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 MEN1703 (SEL24) in Participants With Acute Myeloid Leukemia (NCT03008187), a non-randomized phase 1, phase 2 study. The primary outcome is Part 1 and Part 2: Number of Participants Experiencing Treatment-emergent Adverse Events.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03008187 |
| Phase | Phase 1, Phase 2 |
| Condition | Acute Myeloid Leukemia |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 73 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Menarini Group |
| Results posted | Yes |
2. Clinical Question
Population
Participants with acute myeloid leukemia (AML) were enrolled. The primary endpoint’s stated safety population includes participants who received at least 1 dose of MEN1703. The registry record does not report further eligibility criteria in the information available for this analysis.
Intervention
Participants received MEN1703 orally in dose cohorts. The listed doses were 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, and 150 mg, given once daily for 14 consecutive days in cycles of 21 days.
Comparator
There was no randomized control group. This was a non-randomized, single-group study with no masking. The dose cohorts describe treatment groups, but they are not a like-for-like control comparison.
Primary question
The primary endpoint asks how many participants experienced treatment-emergent adverse events during follow-up of up to 21 months. The study’s stated purpose was to identify the maximum tolerated dose and further investigate the safety profile of MEN1703. The registry record does not report the maximum tolerated dose as a result in the information analyzed.
3. Trial Design
This completed Phase I/II study evaluated MEN1703 in participants with AML. The registry record lists an enrollment of 73 and identifies Menarini Group as the sponsor. The recorded start date is 2017-03-10, and the primary completion date is 2023-04-13.
The study was non-randomized, unmasked, and described as a single-group model. Participants were assigned to dose cohorts rather than randomized between MEN1703 and a control treatment. The six listed cohorts received 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, or 150 mg of MEN1703 orally once daily for 14 consecutive days in cycles of 21 days. The registry record does not provide details of the rules used to move between dose cohorts, nor does it report a control intervention.
The stated purpose was to identify the maximum tolerated dose and further investigate safety. The primary endpoint was the number of participants experiencing treatment-emergent adverse events, with a timeframe of up to 21 months. The listed secondary outcomes include overall response rate, partial remission rate, duration of response, relapse-free survival, overall survival, event-free survival, transfusion conversion rate, and transfusion maintenance rate.
Because participants were not randomized to a control group, differences between dose cohorts cannot be interpreted as controlled treatment effects. Cohorts may differ in participant characteristics, follow-up, or other factors, and the registry record does not report information that would establish comparability. The record does not report the planned sample-size rationale or the statistical plan for comparing cohorts.
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.
Part 1: Dose Escalation
| Stage | Cohort 1 (25 mg) | Cohort 2 (50 mg) | Cohort 3 (75 mg) | Cohort 4 (100 mg) | Cohort 5 (125 mg) | Cohort 6 (150 mg) |
|---|---|---|---|---|---|---|
| STARTED | 2 | 3 | 3 | 6 | 7 | 4 |
| Received at Least 1 Dose of Study Drug | 2 | 3 | 3 | 6 | 7 | 4 |
| COMPLETED | 2 | 3 | 3 | 6 | 7 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Part 2: Dose Expansion
| Stage | Cohort 1 (25 mg) | Cohort 2 (50 mg) | Cohort 3 (75 mg) | Cohort 4 (100 mg) | Cohort 5 (125 mg) | Cohort 6 (150 mg) |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 48 | 0 |
| Received at Least 1 Dose of Study Drug | 0 | 0 | 0 | 0 | 48 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 48 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety population: all participants that received at least 1 dose of MEN1703.
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: Safety population: all participants who received at least 1 dose of MEN1703.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Cohort 1 (25 mg) | Cohort 2 (50 mg) | Cohort 3 (75 mg) | Cohort 4 (100 mg) | Cohort 5 (125 mg) | Cohort 6 (150 mg) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 2 | 3 | 3 | 6 | 55 | 4 | |
| Age, Continuous | years | 47.50 (SD 31.820) | 71.00 (SD 5.000) | 75.33 (SD 8.963) | 65.67 (SD 18.726) | 65.55 (SD 12.060) | 63.50 (SD 7.047) |
| Sex: Female, Male: Female | Participants | 1 | 2 | 2 | 3 | 24 | 1 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 1 | 3 | 31 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 2 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 3 | 3 | 6 | 53 | 4 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 0 | 0 | 2 | 1 | 0 |
| Race (NIH/OMB): White | Participants | 1 | 3 | 3 | 4 | 51 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 | 2 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Part 1 and Part 2: Number of Participants Experiencing Treatment-emergent Adverse Events, measured over Up to 21 months.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants who experienced treatment-emergent adverse events. An adverse event was defined as a new untoward medical occurrence or worsening of a pre-existing medical condition after a participant received a medicinal product. The definition does not require that the event be caused by the study treatment. It includes unfavorable signs, symptoms, diseases, and clinically significant laboratory findings temporally associated with use of the investigational product, whether or not considered related to it.
A participant count is a straightforward safety summary: it describes how many people in the defined safety population experienced an event during the stated timeframe. This measure is useful for describing the extent of reported safety events in a dose-finding study. It does not, by itself, indicate how many separate events occurred, how severe each event was, or whether MEN1703 caused the events.
The endpoint timeframe is up to 21 months, and the stated safety population consists of participants who received at least 1 dose of MEN1703. The registry record’s description directs readers to the reported adverse events module for summaries of serious and all other non-serious adverse events regardless of causality. The endpoint result itself is not reported in the registry record in the information analyzed here, so the overall number meeting this primary endpoint cannot be described from that record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies treatment-emergent adverse events as the primary endpoint, but it does not report a result for that endpoint in the information analyzed. The safety summaries do provide counts by dose cohort for participants at risk and participants affected by serious and other adverse events, together with deaths. These descriptive counts should not be treated as an estimate of a causal treatment effect.
For serious adverse events, the posted cohort counts are 0 of 2 in Cohort 1 (25 mg), 0 of 3 in Cohort 2 (50 mg), 3 of 3 in Cohort 3 (75 mg), 6 of 6 in Cohort 4 (100 mg), 35 of 55 in Cohort 5 (125 mg), and 4 of 4 in Cohort 6 (150 mg). For other adverse events, the counts are 2 of 2, 3 of 3, 3 of 3, 6 of 6, 52 of 55, and 4 of 4, respectively. The registry record reports deaths by cohort as 2, 3, 3, 1, 35, and 4, respectively. These are cohort-level descriptive summaries; they do not establish why an event or death occurred.
The serious-event terms listed most prominently include febrile neutropenia at 66.7%, and bacteraemia, pneumonia, sepsis, urinary tract infection, and fall at 33.3% each. The record does not give the denominators or further event-level details alongside these percentages in the information analyzed. The percentages therefore should be read as registry-reported summaries, not as a basis for reconstructing counts or making comparisons between cohorts.
Although the cohort summaries are presented separately by dose, the study was non-randomized and had no control group. Cohort size and reported event counts vary, and participants in different cohorts cannot be assumed comparable. A pattern across dose groups would not, on its own, show that dose caused a change in risk. The registry record does not report adjusted comparisons, confidence intervals, or inferential analyses; it lists zero analyses. The posted results support a descriptive account of recorded events, but not a controlled estimate of relative safety or efficacy.
9. Statistical Methods Explained
The primary endpoint is a count of participants experiencing treatment-emergent adverse events, rather than a continuous measurement. For a count endpoint of this kind, the basic descriptive result is the number of participants meeting the event definition within the stated analysis population. The registry record defines that population as participants who received at least 1 dose of MEN1703. The endpoint timeframe is up to 21 months.
What does a participant count represent?
A participant count indicates whether people in the analysis population experienced an event during follow-up. It is different from a count of all events: one participant could experience more than one adverse event. The primary endpoint’s wording focuses on participants, while the adverse event summaries separately report participants at risk and participants affected. Those summaries should not be read as a count of every event episode.
The adverse event definition is broad and does not require a causal relationship with treatment. It includes an occurrence or worsening of a medical condition and may include a symptom, sign, disease, or clinically significant laboratory finding. Thus, an event recorded after treatment is not automatically an event caused by treatment. The registry record indicates that the adverse event summaries include events regardless of causality.
How should cohort summaries be read?
The registry record separates safety results by dose cohort. A cohort-level count describes the participants recorded as affected within that cohort; it is not a randomized comparison. In general, randomization helps balance measured and unmeasured participant characteristics across treatment groups. Without randomization or a control group, differences between cohorts may reflect differences in participants, follow-up, or other circumstances as well as any possible dose relationship. The registry record does not report adjustments that would address these issues.
General statistical principle: a confidence interval expresses uncertainty around an estimate under the assumptions of the method used. It is useful because a point estimate alone does not show how precise the estimate is. The registry record does not report confidence intervals for the safety counts in the information analyzed here, so their statistical precision cannot be assessed from interval estimates.
What can planning calculations tell a reader?
General statistical principle: sample-size calculations are planning tools. They describe the amount of information a proposed study might need to detect a prespecified effect under chosen assumptions. They are not observed outcomes, and they are not observed power. The planning assumptions associated with the posted illustration specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event calculations, the illustration uses a total number of events; other calculations are expressed as participants per arm.
Those assumptions describe the calculation, not the design of this trial. The study itself was non-randomized and single-group, and the record does not report a planned sample-size justification. A planning comparison between two arms cannot turn the dose cohorts into randomized comparator arms. Any planning values should be understood as hypothetical design illustrations rather than evidence about what the study observed or the power it achieved.
What is not available for inferential interpretation?
The registry record lists 15 outcome measures and zero analyses. It does not report estimates of comparative effects, confidence intervals, or statistical tests in the information analyzed. Without those results, there is no reported inferential estimate to interpret. General statistical methods can explain what such estimates would mean, but they cannot replace results that are not reported in the registry record.
General statistical principle: when event counts are sparse or group sizes differ, estimates can be unstable and uncertainty can be substantial. A difference in raw counts alone does not account for the size or composition of groups. More formal comparisons would require a defined estimand, an analysis population, a statistical model, and assumptions about missing observations and follow-up. Those details are not reported in the registry record. Accordingly, the most defensible reading is descriptive: the record reports who was affected within each listed cohort, without establishing causation or comparative effects.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Cohort 1 (25 mg) | 2 | 2 | 100.0% | 15.8% to 100.0% | 34.2% to 100.0% | 29.2% to 99.2% |
| Cohort 2 (50 mg) | 3 | 3 | 100.0% | 29.2% to 100.0% | 43.9% to 100.0% | 39.8% to 99.4% |
| Cohort 3 (75 mg) | 3 | 3 | 100.0% | 29.2% to 100.0% | 43.9% to 100.0% | 39.8% to 99.4% |
| Cohort 4 (100 mg) | 6 | 6 | 100.0% | 54.1% to 100.0% | 61.0% to 100.0% | 59.0% to 99.6% |
| Cohort 5 (125 mg) | 55 | 54 | 98.2% | 90.3% to 100.0% | 90.4% to 99.7% | 90.4% to 99.6% |
| Cohort 6 (150 mg) | 4 | 4 | 100.0% | 39.8% to 100.0% | 51.0% to 100.0% | 47.8% to 99.5% |
R code and output
arm <- c("Cohort 1 (25 mg)", "Cohort 2 (50 mg)", "Cohort 3 (75 mg)", "Cohort 4 (100 mg)", "Cohort 5 (125 mg)", "Cohort 6 (150 mg)")
n <- c(2, 3, 3, 6, 55, 4)
events <- c(2, 3, 3, 6, 54, 4)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Cohort 1 (25 mg) 2 2 100.0 15.8 100.0 34.2 100.0 29.2 99.2
ARM Cohort 2 (50 mg) 3 3 100.0 29.2 100.0 43.9 100.0 39.8 99.4
ARM Cohort 3 (75 mg) 3 3 100.0 29.2 100.0 43.9 100.0 39.8 99.4
ARM Cohort 4 (100 mg) 6 6 100.0 54.1 100.0 61.0 100.0 59.0 99.6
ARM Cohort 5 (125 mg) 55 54 98.2 90.3 100.0 90.4 99.7 90.4 99.6
ARM Cohort 6 (150 mg) 4 4 100.0 39.8 100.0 51.0 100.0 47.8 99.511. Multiplicity, Missing Data and Analysis Populations
The registry record lists 15 outcome measures. The secondary outcomes include overall response rate, partial remission rate, duration of response, relapse-free survival, overall survival, event-free survival, transfusion conversion rate, and transfusion maintenance rate. Considering many outcomes can raise a multiplicity issue: when several hypotheses are tested, the chance of at least one apparently notable result can increase. General statistical practice may address this through prespecified testing hierarchies or other adjustments, but the registry record does not report a multiplicity plan.
The record lists zero analyses. It does not report inferential results for the primary or secondary outcomes in the information analyzed. The presence of registered outcomes should not be mistaken for evidence that each was analyzed or that a particular statistical procedure was used. The analysis plan, including any interim analyses, is not reported in the registry record.
Missing-data handling is also not reported in the registry record. The record defines the safety population as participants who received at least 1 dose of MEN1703, but does not describe how incomplete follow-up, unavailable outcome measurements, or withdrawals were handled. The primary endpoint timeframe is up to 21 months; the record does not provide further detail on observation time for each participant.
The safety population is specified for the primary endpoint. Analysis populations for the secondary response and time-to-event outcomes are not reported in the registry record. Without information about exclusions, missing observations, and population definitions, readers cannot determine how those outcomes would be analyzed or how sensitive results might be to missing data.
12. 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 |
|---|---|---|---|
| Cohort 1 (25 mg) | 0 | 2 | 0.0% |
| Cohort 2 (50 mg) | 0 | 3 | 0.0% |
| Cohort 3 (75 mg) | 3 | 3 | 100.0% |
| Cohort 4 (100 mg) | 6 | 6 | 100.0% |
| Cohort 5 (125 mg) | 35 | 55 | 63.6% |
| Cohort 6 (150 mg) | 4 | 4 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cohort 1 (25 mg) | 2 of 2 |
| Cohort 2 (50 mg) | 3 of 3 |
| Cohort 3 (75 mg) | 3 of 3 |
| Cohort 4 (100 mg) | 1 of 6 |
| Cohort 5 (125 mg) | 35 of 55 |
| Cohort 6 (150 mg) | 4 of 4 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cohort 1 (25 mg) | 2 of 2 |
| Cohort 2 (50 mg) | 3 of 3 |
| Cohort 3 (75 mg) | 3 of 3 |
| Cohort 4 (100 mg) | 6 of 6 |
| Cohort 5 (125 mg) | 52 of 55 |
| Cohort 6 (150 mg) | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1 (25 mg) | Cohort 2 (50 mg) | Cohort 3 (75 mg) | Cohort 4 (100 mg) | Cohort 5 (125 mg) | Cohort 6 (150 mg) |
|---|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 0 of 2 | 0 of 3 | 1 of 3 | 0 of 6 | 17 of 55 | 1 of 4 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 2 | 0 of 3 | 2 of 3 | 1 of 6 | 8 of 55 | 1 of 4 |
| Sepsis | Infections and infestations | 0 of 2 | 0 of 3 | 1 of 3 | 0 of 6 | 5 of 55 | 1 of 4 |
| Pneumonia fungal | Infections and infestations | 0 of 2 | 0 of 3 | 0 of 3 | 0 of 6 | 3 of 55 | 0 of 4 |
| Colitis | Gastrointestinal disorders | 0 of 2 | 0 of 3 | 0 of 3 | 0 of 6 | 1 of 55 | 1 of 4 |
| Intestinal haemorrhage | Gastrointestinal disorders | 0 of 2 | 0 of 3 | 0 of 3 | 0 of 6 | 2 of 55 | 0 of 4 |
| Non-cardiac chest pain | General disorders | 0 of 2 | 0 of 3 | 0 of 3 | 1 of 6 | 1 of 55 | 0 of 4 |
| Pyrexia | General disorders | 0 of 2 | 0 of 3 | 0 of 3 | 0 of 6 | 2 of 55 | 0 of 4 |
| Anorectal infection | Infections and infestations | 0 of 2 | 0 of 3 | 0 of 3 | 0 of 6 | 2 of 55 | 0 of 4 |
| Cellulitis | Infections and infestations | 0 of 2 | 0 of 3 | 0 of 3 | 0 of 6 | 2 of 55 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1 (25 mg) | Cohort 2 (50 mg) | Cohort 3 (75 mg) | Cohort 4 (100 mg) | Cohort 5 (125 mg) | Cohort 6 (150 mg) |
|---|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 0 of 2 | 1 of 3 | 1 of 3 | 2 of 6 | 26 of 55 | 2 of 4 |
| Anaemia | Blood and lymphatic system disorders | 0 of 2 | 2 of 3 | 3 of 3 | 3 of 6 | 17 of 55 | 0 of 4 |
| Asthenia | General disorders | 0 of 2 | 0 of 3 | 0 of 3 | 0 of 6 | 19 of 55 | 0 of 4 |
| Aspartate aminotransferase increased | Investigations | 0 of 2 | 0 of 3 | 2 of 3 | 1 of 6 | 13 of 55 | 2 of 4 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 2 | 1 of 3 | 1 of 3 | 0 of 6 | 13 of 55 | 1 of 4 |
| Vomiting | Gastrointestinal disorders | 0 of 2 | 1 of 3 | 0 of 3 | 1 of 6 | 13 of 55 | 1 of 4 |
| Fatigue | General disorders | 0 of 2 | 2 of 3 | 1 of 3 | 3 of 6 | 7 of 55 | 3 of 4 |
| Diarrhoea | Gastrointestinal disorders | 1 of 2 | 2 of 3 | 1 of 3 | 2 of 6 | 7 of 55 | 2 of 4 |
| Alanine aminotransferase increased | Investigations | 0 of 2 | 0 of 3 | 2 of 3 | 1 of 6 | 9 of 55 | 3 of 4 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 2 | 1 of 3 | 1 of 3 | 1 of 6 | 9 of 55 | 2 of 4 |
Serious events with the highest arm-level rate: febrile neutropenia (66.7%), bacteraemia (33.3%), pneumonia (33.3%), sepsis (33.3%), urinary tract infection (33.3%).
The serious adverse event summaries report participants at risk and participants affected within each dose cohort. The affected counts are 0 of 2 for Cohort 1 (25 mg), 0 of 3 for Cohort 2 (50 mg), 3 of 3 for Cohort 3 (75 mg), 6 of 6 for Cohort 4 (100 mg), 35 of 55 for Cohort 5 (125 mg), and 4 of 4 for Cohort 6 (150 mg). The other adverse event summaries report 2 of 2, 3 of 3, 3 of 3, 6 of 6, 52 of 55, and 4 of 4, respectively.
These are descriptive participant counts, not evidence that MEN1703 caused the events. The registry definition includes events regardless of whether they were considered related to the investigational product. The listed deaths are 2, 3, 3, 1, 35, and 4 by cohort, but the record does not provide a causal attribution for those deaths in the information analyzed. The serious-event terms and percentages are registry summaries; without additional denominators and event-level context, they should not be used to compare risks across cohorts.
13. What the Result Does, and Does Not, Mean
The posted results provide a description of adverse events recorded among participants treated with MEN1703 in the listed dose cohorts. They identify the number of participants at risk and affected by serious and other adverse events, and they report deaths by cohort. The serious-event terms include febrile neutropenia, bacteraemia, pneumonia, sepsis, urinary tract infection, and fall. These details contribute to a descriptive safety account.
They do not establish that MEN1703 caused any particular event or death. The adverse event definition explicitly does not require a causal relationship to treatment, and the record describes the safety summaries as regardless of causality. Nor do the counts establish that one dose is safer or less safe than another. The study was non-randomized, had no control group, and the cohorts are not a like-for-like comparison.
The registry’s stated purpose included identifying the maximum tolerated dose and further investigating safety. However, the information analyzed does not report a maximum tolerated dose result or a result for the primary endpoint. It also does not provide inferential analyses, confidence intervals, or adjusted comparisons. The secondary outcomes are listed, but results for them are not reported in the registry record in the information analyzed.
General statistical principle: descriptive counts can show what was recorded in a study, while causal conclusions require a design and analysis that support comparison and address uncertainty. The posted cohort summaries are best read as counts within the groups studied. They do not, on their own, establish comparative effectiveness, safety relative to another treatment, or a dose-response relationship.
14. Why This Trial Matters Statistically
This study illustrates the role of descriptive safety reporting in an early-phase dose evaluation. Its stated purpose was to identify the maximum tolerated dose of MEN1703 and further investigate its safety profile in participants with AML. Reporting participant counts by dose cohort can make the recorded safety experience more transparent, including serious and other adverse events and deaths.
It also illustrates why design matters when interpreting those counts. A non-randomized study without a control group can describe what happened among treated participants, but does not provide the same basis for causal comparison as a randomized controlled design. The dose cohorts are not interchangeable controls, and cohort differences cannot be attributed to dose from these descriptive summaries alone.
The registry record also makes visible an important distinction between registered outcomes and reported analyses. It lists a primary safety endpoint and multiple secondary outcomes, yet lists zero analyses. A planned or registered outcome is not itself a reported estimate. Without results and their uncertainty, readers cannot evaluate the precision of an effect estimate or an inferential claim.
For biostatisticians and clinical researchers, the record is a reminder to interpret safety counts alongside definitions, analysis populations, follow-up, and the design’s capacity for comparison. Here, the safety population is defined, but handling of missing data, the detailed analysis plan, and comparative inferential results are not reported in the registry record. These limitations shape what the posted counts can support: a description of recorded events, rather than a controlled conclusion about treatment effects.
15. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary endpoint result is not reported in the registry record in the information analyzed. Although the registry describes the endpoint and its safety population, it does not give an overall participant count for that endpoint. The record also lists zero analyses, so no inferential estimate or uncertainty interval is available for interpretation.
The study was non-randomized, unmasked, and single-group, with no control intervention. The dose cohorts therefore cannot serve as like-for-like controls. Participant characteristics and follow-up may differ between cohorts, and the record does not report adjusted comparisons or information establishing cohort comparability. The descriptive counts cannot establish causation or a dose-related change in risk.
The record does not report the maximum tolerated dose result, a sample-size justification, detailed dose-transition rules, interim analyses, or the statistical analysis plan. It also does not report the handling of missing data, the analysis populations for secondary outcomes, or event-level context sufficient to interpret the reported deaths and serious-event percentages. The listed secondary outcomes do not have results in the information analyzed.
The registry reports serious and other adverse event counts by cohort and identifies event terms with percentages, but those summaries do not provide a complete account of timing, recurrence, severity gradations, or causal attribution in the information analyzed. These omissions limit interpretation of safety patterns and make direct cohort comparisons particularly uncertain.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: MEN1703 (SEL24) in Participants With Acute Myeloid Leukemia — NCT03008187.
- Registry record last updated 2025-04-29; status last verified 2025-03.
- Results first posted 2025-04-29.
- 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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19. Record Summary
The completed registry record describes a Phase I/II, non-randomized, unmasked, single-group study of MEN1703 in participants with AML. Enrollment is listed as 73. Participants received oral MEN1703 in dose cohorts of 25 mg, 50 mg, 75 mg, 100 mg, 125 mg, or 150 mg, once daily for 14 consecutive days in cycles of 21 days.
The primary endpoint was the number of participants experiencing treatment-emergent adverse events, in a safety population defined as participants who received at least 1 dose, with a timeframe of up to 21 months. The registry lists multiple secondary outcomes and reports serious and other adverse event counts and deaths by cohort. It lists zero analyses. The primary endpoint result, maximum tolerated dose result, inferential comparisons, missing-data methods, and statistical analysis plan are not reported in the registry record in the information analyzed.