groups in Part A. General statistical explanation: these outcome types answer different questions. Safety events describe harms; pharmacokinetic outcomes describe drug concentrations over time; pharmacodynamic outcomes concern biological activity; and response outcomes describe clinical tumor response under their definitions.

Listing an outcome does not show its result, the analysis population used, or the statistical method applied. The registry record does not report the results for these listed outcomes in the information. It also does not report an analysis plan specifying which outcomes were confirmatory, how estimates were constructed, or how missing observations were handled.

What do planning illustrations mean?

General explanation: a sample-size illustration based on an observed effect is a hypothetical planning exercise. It asks how many participants per arm might be needed under stated assumptions to detect an effect of a chosen size, significance level, allocation, and statistical approximation. Such an illustration is not the number actually enrolled, does not explain the trial’s original design, and is not observed power. The registry record does not report the study’s sample-size justification or the assumptions used in its original planning.

For this study, the design is not a randomized two-arm comparison, so planning illustrations framed around equal allocation between arms should not be interpreted as describing the actual trial design. They are conditional calculations, not a retrospective test of whether the study was “powered.” The record does not report a formal comparative effect estimate for the safety outcome to support a definitive comparative interpretation.

What can the reported analyses establish?

The summarized record lists no analyses. This does not erase the descriptive safety counts that are posted, but it means that no inferential analysis is reported for those counts. General statistical explanation: descriptive summaries show what was observed in the reported study groups; inferential analyses use a specified model to quantify uncertainty or test a stated comparison. The latter require an analysis population, outcome definition, assumptions, and a prespecified or otherwise documented approach.

Overall, the methods context supports careful description rather than causal comparison. Counts, group labels, endpoint definitions, and follow-up should be read together. The record does not report enough detail to reconstruct participant-level analyses, assess all model assumptions, or determine how all protocol-level decisions were made.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists many outcomes: the primary adverse-event endpoint, dose-limiting toxicities and maximum tolerated dose, several pharmacokinetic measures, food effect, pharmacodynamics, overall response rate, duration of response, and additional outcomes reflected in the outcome-measure count. When many outcomes are examined, the chance of finding an apparently notable result by chance can increase if multiple statistical tests are conducted. General statistical context: multiplicity procedures can control or describe this issue, but the appropriate approach depends on the study’s goals and analysis plan.

A multiplicity adjustment or hierarchy is not reported in the registry record. The record also does not report which outcomes, if any, were designated confirmatory, whether interim analyses were conducted, or how analyses were selected for reporting. Those details should not be inferred from the phase label or the outcomes list.

The primary endpoint population is stated as participants who received at least 1 dose of ONO-7475. The record does not report how missing outcome data, incomplete follow-up, withdrawals, or participants with partial observation were handled. Nor does the summarized information report participant-level denominators for every outcome and time point. Missing-data methods are important because participants with incomplete follow-up may have different opportunities for events to be observed.

The record lists 42 enrolled participants, but that enrollment figure alone does not establish the number included in each outcome analysis. The reported group-specific at-risk counts are available for the safety figures, while the analysis population and missing-data handling for other outcomes are not reported in the registry record. The posted information therefore does not support reconstruction of a complete analysis set across all endpoints.

These gaps do not imply that a particular method was or was not used outside the record. They define the limits of what can be checked from the registry information.

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: febrile neutropenia (57.1%), pneumonia (33.3%), sepsis (33.3%), influenza (33.3%), leukocytosis (33.3%).

The posted serious adverse-event figures are counts within the listed groups. For ONO-7475 3mg, 9 participants were affected among 10 at risk; for ONO-7475 6mg, 2 among 3; for ONO-7475 10mg, 6 among 7; and for ONO-7475 6mg with venetoclax, 13 among 22. The other adverse-event counts listed are 10 among 10, 3 among 3, 7 among 7, and 21 among 22, respectively. The record also lists deaths as 10, 3, 5, and 15 in those groups.

These are descriptive figures, not adjusted comparisons. The groups are non-randomized and their at-risk counts differ. A simple visual comparison can therefore be misleading: it may reflect group composition or observation as well as treatment. The record does not report a comparative statistical analysis or explain the causes of the listed deaths.

The serious adverse-event terms include febrile neutropenia (57.1%), pneumonia (33.3%), sepsis (33.3%), influenza (33.3%), leukocytosis (33.3%), and Klebsiella bacteraemia (20.0%). Terms can occur in the same participant, so these percentages should not be summed or interpreted as mutually exclusive categories. Their denominators and overlap are not further detailed in the summarized record.

General statistical context: safety counts are most informative when considered alongside definitions, denominators, exposure duration, and uncertainty. The registry record gives the primary endpoint’s observation window, but the summarized serious-event figures do not provide a full account of event timing or participant-level patterns.

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

The record documents a phase I/II, open-label study that examined ONO-7475 in several regimens, including monotherapy dose groups and a combination with venetoclax. It states that the Part A primary endpoint concerns the incidence of common treatment-emergent adverse events of CTCAE grade 3 or higher. It also posts group-level counts for serious and other adverse events and deaths, along with selected serious adverse-event terms.

Those observations describe what the registry reports for the listed study groups. They do not establish that ONO-7475 caused every event or death, and the record does not report attribution analyses. They also do not establish that one dose or regimen is safer than another. The absence of randomization and the lack of a reported comparative analysis prevent a like-for-like treatment comparison.

The record lists preliminary efficacy outcomes, including overall response rate and duration of response, but their results are not reported in the registry record. Accordingly, this page cannot conclude whether a regimen improved response, delayed progression, or changed survival. It also cannot infer that an unreported result was favorable or unfavorable.

General statistical context: an observed count is not a complete measure of certainty. Precision depends on the number observed, the underlying variability, the observation period, and the analysis method. Since confidence intervals and inferential analyses for the listed safety counts are not reported, the counts should not be read as precise estimates of event frequency in a broader population.

The study’s terminated status is recorded, but the reason for termination is not reported in the registry record. The status alone does not identify why the study ended or indicate whether any particular result drove that decision. Similarly, enrollment of 42 does not show that the original sample-size target was met, since a planned target and its justification are not reported.

The appropriate conclusion is therefore limited: the registry provides descriptive safety information for a small, non-randomized early-phase study and lists a broader set of safety, pharmacology, and response questions. It does not provide a randomized estimate of treatment benefit or a definitive comparison of harms across regimens.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it places several dose regimens and a combination regimen within an early-phase study, while the registry classifies the design as non-randomized and single-group. That combination makes it important to distinguish descriptive arm summaries from controlled comparisons. The mere presence of multiple groups does not create the balance or interpretability of randomized assignment.

The primary outcome also illustrates the need to keep endpoint definitions precise. It concerns participants with common treatment-emergent adverse events at CTCAE grade 3 or higher, in a defined safety population and observation window. The separately posted serious adverse-event figures are relevant safety information, but they should not be treated as a complete substitute for the specified primary endpoint results. Endpoint labels, event definitions, and analysis populations all matter.

The record highlights another general lesson: outcome lists and outcome results are not the same thing. Pharmacokinetic, pharmacodynamic, response, and safety outcomes are all listed, but results are not reported for many of those questions in the information. Statistical interpretation must follow the analyses actually reported, not the breadth of the original study aims.

Finally, the group sizes differ, and some are small. General statistical context: estimates based on limited observations are vulnerable to substantial sampling variability. This makes uncertainty and the design especially important, but the registry record does not report confidence intervals or a comparative analysis for the safety counts. Clear description, restraint about causal claims, and attention to what remains unreported are central to reading this trial statistically.

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 registry record does not report the reason for termination. Without that information, the status cannot be interpreted as evidence about the study’s safety findings, efficacy findings, feasibility, or other circumstances.

The record’s group descriptions and overall design classification do not fully explain how participants entered Part A or Part D, how dose levels were selected, whether participants could transition between regimens, or whether any groups were intended for direct comparison. The absence of randomization means group-level contrasts may be confounded by differences in participants or study circumstances.

The summarized safety information is limited to event counts and selected serious adverse-event terms. It does not provide individual-level data, event timing, duration, recurrence, attribution, or a complete breakdown by preferred term for the primary endpoint. The record does not report confidence intervals or comparative tests for these figures.

The record lists deaths within each group, but causes and treatment attribution are not reported in the information. The listed deaths therefore cannot be interpreted as treatment-related mortality. Likewise, the selected serious adverse-event percentages do not establish that terms are mutually exclusive or that they share a denominator.

The registry record does not report the sample-size justification, detailed analysis plan, multiplicity strategy, interim analyses, handling of missing data, or reason for study termination. Results for the listed response, pharmacokinetic, and pharmacodynamic outcomes are not reported in the summarized record. These limitations restrict both reproducibility and the scope of conclusions that can be drawn from the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of ONO-7475 in Patients With Acute Leukemias — NCT03176277.
• Registry record last updated 2024-07-15; status last verified 2024-07.
• Results first posted 2024-05-16.
• 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

This registry record describes a phase I/II, open-label, non-randomized study of ONO-7475 in acute leukemias or myelodysplastic syndromes. It lists enrollment of 42, with ONO-7475 monotherapy dose groups in Part A and ONO-7475 with venetoclax in Part D. The study is recorded as terminated.

The Part A primary endpoint concerns common treatment-emergent adverse events of CTCAE grade 3 or higher among participants who received at least 1 dose of ONO-7475. The record posts group-level safety counts and selected serious adverse-event terms. It also lists dose-limiting toxicity, pharmacokinetic, pharmacodynamic, and response outcomes.

The posted information does not report a randomized comparator, comparative analyses, or the results of the listed efficacy outcomes. The reason for termination, sample-size justification, missing-data approach, and detailed statistical analysis plan are not reported in the registry record. The safety figures are therefore best read descriptively, without treating them as causal or comparative evidence.