Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL) (NCT03206970), a na phase 2 study. The primary outcome is Overall Response Rate (ORR) As Assessed By Independent Review Committee.

2. Clinical Question

3. Trial Design

This was a Phase 2, single-arm, open-label, multicenter study of zanubrutinib in participants with relapsed or refractory mantle cell lymphoma. The registry lists an enrollment of 86. The study began on 2017-03-02, had primary completion on 2019-02-15, and is marked completed. BeiGene is listed as the sponsor.

The intervention was zanubrutinib, administered orally at 160 milligrams twice daily. Because the study had a single group and no randomized allocation, the design describes outcomes among participants receiving the study drug; it does not estimate a randomized treatment contrast. There is no concurrent control arm against which to assess whether observed outcomes differ from outcomes under another treatment or a comparison condition.

The primary objective was to evaluate efficacy in participants with centrally confirmed relapsed or refractory MCL. The primary endpoint was ORR assessed by an independent review committee. Secondary outcomes listed in the registry include progression-free survival, time to response, duration of response, investigator-assessed ORR, and counts of participants experiencing treatment-emergent adverse events or adverse events leading to treatment discontinuation. The record lists seven outcome measures and two analyses, but does not identify the two analyses or give their statistical methods.

The study was open-label, so masking is listed as none. The registry record does not report a statistical analysis plan, the rationale for the enrollment target, interim analyses, or additional design details. These omissions limit what can be inferred about how the study was planned and how its findings were intended to be interpreted.

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: Safety Analysis Set: All participants who received any dose of study drug.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety Analysis Set: All participants who received any dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR) As Assessed By Independent Review Committee, measured over Up to 1 year and 11 months.

The primary endpoint was overall response rate (ORR) assessed by an independent review committee. It was defined as the percentage of participants whose best overall response was complete response (CR) or partial response (PR), using the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. Best overall response was the best response recorded from the start of zanubrutinib until data cut or the start of new antineoplastic treatment. Participants without a post-baseline response assessment, for any reason, were classified as non-responders for this endpoint.

ORR is a binary participant-level outcome: each participant is classified according to whether the specified response criterion was met. Reporting a proportion can describe how often the defined response occurred in the analyzed group. An independent review committee assessment provides an endpoint assessment separate from the investigator-assessed ORR listed among the secondary outcomes. It does not, by itself, establish a comparison with another treatment or resolve uncertainty about how the response proportion would differ in another population.

The timeframe is listed as up to 1 year and 11 months. The analysis population was the Safety Analysis Set, comprising participants who received any dose of study drug. The registry record does not report the number meeting the response definition, the ORR estimate, or a confidence interval. Thus, the endpoint definition is available, but its observed result and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: what an ORR estimate represents. A binary endpoint assigns each participant to one of two categories: meeting or not meeting the endpoint definition. ORR expresses the share of the analyzed population classified as having complete response or partial response. The registry record defines which responses count and which time period determines best overall response. It also specifies that a participant with no post-baseline response assessment is treated as a non-responder. Those rules determine how the endpoint is classified; they do not supply the observed result.

General: uncertainty around a proportion. A confidence interval describes the statistical uncertainty around an estimate under the method used to calculate it. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. The registry record does not report an ORR estimate or confidence interval, and it does not specify the method used to calculate uncertainty. Precision for the primary endpoint therefore cannot be evaluated from this record.

General: what a single-group study can estimate. In a single-group study, descriptive estimates characterize outcomes in the treated participants who were analyzed. A randomized comparison can estimate a difference between assigned groups under its design; a single-group study does not provide that direct contrast. Observed outcomes can also reflect factors other than the intervention, including participant characteristics and the course of illness. This general limitation applies to interpreting the single-arm design described in the registry record. No control-group estimate or comparative treatment effect is reported.

General: endpoint assessment. An independent review committee assessment and an investigator assessment are separate ways of evaluating response. The registry specifies independent review committee assessment for the primary ORR and lists investigator-assessed ORR as a secondary outcome. The record does not report the results of either assessment or give further detail about adjudication procedures. It is therefore not possible to compare the assessments or evaluate how they relate to each other.

General: missing response assessments. Missing outcome information can affect how an endpoint is interpreted. Here, the stated endpoint rule classifies participants without a post-baseline response assessment as non-responders, regardless of the reason. That rule makes the endpoint classification explicit, but the record does not give the number of participants without an assessment or describe additional sensitivity analyses. The impact of missing assessments on the reported endpoint cannot be evaluated without those details and the outcome results.

General: statistical significance and clinical interpretation. A p-value, when reported, addresses compatibility between observed data and a specified statistical model under a null hypothesis; it does not measure the size or importance of an effect. A confidence interval describes uncertainty in an estimate but does not by itself establish causation. The registry record does not report a primary endpoint p-value, confidence interval, or comparative effect. No claim about statistical significance can be drawn from the endpoint description alone.

Planning illustrations. The posted planning illustrations are based on the observed effect, use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns the total number of events; other illustrations concern participants per arm for 80% or 90% power. These are planning scenarios, not observed power and not the study's reported design justification. In particular, the equal-allocation, two-arm assumption does not describe the single-group design in this registry record. The registry record does not report its own sample-size justification or statistical plan.

General: over-dispersion and model assumptions. Over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, its uncertainty estimates may be too small. The primary outcome is described as a participant count for a binary response endpoint; the registry record does not identify a model for the primary analysis or report an over-dispersion assessment. Consequently, no model-specific conclusion about that issue can be made from this record.

The record lists two analyses but does not describe them. It also does not report the inferential procedure, handling of multiple analyses, interim monitoring, or analysis plan. These are relevant to understanding how estimates and tests were selected, but their absence should not be filled by assumptions about standard practice. The available record supports description of the stated endpoint rule, study structure, and listed safety counts; it does not support reconstruction of unreported statistical procedures.

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("Zanubrutinib")
n      <- c(86)
events <- c(72)
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  Zanubrutinib  86  72  83.7  74.2  90.8  74.5  90.0  74.5  90.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes, including progression-free survival, time to response, duration of response, investigator-assessed ORR, and adverse-event outcomes. It also lists seven outcome measures and two analyses. The record does not explain whether the analyses correspond to particular outcomes, nor does it report a multiplicity adjustment or a testing hierarchy. The approach to controlling the chance of false-positive findings across multiple statistical tests is therefore not reported in the registry record.

The primary endpoint definition includes a specific rule for participants without a post-baseline response assessment: they were considered non-responders for best overall response. The record does not state how many participants lacked such an assessment, whether other missing-data procedures were used for secondary outcomes, or whether sensitivity analyses were performed. The effect of missing assessments on the primary result cannot be assessed because the ORR result and missing-assessment count are not reported.

The primary population is the Safety Analysis Set, defined as all participants who received any dose of study drug. The registry record does not report additional analysis populations, exclusions, or how participants were handled in analyses of the secondary outcomes. It also does not report the statistical analysis plan, interim analyses, or a sample-size justification. These details are needed to understand the planned handling of multiple endpoints, missing observations, and analysis populations; they should not be inferred from the endpoint listings.

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: pneumonia (11.6%), upper gastrointestinal haemorrhage (2.3%), death (2.3%), platelet count decreased (2.3%), anaemia (1.2%).

The registry lists 25 participants with a serious adverse event among 86 at risk in the zanubrutinib group. It lists other adverse events for 82 among 86 at risk, and seven deaths. These figures describe the group in the registry record; they are not a comparison with a control group. The record does not provide further detail about event timing, duration, participant-level overlap among event categories, or the circumstances of the deaths.

The serious adverse event terms listed include pneumonia at 11.6%, upper gastrointestinal haemorrhage at 2.3%, death at 2.3%, platelet count decreased at 2.3%, anaemia at 1.2%, and bone marrow necrosis at 1.2%. The record does not describe the calculation details for these term percentages in this entry. The death term listed among serious adverse event terms is not the same presentation as the separate count of deaths; neither figure establishes causation.

Serious adverse event counts should be read as safety descriptions, not as evidence that an event was caused by treatment. The record does not report a comparative safety estimate, and the single-arm design offers no concurrent control group for comparison.

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

The record establishes that this completed Phase 2 study evaluated zanubrutinib in participants with relapsed or refractory MCL and defined a primary response endpoint assessed by an independent review committee. It also describes the endpoint classification rule, including how participants without a post-baseline response assessment were classified. The record lists safety counts and selected serious adverse event terms.

Those details do not reveal the observed primary ORR. The number of participants meeting the response definition, the response proportion, and its statistical uncertainty are not reported in the registry record. The listed endpoint and study objective cannot be treated as evidence of a particular result. Secondary outcomes are named, but their values are not reported in the registry record either.

The study was single-arm and open-label, with no randomized comparator. Accordingly, the registry information does not provide a randomized estimate of how outcomes differ between zanubrutinib and another treatment or comparison condition. Descriptive outcomes in a treated group do not by themselves establish that treatment caused those outcomes. Nor does the safety count establish that the study drug caused any listed adverse event or death.

The record can support a description of the study's design, dose, endpoint definition, analysis population, and safety reporting. It cannot support a quantitative conclusion about the primary efficacy result, the precision of that result, or comparative efficacy and safety. Those distinctions are important: knowing what a study set out to measure is different from having the result and the uncertainty needed to interpret it.

14. Why This Trial Matters Statistically

This study is statistically notable in the way its question and design need to be read together. The primary endpoint is a defined response proportion, assessed by an independent review committee, in a single group of participants. That can describe the frequency of the specified response among analyzed participants, but without a concurrent control group it does not estimate a randomized contrast.

The endpoint definition also makes the handling of unassessed responses explicit: participants without a post-baseline assessment were classified as non-responders. This is important because endpoint rules shape the quantity being estimated. Yet the registry record does not report how many participants were affected by that rule, or the resulting ORR, so its practical effect cannot be evaluated from the available record.

The record illustrates why statistical interpretation requires more than an outcome label. The primary result, confidence interval, p-value, analysis plan, and multiplicity approach are not reported in the registry record. The single-group design and the absence of these statistical details constrain conclusions about effect size, precision, and comparison. The listed safety counts likewise describe events in the study group without establishing causation or offering a concurrent reference group.

Finally, the planning illustrations rely on a two-arm equal-allocation scenario, whereas the study itself is described as single group. They are planning illustrations rather than observed power or a record of the trial's own design rationale. Keeping the trial design separate from such hypothetical planning scenarios helps avoid treating a calculated planning quantity as an observed finding.

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 limitation for interpreting efficacy is that the registry record does not report the primary ORR result. It supplies the endpoint definition and population but not the number of participants with complete or partial response, the estimated proportion, or an uncertainty interval. The listed secondary outcomes also lack reported results in this record.

The single-arm design has no concurrent randomized comparator. This prevents a direct randomized estimate of differences in outcomes between zanubrutinib and another treatment or comparison condition. The study is also open-label, with masking listed as none; the record does not describe further procedures that might address possible assessment or conduct biases. Independent review committee assessment is specified for the primary response endpoint, but the committee procedures and results are not reported.

The record does not report participant characteristics, detailed eligibility criteria, the number without post-baseline response assessment, or sensitivity analyses for missing data. It does not give a statistical analysis plan, the methods used for the two listed analyses, a multiplicity approach, interim analyses, or the sample-size justification. These gaps limit evaluation of the planned analysis and the robustness of any result.

The safety information is also limited to counts and selected terms. The registry record does not provide a comparative safety analysis or enough detail to assess timing, duration, overlap, or causality. The planning illustrations use a two-arm equal-allocation scenario and should not be mistaken for the trial's single-group design or its observed power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate Efficacy and Safety of BGB-3111 in Participants With Relapsed or Refractory Mantle Cell Lymphoma (MCL) — NCT03206970.
• Registry record last updated 2024-10-26; status last verified 2024-10.
• Results first posted 2020-05-13.
• 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

NCT03206970 is a completed, multicenter, open-label Phase 2 single-arm study sponsored by BeiGene. It evaluated zanubrutinib, administered orally at 160 milligrams twice daily, in participants with relapsed or refractory MCL. Enrollment is listed as 86; the study began on 2017-03-02 and primary completion was on 2019-02-15.

The primary endpoint was independent review committee-assessed ORR, defined by complete or partial response under the 2014 modification of the International Working Group on non-Hodgkin Lymphoma Criteria. The primary population was the Safety Analysis Set, and participants without a post-baseline assessment were considered non-responders. The registry record does not report the primary ORR result or its statistical uncertainty.

The record lists 25 participants with a serious adverse event among 86 at risk, 82 with other adverse events among 86 at risk, and seven deaths. These descriptive safety figures do not establish causation or provide a randomized comparison.