Asciminib Treatment Optimization in ≥ 3rd Line CML-CP: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Asciminib Treatment Optimization in ≥ 3rd Line CML-CP (NCT04948333), a na phase 3 study. The primary outcome is Major Molecular Response (MMR) Rate at Week 48 for All Patients With no Evidence of MMR at Baseline.

2. Clinical Question

The study is titled as treatment optimization, so its central focus is the asciminib regimen and response over time in a population previously treated with multiple tyrosine kinase inhibitors. The primary question is narrower than the full study: it concerns week 48 MMR among patients who did not have MMR at baseline. Secondary outcomes include response rates at other listed time points and other molecular or cytogenetic response measures. Those additional outcomes do not change the interpretation of the primary question, and their results are also not reported in the registry record.

3. Trial Design

The registry identifies NCT04948333 as a Phase 3b, multicenter, open-label, treatment-optimization study. The official title specifies oral asciminib in patients with chronic myelogenous leukemia in chronic phase who had previously received 2 or more tyrosine kinase inhibitors. The record lists the study as completed and gives an enrollment of 199.

The design is recorded as single-group, with no masking and allocation listed as not applicable. Asciminib is listed in schedules of 40 mg twice daily and 80 mg once daily. The arm description says patients receive 80 mg in either schedule, with possible escalation to 200 mg once daily under specified response conditions and at the investigator's discretion. Because the escalation description ends mid-sentence, its remaining details are not reported in the registry record.

The record does not describe a randomized comparison. Although two schedules are listed, the registry explicitly cautions that these are not like-for-like control arms. Differences between people receiving the schedules therefore cannot be interpreted as a randomized treatment contrast using the information in this record. The study's single-group designation also means that a concurrent comparator is not described.

The primary completion date is 2024-03-12, and the record status is completed. These are study-status details, not evidence that the primary outcome result has been posted. The record lists 21 outcome measures and 0 analyses. Eligibility criteria beyond the disease setting and prior treatment history, details of treatment exposure, and reasons for any treatment changes are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS)

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.

6. Primary Endpoint

The registry lists the primary outcome as Major Molecular Response (MMR) Rate at Week 48 for All Patients With no Evidence of MMR at Baseline, measured over Week 48.

The primary endpoint is the MMR rate at week 48 among patients with no evidence of MMR at baseline. It is expressed as the percentage of responders, with a 95% confidence interval specified as the dispersion measure. The named analysis population is the Full Analysis Set. The registry record does not report the observed percentage or its confidence interval.

The registry defines MMR as a significant reduction in BCR::ABL1 transcripts, the genetic markers described for chronic myeloid leukemia. Specifically, it requires a reduction of at least 3.0 log compared with a standardized baseline, corresponding to a BCR::ABL1/ABL1 ratio of at most 0.1% on the international scale. The endpoint therefore classifies whether the molecular-response threshold has been reached by the specified assessment time.

In general, a response-rate endpoint is useful because it gives a direct summary of the proportion meeting a prespecified response definition at a particular time point. The confidence interval indicates the precision of that estimate: a narrower interval means greater precision, while a wider interval indicates greater uncertainty about the underlying response rate. Without the estimate and interval, the registry record does not allow readers to assess either the response frequency or its precision.

MMR is a molecular measure. It should not be treated as equivalent to every other clinical outcome, such as symptoms, quality of life, or survival. The registry lists those types of outcomes only insofar as they are specified; no such results are reported in the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a binary response-rate endpoint and a confidence interval, but does not report the analysis results or the statistical methods in enough detail to reconstruct the endpoint analysis. The explanations below distinguish the general statistical concepts from the specific information recorded for this study.

What does a response rate estimate?

In general, a response rate is the proportion of an analysis population that meets a defined response criterion. For this endpoint, response means reaching MMR at week 48 among patients with no evidence of MMR at baseline. A response-rate estimate depends on both the response definition and the population included in the calculation. The registry names the Full Analysis Set but does not report its detailed membership, the number assessed at week 48, or the number classified as responders.

The endpoint is binary at the participant level: a person either meets the stated MMR definition at the assessment or does not. That does not mean the underlying biological measurement is itself only binary; rather, the endpoint applies a threshold to that measurement to classify response. The registry defines the threshold using the BCR::ABL1/ABL1 ratio and the reduction from standardized baseline.

What does the confidence interval communicate?

In general, a confidence interval describes the precision of an estimate under a specified statistical method. It is read alongside the estimated response rate, not as a replacement for it. A narrower interval indicates less sampling uncertainty around the estimate, while a wider interval indicates greater uncertainty. The record specifies a 95% confidence interval for the primary response rate, but does not give the estimated rate, interval limits, or the method used to calculate the interval. The interval therefore cannot be evaluated from the registry record.

A confidence interval does not account automatically for every source of uncertainty. It does not by itself resolve concerns about missing assessments, how the analysis population was defined, the representativeness of the study participants, or the lack of a randomized comparator. Those issues require separate design and analysis information, much of which is not reported in the registry record.

Why does the single-group design affect interpretation?

In general, random assignment helps make treatment groups comparable with respect to both measured and unmeasured characteristics. This registry lists a single-group model and no allocation procedure. Its two listed schedules are not designated as randomized control arms, and the record explicitly warns against treating them as a like-for-like control comparison. Any descriptive differences between schedule groups could reflect how patients entered or moved through treatment, baseline differences, or other factors, as well as the schedule itself.

The possible escalation to 200 mg once daily is part of the recorded treatment strategy for specified response circumstances. It means exposure may depend on response history and investigator judgment. The registry description does not give enough detail to characterize how escalation was implemented across participants. In general, when treatment changes depend on a patient's earlier outcome, a simple comparison of later outcomes by dose may be affected by that selection process.

How should the endpoint time point be understood?

The primary measure is tied to week 48, so it concerns response status at that assessment time rather than response at any time during follow-up. The listed secondary measures cover other time points and response definitions. In general, repeated assessments can describe the timing and course of response, but separate rates at different time points do not necessarily represent independent findings. The registry lists a time-to-MMR outcome as well, but does not report its results or its analysis method.

For a time-to-event outcome, general analysis methods account for when an event occurs and may address incomplete follow-up through censoring assumptions. These methods differ from a response-rate analysis at a fixed assessment. The registry record does not report the time-to-MMR estimates, event definitions beyond the listed outcome title, censoring rules, or statistical method.

What can be inferred from the listed analysis information?

The registry names the Full Analysis Set for the primary endpoint and lists 21 outcome measures, but it records 0 analyses. The outcome measure list identifies questions the study intended to assess; it does not supply observed findings. No response percentage, confidence interval, hypothesis test, model estimate, or adjusted analysis result for the primary endpoint is reported in the registry record.

In general, an unadjusted response rate is a direct summary of observed outcomes, while an adjusted analysis accounts for selected covariates using a specified model. The registry record does not report whether the primary endpoint was adjusted, how any covariates were selected, or whether sensitivity analyses were conducted. These details are not reported in the registry record and should not be inferred from the endpoint description alone.

In general, over-dispersion refers to variability greater than a statistical model expects under its assumptions. It can matter for count or rate data when the model's variance assumptions are too restrictive. This primary endpoint is a binary percentage rather than a count rate, and the registry record does not report a model-based analysis or any over-dispersion assessment. This concept therefore does not establish a method used in this study.

The registry describes the endpoint's confidence interval but does not identify the specific interval construction, missing-data approach, or statistical analysis plan. Those methods affect how an estimate should be interpreted, so their absence limits independent assessment. General explanations of response rates and confidence intervals cannot substitute for the study's unreported analysis details.

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("Asciminib 40 mg b.i.d. - Subjects Without MMR at B", "Asciminib 80 mg q.d. - Subjects Without MMR at Bas")
n      <- c(85, 84)
events <- c(36, 29)
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  Asciminib 40 mg b.i.d. - Subjects Without MMR at B  85  36  42.4  31.7  53.6  32.4  53.0  32.4  53.0
ARM  Asciminib 80 mg q.d. - Subjects Without MMR at Bas  84  29  34.5  24.5  45.7  25.2  45.2  25.2  45.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 21 outcome measures, including the primary week 48 MMR rate and several secondary response measures at other time points or in different baseline groups. It records 0 analyses, and does not report outcome estimates or statistical tests. The registry record does not report a multiplicity procedure, such as a method to control the chance of false-positive findings across multiple outcome tests, nor does it state whether any outcomes were considered exploratory. Without that information and the results, the listed outcomes cannot be treated as a set of confirmed statistical findings.

The primary endpoint is defined for patients with no evidence of MMR at baseline, while a listed secondary endpoint concerns patients with MMR at baseline. The distinction is important: the groups begin in different response states, and their response rates answer different questions. Other listed outcomes use different response thresholds or assessment times. Comparing such measures without their definitions, analysis populations, and results could be misleading.

The Full Analysis Set is named for the primary endpoint, but its operational definition is not reported in the registry record. The record also does not report the number contributing to the analysis, the number with missing week 48 measurements, or how missing response status was treated. In general, missing-data rules can affect a response-rate estimate, especially if the likelihood of an unobserved assessment is related to a participant's health or response. No particular missing-data assumption or method can be attributed to this study from the registry information.

The registry record does not report an interim analysis plan, sample-size justification, or detailed statistical analysis plan. Its absence should not be filled in by assuming common practice. The listed enrollment and endpoint description do not establish how precision or statistical decision-making was planned.

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: coronary artery disease (7.1%), blindness unilateral (7.1%), incisional hernia (7.1%), lipase increased (7.1%), angina pectoris (6.2%).

The registry lists adverse-event figures separately for patients without MMR at baseline and patients with MMR at baseline, with entries for asciminib 40 mg twice daily and 80 mg once daily. For the groups without MMR at baseline, the serious-event figures are 9 among 84 at risk for each listed schedule. For the groups with MMR at baseline, the figures are 4 among 14 for 40 mg twice daily and 5 among 16 for 80 mg once daily. These are the group-level figures recorded; they should not be combined into a new overall estimate.

The record also lists other adverse-event figures of 67 among 84 for each schedule in the no-MMR-at-baseline groups, 12 among 14 for the 40 mg twice-daily group with MMR at baseline, and 15 among 16 for the 80 mg once-daily group with MMR at baseline. The death entries are 0, 1, 0, and 0 in the order of the four listed groups. These counts do not by themselves describe event severity beyond the categories stated in the registry.

Listed serious-event terms include coronary artery disease, blindness unilateral, incisional hernia, and lipase increased at 7.1% each, and angina pectoris and pancreatitis acute at 6.2% each. The registry does not report the denominators or additional detail needed to compare these term percentages across groups. Event terms may not represent mutually exclusive participants, and the listed percentages should not be interpreted as a comparative risk estimate. The study has no randomized control group, and the record does not provide a causal safety comparison.

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

The registry record establishes the study's treatment setting, design, and intended primary endpoint. It asks about the week 48 MMR rate among patients without MMR at baseline who were treated with asciminib under a treatment-optimization strategy. The molecular definition of MMR is specified, and the Full Analysis Set is named. These details clarify what the primary endpoint was intended to measure.

The record does not report the primary endpoint estimate or its confidence interval. It therefore does not show the observed response rate or the precision of that rate. The same limitation applies to the secondary outcomes: their titles are listed, but their results are not reported in the registry record. Statistical or clinical conclusions about those outcomes cannot be drawn from their presence in the outcome list.

In general, an observed response rate describes the frequency of a defined outcome in the analyzed group. Even if that rate and its confidence interval were available, a single-group study would not by itself establish what would have happened to a comparable population under another treatment strategy. This registry describes no randomized control group and cautions that the listed schedule groups are not like-for-like comparisons. The record therefore does not support attributing differences to a dose schedule or making a controlled treatment-effect comparison.

The endpoint is molecular and time-specific. It does not, by itself, establish outcomes that were not measured by this endpoint, such as symptoms, quality of life, or survival. Likewise, an event count in the safety listing is not a complete account of an individual patient's experience or proof of a comparative safety effect. The registry record gives selected adverse-event summaries, but those summaries do not replace a controlled safety analysis.

In short, the record can be used to understand what investigators planned to assess and how the study was structured. It cannot be used to state whether the primary response threshold was commonly reached, how certain an estimated rate would be, or whether asciminib performed better or worse than another treatment. The outcome findings needed for those conclusions are not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises several important statistical questions that are not answered by a response percentage alone. The population is defined by prior treatment and baseline molecular-response status, and the primary endpoint focuses on patients without MMR at baseline. Specifying the baseline group helps make clear which clinical question a response rate addresses. It also prevents inappropriate comparisons with outcomes in patients who began in a different response state.

The treatment-optimization feature is statistically relevant because the recorded strategy allows possible dose escalation based on response and investigator judgment. In general, treatment changes that depend on earlier outcomes can make later comparisons between dose groups difficult to interpret. A randomized design and a prespecified analysis can address some comparison questions, but the registry describes a single-group study and does not report a detailed analysis plan.

The outcome definition is also explicit: MMR is based on a molecular threshold and is assessed at week 48 for the primary endpoint. A well-defined threshold and time point support consistent interpretation of a response-rate estimate. The specified 95% confidence interval would communicate the estimate's precision, but the registry record does not report the estimate or interval.

The record's limitations are as important as its design details. It lists 21 outcomes and 0 analyses, while the primary and secondary results are not reported. Without those results, readers cannot examine the response frequency, uncertainty, or patterns across the other listed outcomes. The lack of a randomized comparator also limits causal interpretation, independent of how clearly the molecular endpoint is defined.

Statistically, the record is a useful example of why a study's question, population, endpoint, and design must be read together. The endpoint identifies a specific response target; the single-group design constrains comparison; and the absence of outcome results prevents assessment of the observed data. These distinctions help separate what the registry documents from what would require posted analysis results.

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 registry record does not report the primary week 48 MMR rate or its 95% confidence interval. It also does not report results for the listed secondary outcomes, despite listing 21 outcome measures. This is the central limitation for interpreting efficacy-related findings: the outcomes are defined, but the observed estimates and their precision are absent.

The study is recorded as single-group, with allocation not applicable and no masking. There is no randomized control group, and the registry specifically cautions that the schedule groups are not a like-for-like comparison. As a result, descriptive differences between those groups cannot be treated as randomized treatment effects. The possible response-dependent dose escalation further means that the treatment strategy can change with a participant's response history and investigator judgment.

The record lists enrollment of 199 and names the Full Analysis Set for the primary endpoint, but does not report the analysis denominator, the detailed population definition, or how missing week 48 assessments were handled. It does not describe the statistical method for calculating the confidence interval, any adjustment for covariates, or sensitivity analyses. Multiplicity handling, interim analyses, and the statistical analysis plan are not reported in the registry record.

The dose-escalation description is incomplete, ending after the investigator's opinion that the patient may benefit from escalation. The remaining conditions and implementation details are not reported in the registry record. Eligibility criteria beyond the stated disease context and prior treatment history, treatment exposure details, and participant flow are also not reported.

The safety entries provide group counts and selected serious-event terms, but the record does not give enough information to make controlled comparisons or fully assess how events were defined and collected. The listed percentages for individual event terms lack contextual detail in the record. These limitations restrict interpretation of both efficacy and safety summaries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Asciminib Treatment Optimization in ≥ 3rd Line CML-CP — NCT04948333.
• Registry record last updated 2026-03-18; status last verified 2026-03.
• Results first posted 2025-03-27.
• 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

NCT04948333 is a completed Phase 3b, multicenter, open-label, single-group study of oral asciminib in chronic-phase CML after treatment with 2 or more tyrosine kinase inhibitors. The record lists enrollment of 199 and describes 40 mg twice-daily and 80 mg once-daily schedules, with possible escalation to 200 mg once daily under specified response circumstances.

The primary endpoint is the week 48 MMR rate among patients without evidence of MMR at baseline, using the Full Analysis Set and a specified 95% confidence interval. The MMR definition uses a reduction of at least 3.0 log in BCR::ABL1 transcripts, corresponding to a BCR::ABL1/ABL1 ratio of at most 0.1% on the international scale.

The registry lists 21 outcome measures and 0 analyses. The primary estimate, its confidence interval, and secondary outcome results are not reported in the registry record. The design does not include a randomized control group, and the record cautions against treating the listed schedule groups as like-for-like comparisons.