This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of E7046 in Subjects With Selected Advanced Malignancies (NCT02540291), a na phase 1 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02540291 |
| Phase | Phase 1 |
| Condition | Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 31 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eisai Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had selected advanced malignancies. The E7046 arm description specifies tumor types with high levels of myeloid infiltrate, based on the Cancer Genome Atlas. The record does not give further eligibility criteria in the information.
Intervention
Participants received E7046. The adverse-event results are organized by dose groups labeled 125 mg, 250 mg, 500 mg, and 750 mg. The record describes the study as open label, so treatment assignment was not masked.
Comparator
There was no concurrent control group described. The study is classified as single group, with allocation listed as not applicable. Dose groups should not be interpreted as randomized treatment and control arms or as a like-for-like comparison.
Primary question
The primary outcome asks how many participants had treatment-emergent adverse events and serious adverse events. The stated study aims were to assess safety and tolerability and to determine the maximum tolerated dose and/or recommended Phase 2 dose. The posted information does not establish comparative efficacy.
3. Trial Design
This was an open-label, multicenter Phase 1 study of E7046 in participants with selected advanced malignancies. It is classified as a single-group study, with no masking and allocation listed as not applicable. The registry describes one intervention, E7046, and gives four dose labels in the adverse-event results: 125 mg, 250 mg, 500 mg, and 750 mg. The record does not describe these dose groups as randomized arms, nor does it report a separate control group.
The enrollment was 31. The registry record gives a start date of 2015-07-30 and a primary completion date of 2018-02-27. Its current status is listed as terminated; the reason for termination is not reported in the registry record. These design and status details do not, by themselves, explain why the study ended or whether all intended study objectives were completed.
The safety population is described as the FAS, which included all participants who received at least 1 dose of study drug. The adverse-event summaries separately list participants at risk in each dose group. The registry record does not explain the relationship between the overall enrollment and the group-specific safety counts, nor does it give additional details about dose assignment, dose escalation, or the timing of changes between doses.
Objective response rate, progression-free survival, duration of response, disease control rate, and clinical benefit rate are listed as secondary outcomes. Their results are not reported in the registry record. With no concurrent comparator and no masking, the design primarily supports description of observed safety and tolerability in the enrolled participants. It does not provide a randomized estimate of how E7046 compares with another treatment.
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: A total of 31 participants with advanced malignancies were enrolled, of which 30 participants received study treatment. The study was terminated before the start of the cohort expansion part. The discontinuation of participants from study is presented in the overall study table below.
Overall Study
| Stage | E7046 125 mg | E7046 250 mg | E7046 500 mg | E7046 750 mg |
|---|---|---|---|---|
| STARTED | 8 | 8 | 7 | 7 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 8 | 8 | 7 | 7 |
Reasons for not completing this period:
| Reason | E7046 125 mg | E7046 250 mg | E7046 500 mg | E7046 750 mg |
|---|---|---|---|---|
| Death | 7 | 7 | 5 | 7 |
| Lost to Follow-up | 0 | 0 | 1 | 0 |
| Withdrawal Of Consent | 0 | 1 | 0 | 0 |
| Study Terminated By Sponsor | 1 | 0 | 0 | 0 |
| Other | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The FAS included all participants who received at least 1 dose of study drug.
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: The full analysis set (FAS) included all participants who received at least 1 dose of study drug.
| Characteristic | Unit | E7046 125 mg | E7046 250 mg | E7046 500 mg | E7046 750 mg | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 8 | 8 | 7 | 7 | 30 | |
| Age, Continuous | years | 51.3 (SD 12.15) | 53.0 (SD 17.10) | 54.4 (SD 13.40) | 64.4 (SD 10.18) | 55.5 (SD 13.82) |
| Sex: Female, Male: Female | Participants | 0 | 4 | 4 | 3 | 11 |
| Sex: Female, Male: Male | Participants | 8 | 4 | 3 | 4 | 19 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 1 | 0 | 0 | 2 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 7 | 7 | 7 | 7 | 28 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 1 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 1 | 1 | 3 |
| Race (NIH/OMB): White | Participants | 6 | 7 | 5 | 6 | 24 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 0 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 2 years).
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Its unit is participants, so the endpoint concerns how many people experienced an event category, rather than the total number of event episodes. The stated observation window runs from the first dose of study drug up to 30 days after the last dose, approximately up to 2 years.
In general, safety endpoints of this kind are used in early-phase studies to describe the types and frequency of adverse events observed during treatment and follow-up. They help characterize tolerability and can inform dose-selection decisions, which are among this study’s stated aims. Counting participants affected is clinically interpretable as a description of how many people experienced an event, but it does not convey how often events recurred in a participant, how long they lasted, or their severity unless those details are separately reported.
The posted results give serious-event and other adverse-event counts by dose group, along with selected serious-event terms. They do not give a complete narrative of event onset, duration, management, or attribution. The registry record does not report an aggregate TEAE result in the information available for this analysis.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The safety results are descriptive. In the 125 mg group, 5 participants were reported with serious adverse events and 7 with other adverse events; 8 participants were listed at risk. In the 250 mg group, the corresponding counts were 6 and 7, with 8 at risk. In the 500 mg group, the counts were 3 and 6, with 7 at risk. In the 750 mg group, the counts were 3 and 7, with 7 at risk. These counts describe what was recorded in each dose group; they are not randomized comparisons.
The registry also lists deaths by group: 7 in the 125 mg group, 7 in the 250 mg group, 5 in the 500 mg group, and 7 in the 750 mg group. The record does not state that these deaths were caused by E7046, identify their causes, or provide a comparative analysis. A death count alone cannot establish treatment attribution or explain the circumstances of each death.
Among the serious-event terms listed, ascites and dyspnoea are each reported as 25.0%. Myocardial infarction, abdominal pain, constipation, and small intestinal obstruction are each reported as 14.3%. The registry record does not report the denominator used for these percentages in the information, and these figures should not be read as rates for all enrolled participants without that denominator and a clear definition of the analysis population.
The posted information does not include effect estimates comparing doses, confidence intervals, p-values, or adjusted analyses. No statistical analyses are listed. Therefore, apparent differences among the dose-group counts should not be interpreted as evidence that one dose has a different safety profile from another. Group sizes are limited, the study lacks a concurrent control, and the record does not describe random allocation. Descriptive differences may reflect participant characteristics, exposure time, chance, or other factors that cannot be separated using the reported information.
The record’s stated goals were safety and tolerability assessment and dose selection. These goals are distinct from demonstrating a treatment effect on cancer outcomes. Although several efficacy-related secondary outcomes are named, their results are not reported in the registry record. The available figures therefore support a description of posted adverse-event counts and selected event terms, not a conclusion about comparative efficacy or causality.
9. Statistical Methods Explained
Several statistical ideas help put the posted results in context. The distinctions below are general explanations; the registry record does not report a detailed statistical analysis plan.
What does a participant count measure?
A participant count records how many people in a defined group experienced an outcome at least once. For this study, the primary outcome is framed as the number of participants with treatment-emergent adverse events and serious adverse events. This differs from an event count: one participant can experience more than one event, while a participant count treats that person as affected for the relevant category. Participant counts can be useful for an initial safety description, but they do not show recurrence, duration, timing, or intensity unless those features are reported separately.
The registry gives the number at risk and the number affected in each dose group for serious and other adverse events. These are descriptive summaries, not estimates from a model. The information does not include uncertainty intervals around the counts, and the record does not report a method for estimating such intervals. Without uncertainty estimates, readers cannot assess the statistical precision of differences between groups from these summaries alone.
Why is a single-group study different from a controlled comparison?
In general, a concurrent control group helps distinguish outcomes observed after an intervention from outcomes that might also occur without it or under another treatment. Here, the study is classified as single group, with allocation listed as not applicable. The dose-labeled groups are not described as randomized arms. Comparing their counts directly would not reproduce the protection against confounding that random allocation can provide.
Participants assigned to different dose levels can differ in ways that affect observed safety outcomes. Exposure duration, disease status, previous treatment, and other characteristics can also influence the number of events recorded. The registry record does not provide information sufficient to adjust for such differences. Accordingly, group-to-group contrasts are descriptive only and should not be treated as causal estimates of dose effects.
What would an uncertainty interval mean?
In general, a confidence interval expresses the range of values compatible with an estimate under a specified statistical model and its assumptions. A narrow interval indicates greater precision, while a wide interval indicates greater uncertainty. An interval does not guarantee that the true value lies within its bounds, and it does not resolve biases caused by study design or incomplete measurement. The registry record does not report confidence intervals for the adverse-event summaries.
A p-value, in general, measures how unusual the observed data would be under a specified null hypothesis and model. It does not measure the probability that a treatment is effective or safe, and it does not describe the size or clinical importance of an effect. No p-values or inferential analyses are reported in the registry record, so the posted counts should not be presented as statistically significant or nonsignificant findings.
How should event percentages be understood?
A percentage is interpretable only when its denominator and population are clear. The serious-event terms are listed with percentages, but the denominator for those term-specific percentages is not reported in the registry record. The percentages therefore describe the registry’s displayed summaries without establishing the risk among all participants, the risk within a particular dose group, or the risk over a common exposure period.
In general, unequal time receiving study drug can affect opportunities for an adverse event to be observed. A participant followed longer has more time in which an event might be recorded. Exposure-adjusted rates or time-to-event methods can address some questions about differing observation time, but they require appropriate data and a stated analysis. The registry record does not report such analyses for the outcomes.
What do the dose labels and sample-size calculations imply?
The dose labels identify the groups used in the posted safety summaries. They do not establish that participants were randomly assigned, that every participant received the same duration of exposure, or that the groups are exchangeable. Those details are not reported in the registry record.
In general, a sample-size calculation is a planning exercise based on assumptions about the outcome, target effect, allocation, and statistical procedure. It is not a measurement of how much power a completed study actually had. Any planning illustration framed as a two-arm comparison is especially distinct from this single-group design: it cannot turn the observed dose groups into randomized treatment and control arms. The registry record does not report a sample-size justification or a statistical plan for the trial itself.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists eight outcome measures and names objective response rate, progression-free survival, duration of response, disease control rate, and clinical benefit rate as secondary outcomes. The primary outcome is the number of participants with TEAEs and SAEs. The record does not report a testing hierarchy, a family-wise error strategy, or another approach for handling multiple outcome comparisons. It also lists no statistical analyses.
In general, examining multiple outcomes or multiple time points increases the chance of finding an apparently notable result by chance if each is assessed independently. A prespecified hierarchy or multiplicity adjustment can help control this issue when formal hypothesis tests are planned. Without a reported plan and analysis, no claim about statistical significance across the outcomes can be evaluated. The named secondary outcomes are not accompanied by results in the registry record.
The stated analysis population for the primary outcome is the FAS, including all participants who received at least 1 dose of study drug. The registry record does not describe how missing safety observations were handled, how participants with incomplete follow-up were treated, or whether any imputation was used. It does not report the extent or pattern of missing outcome data. These details matter because incomplete follow-up can affect the opportunity to observe adverse events.
The registry record also does not report whether outcome definitions or analysis methods changed over time, whether any analyses were interim, or how deviations from the intended study procedures were handled. Those items should not be inferred from the study’s Phase 1 label or its stated objectives.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| E7046 125 mg | 5 | 8 | 62.5% |
| E7046 250 mg | 6 | 8 | 75.0% |
| E7046 500 mg | 3 | 7 | 42.9% |
| E7046 750 mg | 3 | 7 | 42.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| E7046 125 mg | 7 of 8 |
| E7046 250 mg | 7 of 8 |
| E7046 500 mg | 5 of 7 |
| E7046 750 mg | 7 of 7 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| E7046 125 mg | 7 of 8 |
| E7046 250 mg | 7 of 8 |
| E7046 500 mg | 6 of 7 |
| E7046 750 mg | 7 of 7 |
Most frequent serious adverse event terms
| Event term | Organ system | E7046 125 mg | E7046 250 mg | E7046 500 mg | E7046 750 mg |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | 0 of 8 | 1 of 8 | 0 of 7 | 1 of 7 |
| Ascites | Gastrointestinal disorders | 0 of 8 | 2 of 8 | 0 of 7 | 0 of 7 |
| Small intestinal obstruction | Gastrointestinal disorders | 1 of 8 | 0 of 8 | 0 of 7 | 1 of 7 |
| Pyrexia | General disorders | 0 of 8 | 1 of 8 | 1 of 7 | 0 of 7 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 0 of 8 | 2 of 8 | 0 of 7 | 0 of 7 |
| Cardiopulmonary failure | Cardiac disorders | 1 of 8 | 0 of 8 | 0 of 7 | 0 of 7 |
| Myocardial infarction | Cardiac disorders | 0 of 8 | 0 of 8 | 0 of 7 | 1 of 7 |
| Constipation | Gastrointestinal disorders | 0 of 8 | 0 of 8 | 1 of 7 | 0 of 7 |
| Duodenal stenosis | Gastrointestinal disorders | 0 of 8 | 1 of 8 | 0 of 7 | 0 of 7 |
| Large intestinal obstruction | Gastrointestinal disorders | 1 of 8 | 0 of 8 | 0 of 7 | 0 of 7 |
Most frequent non-serious adverse event terms
| Event term | Organ system | E7046 125 mg | E7046 250 mg | E7046 500 mg | E7046 750 mg |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 2 of 8 | 2 of 8 | 3 of 7 | 3 of 7 |
| Fatigue | General disorders | 1 of 8 | 3 of 8 | 3 of 7 | 3 of 7 |
| Nausea | Gastrointestinal disorders | 0 of 8 | 3 of 8 | 3 of 7 | 3 of 7 |
| Anaemia | Blood and lymphatic system disorders | 2 of 8 | 1 of 8 | 3 of 7 | 1 of 7 |
| Decreased appetite | Metabolism and nutrition disorders | 2 of 8 | 2 of 8 | 2 of 7 | 1 of 7 |
| Vomiting | Gastrointestinal disorders | 1 of 8 | 2 of 8 | 1 of 7 | 2 of 7 |
| Dehydration | Metabolism and nutrition disorders | 0 of 8 | 1 of 8 | 1 of 7 | 2 of 7 |
| Headache | Nervous system disorders | 0 of 8 | 3 of 8 | 1 of 7 | 0 of 7 |
| Abdominal pain | Gastrointestinal disorders | 0 of 8 | 2 of 8 | 1 of 7 | 0 of 7 |
| Weight decreased | Investigations | 0 of 8 | 2 of 8 | 0 of 7 | 1 of 7 |
Serious events with the highest arm-level rate: ascites (25.0%), dyspnoea (25.0%), myocardial infarction (14.3%), abdominal pain (14.3%), constipation (14.3%).
The serious adverse event counts are 5 of 8 at risk in the 125 mg group, 6 of 8 in the 250 mg group, 3 of 7 in the 500 mg group, and 3 of 7 in the 750 mg group. Counts for other adverse events are 7 of 8, 7 of 8, 6 of 7, and 7 of 7, respectively. These are participants affected, not counts of individual event episodes. The registry record does not clarify whether “other” refers to a particular severity category, so it should not automatically be treated as synonymous with non-serious.
The listed deaths are 7, 7, 5, and 7 across the same dose groups. The record does not report their causes or establish that they were treatment-related. Likewise, the serious-event terms and percentages are descriptive listings; the denominator for those percentages is not reported in the registry record. These figures do not establish comparative risk, causation, or a dose-response pattern.
In general, interpreting safety requires attention to event definitions, follow-up time, exposure, and attribution. The stated safety window extends from the first dose to 30 days after the last dose, approximately up to 2 years, but group-specific exposure and follow-up are not reported.
12. What the Result Does, and Does Not, Mean
The posted results show that participants in each dose group were recorded with serious adverse events and other adverse events, and that deaths were recorded in each group. The serious-event summaries also identify several event terms with listed percentages. These are observations from the registry record, not a complete account of each participant’s clinical course.
Counts of affected participants answer a limited question: how many people in the recorded group had at least one event in the stated category. They do not show the number of episodes, the duration or severity of each event, whether multiple events occurred in the same person, or the timing of events relative to dosing. The record does not provide enough detail to interpret the listed deaths as caused by study drug, and it does not report an attribution analysis.
The study was single group and open label, with no randomized comparator described. Therefore, the posted information does not estimate what would have happened to similar participants under another treatment or without E7046. Differences in counts across the dose labels cannot establish that dose caused a difference in risk. The record also does not report inferential analyses that would quantify uncertainty in such comparisons.
The study’s stated aims concerned safety, tolerability, and dose selection. The listed secondary outcomes concern response and disease control, but their results are not reported in the registry record. The safety summaries therefore do not demonstrate whether E7046 affects tumor response or progression. Nor do they establish a final maximum tolerated dose or recommended Phase 2 dose from the information.
In general, an early-phase safety description can contribute to understanding what events were observed during a study, while leaving substantial uncertainty about causal relationships and comparative risks. The posted counts are best read in that descriptive scope. They should not be expanded into a claim that the intervention is effective, ineffective, safe, or unsafe.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the limits and uses of descriptive safety reporting in an early-phase, single-group study. Its primary outcome is framed as a count of participants with treatment-emergent and serious adverse events, matching the stated emphasis on safety and tolerability. The posted group-level counts make the event summaries concrete, while the absence of a concurrent control limits causal interpretation.
The design distinction matters. Dose groups can organize a safety summary, but dose labels alone do not create a valid randomized comparison. Without random allocation and a reported plan for adjustment, observed differences may reflect factors other than dose. The registry record does not provide enough information to separate these possibilities.
The record also illustrates why denominators and outcome definitions are essential. The group summaries state how many participants were at risk and how many were affected, while selected serious-event terms are listed as percentages without a reported denominator in the information available. A clear denominator, follow-up description, and event definition are needed to judge how broadly each figure applies.
Finally, the separation between an outcome being named and its result being reported is important. The record lists several secondary outcomes but does not report their results or statistical analyses. Readers should distinguish study aims and registered outcome labels from evidence actually presented. The resulting interpretation remains focused on descriptive safety observations rather than efficacy claims or formal comparisons.
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 detailed eligibility criteria beyond the description of selected advanced malignancies and tumor types with high myeloid infiltrate based on the Cancer Genome Atlas. The characteristics of participants in each dose group, including disease and prior-treatment details, are not reported in the information available for this analysis. This limits assessment of how representative the groups were or whether they differed in clinically relevant ways.
The study is open label and single group, with no randomized comparator described. Dose groups therefore cannot be treated as controlled arms. The record does not explain dose assignment, the sequence of dosing decisions, group-specific duration of exposure, or the reason for termination. It also does not report the causes or treatment attribution of deaths.
The primary outcome is described as a count of participants with TEAEs and SAEs, but the posted adverse-event summary does not provide a complete aggregate TEAE result in the information. The definition of “other” adverse events, the denominator for serious-event term percentages, and detailed event-level information are not reported in the registry record. Missing-data handling, follow-up completeness, and an analysis plan are also not reported.
No inferential analyses, confidence intervals, or p-values are listed. The named secondary efficacy outcomes do not have reported results. These gaps prevent estimation of comparative effects and limit assessment of precision, multiplicity, and the relationship between observed events and E7046 exposure.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of E7046 in Subjects With Selected Advanced Malignancies — NCT02540291.
- Registry record last updated 2020-02-17; status last verified 2018-07.
- Results first posted 2020-02-17.
- 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.
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18. Record Summary
NCT02540291 is an open-label, multicenter Phase 1 study of E7046 in selected advanced malignancies. The registry classifies it as single group, with allocation not applicable and no masking. Enrollment was 31; the recorded start date was 2015-07-30, primary completion was 2018-02-27, and status is terminated.
The primary outcome concerns participants with treatment-emergent and serious adverse events. Safety counts are reported by dose group, along with selected serious-event terms and deaths. The record lists response and disease-control outcomes as secondary measures, but their results and statistical analyses are not reported in the registry record. The available evidence is descriptive and does not provide a randomized comparison or an estimate of comparative efficacy.