Study of Sonrotoclax (BGB-11417) Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Sonrotoclax (BGB-11417) Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma (NCT05471843), a non-randomized phase 1, phase 2 study. The primary outcome is Part 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs).

2. Clinical Question

The study has two stated aims. Part 1 assesses safety and tolerability and is intended to determine a maximum tolerated dose and a recommended Phase 2 dose. Part 2 evaluates efficacy at the recommended Phase 2 dose with a recommended ramp-up schedule. The listed primary endpoint is a count of participants with dose-limiting toxicities in Part 1, not an efficacy endpoint. The listed secondary outcomes include pharmacokinetic measures and an overall response rate assessed by an independent review committee.

The registry record does not report the observed Part 1 dose-limiting toxicity count or an overall response result. Consequently, the clinical question can be described from the planned outcomes, but the posted information does not establish what the study observed for its primary endpoint or efficacy outcomes.

3. Trial Design

This is a Phase 1/2, single-arm, open-label, multicenter study of sonrotoclax monotherapy in participants with relapsed or refractory mantle cell lymphoma. Allocation is non-randomized, and masking is absent. The registry lists enrollment of 125 and a parallel model, but the listed groups do not create a randomized comparison: they differ by study part, target dose, or ramp-up schedule.

Part 1 investigates safety and tolerability and is intended to identify the maximum tolerated dose and recommended Phase 2 dose. Its listed groups received target doses of 160 mg or 320 mg once daily after a daily ramp-up starting at 1 mg, with dose increases until the target was reached. The descriptions state an approximately 4-week ramp-up. Part 2 evaluates efficacy at the recommended Phase 2 dose and includes listed groups receiving 320 mg once daily, with either daily or twice-weekly ramp-up. The record does not state that participants were randomly assigned among these groups.

Sonrotoclax was continued until disease progression, unacceptable toxicity, or a consent-related stopping condition in the descriptions that are complete enough to specify this. Some group descriptions end mid-sentence, so their full stopping language is not reported in the registry record. Secondary outcomes include measures of drug exposure and concentration, as well as overall response rate assessed by an independent review committee.

The study started on 2022-09-05, has a primary completion date of 2025-07-18, and is listed as active, not recruiting. Those dates and status describe the registry record; they do not establish that all follow-up or analyses are complete. The protocol’s sample-size justification, detailed statistical analysis plan, and any interim-analysis plan 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.

Before assignment: The study was conducted in 2 parts. Part 1 was conducted to determine the recommended sonrotoclax dose in adults with relapsed/refractory mantle cell lymphoma (R/R MCL). Part 2 was designed to assess the efficacy of sonrotoclax in treating adults with R/R MCL.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The DLT-evaluable Set consists of four participants in each group who received \>= 80% of the intended dose over the ramp-up period and \>= 80% of the intended dose over the target dose period of the applicable DLT window and had sufficient safety evaluation or who had a DLT event during the applicable DLT observation window.

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 Part 1: Number of Participants Experiencing Dose-limiting Toxicities (DLTs), measured over From first dose in the ramp-up period through the first 3 weeks of treatment at the target dose (approximately 7 weeks).

The primary endpoint is the number of Part 1 participants experiencing dose-limiting toxicities, or DLTs. It is a count of participants with at least one qualifying toxicity during the specified evaluation window, rather than a count of every toxicity event. That distinction matters because a participant could experience multiple events while contributing once to a participant-count endpoint.

The window runs from the first dose in the ramp-up period through the first 3 weeks of treatment at the target dose, approximately 7 weeks. DLT criteria cover specified hematologic toxicities and nonhematologic toxicities without a clear alternative cause other than study drug. The definition includes exceptions for some events that resolve within stated time limits or after therapeutic intervention. The record describes the DLT-evaluable set as four participants in each group who met dose-exposure and safety-evaluation criteria, or who experienced a DLT during the applicable window; the full population description is truncated.

In general, a DLT endpoint is used in dose-finding work because it focuses attention on toxicities within a defined early treatment window when considering dose and schedule. It is not a complete account of all safety outcomes or longer-term tolerability. The observed DLT count and the detailed analysis result are not reported in the registry record, so the endpoint’s value cannot be interpreted from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what this study can describe from what it can compare. The design is non-randomized and open-label. In general, random allocation helps balance measured and unmeasured characteristics between comparison groups, while masking can reduce some forms of influence on care or assessment. Neither feature is present. The registry explicitly cautions that the groups are not a like-for-like control comparison. Differences among group counts should therefore be treated as descriptive, not as estimates of a treatment effect between interchangeable groups.

What does a participant count represent?

The primary endpoint is a binary outcome at the participant level: each DLT-evaluable participant either meets the DLT definition during the specified window or does not. The reported measure is the count of participants with an event. In general, such a count is easiest to interpret alongside the number of participants evaluated and a clear definition of the analysis population. The registry describes the DLT-evaluable population using dose-exposure and safety-evaluation criteria, with participants who experienced a DLT also included under the stated rule. Its description is truncated, and the primary endpoint result is not reported in the registry record.

A count alone does not indicate precision. In general, uncertainty intervals around a proportion or count-based estimate convey how much the estimate could vary because of the limited amount of observed information. They do not account automatically for selection differences, incomplete follow-up, or other biases. No DLT estimate or interval is reported in the registry record, so there is no posted primary-endpoint precision estimate to interpret.

Why define an evaluation window?

The DLT window begins with the first dose in ramp-up and continues through the first 3 weeks at the target dose, approximately 7 weeks overall. A fixed window makes explicit which treatment period contributes to the endpoint. In general, this supports consistent endpoint classification, but it also means that toxicities outside the window do not count toward this particular endpoint even if they remain relevant to broader safety assessment. The DLT definition further distinguishes qualifying events from specified exceptions, including events resolving within stated limits. The exact rules matter: changing how exceptions are applied can change who is classified as having a DLT.

How should the safety counts be read?

The serious and other adverse-event counts are shown by group. In general, a group-level count describes how many participants had an event under the registry’s reporting definitions; it does not tell whether events were related to treatment unless that attribution is reported. The death counts likewise should not be interpreted as treatment-caused deaths. The record does not give a comparative causal analysis. Follow-up duration and exposure by group are not reported in the registry record, which limits interpretation of differences in cumulative counts. A group with more participants or more observation time may have more recorded events without having a higher underlying event rate.

Over-dispersion is a general issue when analyzing count outcomes: observed counts can vary more than a simple model assumes, for example when event experience differs substantially across participants. It matters because a model that understates variability can produce uncertainty estimates that are too narrow. This trial’s primary endpoint is a participant count for a defined DLT outcome, not a recurrent-event count, and no model or dispersion estimate for its analysis is reported in the registry record. It would be inappropriate to assume a particular count model or variance structure.

What do the planning assumptions describe?

The record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such an illustration is a hypothetical planning exercise, not observed power and not proof that the trial was designed using those assumptions. The arms in this trial are non-randomized and are not a like-for-like control comparison, so the stated equal-allocation setup should not be mistaken for the actual study design. The protocol’s own sample-size justification is not reported in the registry record.

In general, a significance level sets a threshold for a specified testing procedure, while a normal approximation uses a simplified distribution to estimate uncertainty or planning requirements. Neither establishes that an observed association is causal. The planning illustration does not replace the missing primary outcome result, nor does it provide an analysis plan for handling missing data, multiple endpoints, or differences among study groups. Those details are not reported in the registry record.

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("Part 1: Sonrotoclax 160 mg (Daily Ramp-up)", "Part 1: Sonrotoclax 320 mg (Daily Ramp-up)")
n      <- c(4, 4)
events <- c(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  Part 1: Sonrotoclax 160 mg (Daily Ramp-up)  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Part 1: Sonrotoclax 320 mg (Daily Ramp-up)  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2

11. Multiplicity, Missing Data and Analysis Populations

The study lists a primary Part 1 endpoint and multiple secondary outcomes, including pharmacokinetic measures and an independent-review-committee overall response rate. When a study evaluates several outcomes, multiplicity can arise because repeated testing increases the chance of at least one apparently positive result under a set of null hypotheses. In general, a prespecified strategy may control that risk, for example by defining a hierarchy or adjusting inference across selected outcomes. The registry record does not report a multiplicity-control strategy, testing hierarchy, or which outcomes would receive confirmatory interpretation.

The record also does not report how missing endpoint data, incomplete assessments, withdrawals, or participants who discontinue before the end of the DLT window were handled. In general, missingness can affect interpretation when the chance that an outcome is unobserved is related to health status, toxicity, or treatment exposure. A defined analysis population and transparent rules for incomplete follow-up help readers understand who contributes to each result. The DLT-evaluable-set description gives dose-exposure and safety-evaluation conditions, but its text is incomplete and the observed endpoint result is not reported.

The record identifies the DLT-evaluable set for the primary endpoint, but does not report a full analysis-population strategy across endpoints. It does not specify whether efficacy outcomes were assessed in all enrolled participants, a treated population, or another defined group. Nor does it report sensitivity analyses for missing data. These omissions prevent assessment of how population choices or incomplete observations might affect any outcome estimate.

The study is active, not recruiting, with a primary completion date of 2025-07-18. That status does not establish that the registry’s outcome reporting is complete. The analysis plan, missing-data methods, and multiplicity approach are not reported in the registry record and should not be inferred from the listed endpoints or the planning illustration.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaemia (10.0%), death (10.0%), covid-19 pneumonia (10.0%), pneumonia (10.0%), respiratory tract infection (10.0%).

The serious adverse-event figures count participants with at least one serious adverse event in each group: 6 of 10 in Part 1 at 160 mg with daily ramp-up, 5 of 12 in Part 1 at 320 mg with daily ramp-up, 14 of 43 in Part 2 at 320 mg with daily ramp-up, and 24 of 60 in Part 2 at 320 mg with twice-weekly ramp-up. The other-adverse-event counts are 10 of 10, 12 of 12, 42 of 43, and 51 of 60, respectively. The record lists 7, 9, 17, and 21 deaths in those groups, respectively.

These are group-specific descriptive counts, not evidence that the study drug caused the events or deaths. The groups were not randomized, differ in size and study part, and are not a like-for-like control comparison. The registry record does not report comparative adjustment or follow-up time by group. A raw count therefore cannot distinguish differences in risk from differences in group composition, exposure, or observation.

The serious adverse event terms listed at 10.0% each are anaemia, death, COVID-19 pneumonia, pneumonia, respiratory tract infection, and platelet count decreased. These registry-listed percentages should be read as reported, not as a causal attribution. Serious adverse events are also distinct from the Part 1 DLT endpoint, which applies its own event criteria and evaluation window. The DLT result is not reported in the registry record.

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

The record establishes that this is a non-randomized, open-label Phase 1/2 study of sonrotoclax monotherapy in relapsed or refractory mantle cell lymphoma. It describes the intended dose-finding role of Part 1, the efficacy assessment in Part 2, the DLT definition, and adverse-event counts across the listed groups. It also records pharmacokinetic outcomes and an independent-review-committee overall response rate among the secondary outcomes.

It does not report the primary DLT count, an overall response result, or a statistical estimate of treatment effect. As a result, the posted information cannot establish how frequently participants experienced DLTs under the endpoint definition, how responses were distributed, or how precisely an efficacy effect was estimated. The absence of those results in the registry record is not evidence that an outcome did or did not occur.

The safety counts document participants with recorded serious and other adverse events and the listed deaths in each group. They do not establish causation. Nor can the different counts be used to claim that one dose or ramp-up schedule is safer than another: allocation was non-randomized, the groups are not like-for-like controls, and the record does not report an adjusted comparative analysis. The listed serious-event terms do not replace a full accounting of event timing, severity, attribution, and exposure.

In general, a result’s meaning depends on the endpoint definition, the population analyzed, completeness of follow-up, and the uncertainty around estimates. Those elements are important in this study because the primary outcome is restricted to a defined early-treatment window and an evaluable population. The record’s endpoint description is partly truncated, and the result itself is not reported. The appropriate interpretation is therefore limited to design and descriptive safety reporting, rather than a conclusion about clinical benefit or comparative safety.

14. Why This Trial Matters Statistically

This trial illustrates why a clear distinction between dose-finding and efficacy questions matters. Part 1’s primary endpoint is a defined early-window DLT count intended to inform dose selection. Part 2 is described as an efficacy evaluation at the recommended Phase 2 dose. These aims concern different outcomes and populations; a safety endpoint in Part 1 cannot stand in for an efficacy result in Part 2.

It also highlights the limits of interpreting multiple groups when treatment assignment is non-randomized. Differences in recorded events across doses or ramp-up schedules may attract attention, but the groups are not equivalent controls. Without random allocation and a reported comparative analysis, raw counts do not isolate the effect of dose or schedule from differences among participants, exposure, and follow-up.

The registry’s DLT definition makes another statistical point: endpoint rules shape the result. The specified window, toxicity grades, alternative-cause condition, and exceptions for events that resolve within stated periods determine what counts. A participant-level count is meaningful only alongside a clear denominator and a transparent evaluable-population rule. Here, the DLT-evaluable description is incomplete and the observed count is not reported.

Finally, the record separates planned outcomes from posted findings. Listing an independent-review-committee response endpoint or pharmacokinetic measures does not itself provide their results. Likewise, a planning illustration using a stated significance level and allocation assumption does not describe the trial’s actual design or establish observed power. These distinctions support cautious, statistically grounded reading of an early-phase study record.

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 main limitation for interpreting the posted outcomes is that the registry record does not report the primary DLT result or the listed efficacy result. Without those findings, the study’s stated primary and efficacy questions cannot be answered from this record. No uncertainty estimate for the primary endpoint is reported either.

The design further limits comparisons among groups. Allocation is non-randomized, masking is absent, and the registry cautions that arms are not a like-for-like control comparison. Group-level adverse-event counts cannot establish the relative effect of the target doses or ramp-up schedules. The record does not report a comparative adjustment strategy, participant characteristics by group, or follow-up time by group.

The primary endpoint definition is detailed but the DLT-evaluable population description is truncated. This limits certainty about the full eligibility and analysis rules for that endpoint. The record does not report missing-data methods, the broader analysis populations, multiplicity procedures, or the statistical model used for primary and secondary outcomes. The sample-size illustration is not the protocol’s own design justification, which is not reported in the registry record.

Some arm descriptions also end mid-sentence, leaving their full stopping language unavailable in the registry record. The study is listed as active, not recruiting, with a primary completion date of 2025-07-18; that status does not imply that every outcome has been reported. These limitations call for separating the trial’s stated purpose and observed descriptive safety counts from unreported endpoint results and unsupported causal comparisons.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Sonrotoclax (BGB-11417) Monotherapy in Participants With Relapsed or Refractory Mantle Cell Lymphoma — NCT05471843.
• Registry record last updated 2026-09-22; status last verified 2026-08.
• Results first posted 2026-09-22.
• 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

NCT05471843 is a multicenter Phase 1/2, non-randomized, open-label study of sonrotoclax monotherapy in relapsed or refractory mantle cell lymphoma. The registry lists enrollment of 125 and a status of active, not recruiting. Part 1 is intended to assess safety and tolerability and inform dose selection; Part 2 evaluates efficacy at the recommended Phase 2 dose.

The primary endpoint is the Part 1 count of participants experiencing DLTs from the first ramp-up dose through the first 3 weeks at the target dose, approximately 7 weeks. Listed groups use target doses of 160 mg or 320 mg once daily, with daily or twice-weekly ramp-up schedules as described. Secondary outcomes include pharmacokinetic measures and independent-review-committee overall response rate.

The record gives descriptive adverse-event counts, but the primary DLT result and efficacy result are not reported in the registry record. Because allocation is non-randomized and the groups are not like-for-like controls, their counts do not support causal comparisons among doses or schedules.