First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) (NCT05086315), a na phase 1, phase 2 study. The primary outcome is Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

NCT05086315 is described as an open-label, multicenter, first-in-human Phase 1/Phase 2 study of SAR443579 as a single agent. The study has a dose-escalation phase and a dose-expansion phase. Its listed allocation is not applicable, masking is none, and the model is single-group. Consequently, there is no randomized control arm for comparison.

The study enrolled 101 participants. Its listed conditions include acute lymphocytic leukemia, refractory acute myeloid leukemia, myelodysplastic syndromes, and blastic plasmacytoid dendritic cell neoplasia. The title and study description specify adult and pediatric participants with relapsed or refractory acute myeloid leukemia, B-cell acute lymphoblastic leukemia, high-risk myelodysplasia, or blastic plasmacytoid dendritic cell neoplasm.

During dose escalation, SAR443579 was given intravenously at escalating dose levels. During dose expansion, it was given at the recommended dose and schedule determined through escalation. The primary endpoint applies to dose escalation and counts participants with DLTs during the first treatment cycle. Secondary outcomes include selection of a recommended dose for expansion, adverse events, drug concentration and anti-drug antibodies, and response measures in specified cohorts.

The registry lists a start date of 2021-12-08, a primary completion date of 2025-06-13, and a status of terminated. The reason for termination and the resulting effect on planned enrollment or follow-up are not reported in the registry record. The record does not report a separate control group or randomized treatment assignment.

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: Study included adult (\>=18 years) and pediatric (1 to \<18 years; \>=2 years in France) arms with dose escalation and dose expansion/optimization phases. Study was terminated after completion of dose escalation phase of adult and pediatric arms and dose expansion/optimization phase of adult arm (Cohort A1), for non-safety related reasons. Dose expansion/optimization part of adult (Cohorts A2, B and C) and pediatric arms (Cohort D) were not initiated. Only results from completed parts are reported.

Only the first 6 of 15 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All treated population included all participants who had given their informed consent and received at least any dose (even incomplete) of study treatment.

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: All treated population included all participants who had given their informed consent and received at least any dose (even incomplete) of study treatment.

Only the first 6 of 16 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs), measured over Cycle 1 Day 1 up to Cycle 1 Day 28. Each cycle duration in induction period was 28 days..

The primary endpoint is the number of participants with dose-limiting toxicities during dose escalation. The observation window is Cycle 1 Day 1 up to Cycle 1 Day 28; each induction-period cycle lasted 28 days. A DLT is a defined safety event within that early treatment window, rather than a measure of disease response or long-term outcome.

The registry specifies hematologic and non-hematologic criteria. Hematologic criteria include specified severe blood-count toxicities and bone marrow hypocellularity. Non-hematologic criteria include defined higher-grade toxicities, with listed exceptions, as well as certain tumor lysis, infusion-related, laboratory, and treatment-delay or dose-reduction events. The definition uses NCI CTCAE v5.0 or ASTCT criteria and includes events whether or not they were attributed to study treatment, subject to the stated exceptions for disease progression or clear contrary evidence.

In general, an early-cycle DLT endpoint is used in dose escalation to characterize tolerability at candidate dose levels and inform dose selection. It focuses attention on predefined events in a common early window. The registry also lists a recommended dose for expansion as a secondary outcome. The actual number of DLTs and the selected dose are not reported in the registry record, so the endpoint definition alone does not show what was observed or how dose selection proceeded.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is labeled Phase 1/Phase 2 and combines dose escalation with dose expansion. In general, dose escalation examines successive dose levels to inform further study, while dose expansion evaluates a selected dose in additional participants or cohorts. This design differs from a randomized trial intended to compare treatment with a concurrent control. Here, the registry identifies a single-group model and no masking.

What does the primary endpoint count?

The primary outcome is a participant count: the number of participants with at least one event meeting the registry’s DLT definition during the specified Cycle 1 window. This is a binary outcome at the participant level—each person either meets the DLT definition or does not—summarized as a count. The registry defines the analysis population as all treated participants, including those receiving any dose, even an incomplete dose. It does not report the observed count or the corresponding analysis result.

The DLT definition is operational: it lists which events qualify and the time window in which they must occur. That detail matters because a safety count depends on the event criteria and observation period. The definition includes hematologic and non-hematologic events, with specified exceptions and rules relating to treatment delays or dose reductions. The registry does not report further details about adjudication or how any borderline cases were classified.

How should dose groups be understood?

In general, outcomes across dose groups can describe the experience at different dose levels, but a nonrandomized dose-escalation sequence is not a controlled comparison. Participants at different levels may differ, and dose assignment may be linked to the escalation process. The listed adult and pediatric dose groups and the adult expansion cohort should therefore be read as study cohorts, not as interchangeable groups that provide a treatment-effect contrast.

The registry’s safety entries report numbers at risk and numbers affected for serious and other adverse events, as well as deaths, for listed groups. A count is not the same as a risk estimate unless its denominator and event definition are considered. In general, percentages or rates are easier to compare than raw counts when group sizes differ, but even rates from small, nonrandomized cohorts can be imprecise and confounded. No additional comparative safety analysis is reported in the registry record.

What do confidence intervals and tests contribute?

General statistical explanation: a confidence interval expresses the uncertainty around an estimate under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, while neither an interval nor a p-value resolves biases created by study design or incomplete data. The registry record does not report a confidence interval, hypothesis test, or p-value for the primary DLT endpoint. It also lists zero analyses, so the posted record does not give a statistical analysis result to interpret.

General statistical explanation: statistical tests are most useful when the question, comparison, endpoint, and analysis population are specified in advance. Without a randomized control group, a test of differences between dose cohorts would not, by itself, turn those differences into a causal treatment comparison. The registry record does not report a statistical analysis plan, a prespecified primary contrast, or details of any adjustment for covariates.

What do the planning assumptions mean?

The registry-associated planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of an observed effect. For time-to-event outcomes, the stated planning approach counts total events; for other outcomes, it reports participants per arm. These are planning assumptions, not evidence that the trial used a two-arm design. The actual study is listed as single-group, and the registry record does not report the trial’s own sample-size justification or observed-effect estimates on which such illustrations could be based.

General statistical explanation: a sample-size calculation describes a design scenario under selected assumptions. It is not an observed result and is not observed power. In particular, an illustration based on an observed effect should not be read as a prospective justification for this study or as proof that its outcomes were adequately powered. The record does not report the protocol’s sample-size rationale, interim analyses, or a complete statistical analysis plan.

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.

R code and output

arm    <- c("Dose Escalation - Adult Arm: SAR443579 10-100 mcg/", "Dose Escalation - Adult Arm: SAR443579 30-300 mcg/", "Dose Escalation - Adult Arm: SAR443579 750 mcg/kg", "Dose Escalation - Adult Arm: SAR443579 800 mcg/kg", "Dose Escalation - Adult Arm: SAR443579 100-1000 mc", "Dose Escalation - Adult Arm: SAR443579 300-1000 mc")
n      <- c(3, 4, 6, 10, 4, 4)
events <- c(0, 0, 1, 0, 0, 0)
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  Dose Escalation - Adult Arm: SAR443579 10-100 mcg/  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Dose Escalation - Adult Arm: SAR443579 30-300 mcg/  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Dose Escalation - Adult Arm: SAR443579 750 mcg/kg  6  1  16.7  0.4  64.1  3.0  56.4  3.7  57.9
ARM  Dose Escalation - Adult Arm: SAR443579 800 mcg/kg  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5
ARM  Dose Escalation - Adult Arm: SAR443579 100-1000 mc  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Dose Escalation - Adult Arm: SAR443579 300-1000 mc  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures, spanning safety, drug exposure, immune response, dose selection, and disease response. Several outcomes are attached to particular cohorts, including response measures for Cohort C and overall response measures for specified expansion cohorts. The record does not report a multiplicity strategy, such as a hierarchy of confirmatory tests or adjustment for testing several outcomes. Without that information, any collection of outcome results would need to be interpreted in light of the number and roles of the measures; numerical results are not reported in the registry record.

Missing-data handling is not reported in the registry record. The record does not describe how participants with incomplete follow-up, missed assessments, early discontinuation, or unevaluable response would be treated in each outcome analysis. The primary population is described as all treated participants, but the registry does not state how missing DLT observations within the Cycle 1 window were handled.

Analysis populations beyond the definition for the primary endpoint are not reported in the registry record. The record does not specify, for each secondary outcome, whether the analysis included all treated participants, a cohort-specific subset, or another defined group. It also does not report sensitivity analyses or methods for handling competing events or varying follow-up.

General statistical explanation: multiple outcomes and incomplete observations can affect how confidently results are interpreted. A prespecified testing strategy can distinguish primary questions from exploratory ones, while transparent accounting of missing observations clarifies who contributed to each estimate. These details are especially useful when a study has multiple cohorts and several kinds of outcomes. Their absence from the registry record limits assessment of the analysis, but does not establish that no such procedures existed outside the record.

12. 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 (37.5%), pneumonia (33.3%), sepsis (33.3%), respiratory failure (33.3%), haemorrhoids (33.3%).

The registry reports safety counts separately for listed dose groups. For each group, it gives the number at risk and the number affected by serious adverse events, the number at risk and the number affected by other adverse events, and the number of deaths. These are group-specific counts; they should not be combined across groups without a stated analysis and should not be compared as if participants had been randomized to equivalent arms.

The registry lists Febrile Neutropenia at 37.5% among the most frequent serious adverse event terms. Pneumonia, Sepsis, Respiratory Failure, Haemorrhoids, and Pyrexia are each listed at 33.3%. These are the reported percentages attached to the listed terms. The record does not state in this summary how those percentages were calculated, so they should be read as registry-reported figures rather than recalculated or treated as a direct comparison between dose groups.

General statistical explanation: a serious adverse event is a classification of seriousness, not a statement that the study drug caused the event. Participants with relapsed or refractory hematologic malignancies may experience serious illness-related events, and a single-group study cannot separate those background events from treatment effects as a randomized comparison might. The registry counts therefore describe reported safety experience; attribution and comparative risk are not established by the counts alone.

The registry also reports deaths by dose group, but the cause, timing, and relationship to treatment for each death are not detailed in the registry record of the record. Those counts should not be interpreted as treatment-caused deaths. The reason for study termination is not reported in the registry record.

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

The record establishes that SAR443579 was studied as an intravenous single agent in an open-label, first-in-human Phase 1/Phase 2 dose-escalation and dose-expansion study involving adults and children with selected relapsed or refractory hematologic malignancies. It also identifies the primary safety question: the number of dose-escalation participants with DLTs during Cycle 1 Day 1 up to Cycle 1 Day 28, using a detailed event definition.

The record does not report the primary endpoint result, response estimates, confidence intervals, or inferential tests. It therefore does not allow a reader to determine from the posted results how many participants experienced DLTs, how precisely any outcome was estimated, or what anti-leukemic activity was observed. The presence of response outcomes in the registry is not itself evidence of a response result.

The study’s design also limits what comparisons can be made. There is no randomized control group, and participants in different dose cohorts are not a like-for-like comparison. Observed differences between cohorts, if reported elsewhere, could reflect dose, participant mix, disease characteristics, or other factors. The safety counts do not establish causation, and raw event counts across groups are not a controlled comparison.

The terminated status records the study’s status, but the reason is not reported in the registry record. It cannot support a conclusion about the treatment or the study findings. Similarly, the enrollment figure does not show how many participants were evaluable for each endpoint or whether all planned analyses were completed.

General statistical explanation: conclusions depend on the endpoint definition, the population analyzed, completeness of follow-up, and uncertainty around estimates. Here, the definitions and broad design are available, while primary outcome results and several analysis details are not reported in the registry record. The appropriate reading is therefore descriptive and limited: the record documents what the study was designed to assess and includes group-level safety reporting, but it does not provide enough primary outcome evidence to quantify efficacy or the precision of the DLT result.

14. Why This Trial Matters Statistically

First-in-human dose-escalation studies address questions that differ from the questions answered by a controlled efficacy trial. They characterize early safety and support dose selection, with dose expansion allowing further study at a selected dose. The primary endpoint in this study focuses on predefined toxicities during the first treatment cycle, a time-limited measure intended to inform the escalation stage.

Statistically, the design makes it important to distinguish descriptions of each cohort from estimates of comparative treatment effects. The study is single-group and open-label, with no randomized control. Its dose levels and cohorts can provide context about the observed experience within the study, but they do not create a control comparison. This distinction matters when interpreting both safety counts and any response measures.

The breadth of the registry outcomes is also relevant. The record lists 22 outcomes, including safety, pharmacokinetic and pharmacodynamic measures, anti-drug antibodies, dose selection, and response measures in particular cohorts. A reader needs outcome-specific results, denominators, analysis populations, and uncertainty to understand how much information each measure provides. Those primary and secondary results are not reported in the registry record.

General statistical explanation: early-phase studies often generate estimates that are uncertain, especially when results are reported for distinct cohorts rather than a single large randomized comparison. Transparent reporting of event definitions, follow-up, missing observations, and precision helps distinguish an informative safety signal from a definitive comparative conclusion. The registry offers detailed DLT criteria and some group-level safety counts, but does not provide the primary endpoint result or many analysis details needed for a fuller statistical assessment.

The listed termination status adds context to the study’s record, while the reason for termination is not reported. Statistically, this reinforces the value of interpreting enrollment, completion, and outcome availability separately: the enrolled total alone does not establish that every planned analysis was completed or that every participant contributed to each endpoint.

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 principal limitation for interpreting outcomes is that the primary DLT result is not reported in the registry record. Numerical results for the listed response outcomes and other secondary measures are also not reported. Without estimates and their uncertainty, the registry record cannot establish the observed DLT frequency or quantify the magnitude and precision of disease-response outcomes.

The study has no randomized control group. Its dose levels and cohorts are not a like-for-like comparison, and the open-label design does not conceal treatment assignment. These design features restrict causal interpretation and make direct comparisons between groups vulnerable to differences in participants, disease characteristics, dose, and follow-up. No control-arm effect estimate is available in the record.

Enrollment was 101, but the record does not report how many participants contributed to each outcome analysis, whether all planned cohorts were completed, or how participants with incomplete observations were handled. The registry describes the all-treated population for the primary endpoint, but missing-data procedures and other analysis-population definitions are not reported. The reason for termination is also not reported in the registry record.

The record lists 22 outcome measures and does not report a multiplicity strategy, a statistical analysis plan, or the protocol’s sample-size justification. It does not report interim analyses or confidence intervals for the primary endpoint. As a result, the prespecification and precision of any outcome analyses cannot be assessed from this record alone.

Finally, serious adverse event and death counts are reported by dose group, but the registry record does not establish causation for individual events. The cohort structure and differing group sizes limit direct interpretation of counts as comparative risks. These limitations concern what can be concluded from the registry record; they do not determine what additional information may exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: First-in-human Study of SAR443579 Infusion in Male and Female Children and Adult Participants With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML), B-cell Acute Lymphoblastic Leukemia (B-ALL), High Risk-myelodysplasia (HR-MDS), or Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) — NCT05086315.
• Registry record last updated 2026-07-06; status last verified 2026-06.
• Results first posted 2026-07-06.
• 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.

19. Record Summary

NCT05086315 is a terminated, open-label, multicenter, first-in-human Phase 1/Phase 2 single-group study of intravenous SAR443579. It enrolled 101 adults and children with selected relapsed or refractory hematologic malignancies and included dose escalation followed by dose expansion. The primary endpoint counted participants with DLTs during Cycle 1 Day 1 up to Cycle 1 Day 28.

The registry defines the DLT criteria and lists 22 outcome measures, including safety, drug exposure, anti-drug antibodies, dose selection, and disease-response outcomes. It reports group-level safety counts and several serious adverse event terms with percentages. The primary DLT result and numerical results for the listed response outcomes are not reported in the registry record. The reason for termination, missing-data procedures, multiplicity strategy, and statistical analysis plan are also not reported.