Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma (NCT03145064), a na phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

3. Trial Design

This was a phase 2, multicenter, open-label, single-group study of zanubrutinib in relapsed or refractory non-GCB type diffuse large B-cell lymphoma. The registry lists 41 enrolled participants and marks the study as completed. Because there was no comparator group, the design describes outcomes among participants who received zanubrutinib rather than a treatment contrast against a control.

The intervention was zanubrutinib, administered twice daily. The registry describes screening for up to 28 days, treatment until a specified stopping event or study termination, and treatment for up to 2 years. Safety follow-up was 30 days, while survival follow-up continued until the data cutoff for final analysis. The primary outcome timeframe was up to approximately 23 months. These are distinct descriptions of treatment and outcome follow-up; the record does not give participant-level follow-up durations.

The record says the Safety Analysis Set included all participants who received any dose of study drug and was used for efficacy and safety analyses. It does not separately describe a population used for the primary outcome beyond that definition. Since the study was open-label and response was determined by investigators, assessment was not masked according to the registry record.

The registry lists progression-free survival, duration of response, time to response, and treatment-emergent adverse events and serious adverse events among the secondary outcomes. It identifies 6 outcome measures, while no analysis records are listed. Detailed statistical methods, including any prespecified model or adjustment procedure, are not reported in the registry record. The study dates are listed as a start on 2017-06-30 and primary completion on 2019-05-24.

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: The Safety Analysis Set, which included all participants who received any dose of study drug, was the analysis set used for the efficacy and safety analyses.

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 Overall Response Rate, measured over Up to approximately 23 months.

Overall response rate is the percentage of participants who achieve either a complete response or a partial response. In this study, investigators assessed response using the 2014 modification of the International Working Group criteria for non-Hodgkin lymphoma. The registry identifies this as the primary outcome and gives an assessment timeframe of up to approximately 23 months.

As a general statistical concept, a response rate reduces an outcome to a binary classification for each participant: meeting the response definition or not meeting it. The proportion can communicate how often a defined response was observed in the analysis population, while a confidence interval conveys uncertainty around the estimated proportion. The registry lists a 95% confidence interval as the measure of dispersion for this endpoint, but its numerical estimate and interval are not reported in the registry record.

Response rate is used in clinical studies because it gives a direct summary of tumor response under stated assessment criteria. It does not, by itself, describe how long a response lasts, how long participants remain free of progression, or how outcomes compare with an alternative treatment. The registry lists duration of response, progression-free survival, and time to response as secondary outcomes, but their numerical results are not reported in the record. The outcome definition and assessment method therefore establish what the primary measure was intended to capture, but they do not establish its observed value.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design determines which statistical claims the data can support. This was a phase 2, single-group, open-label study. A single-group design can describe outcomes observed among participants receiving the intervention, but it does not estimate a randomized contrast against a concurrent comparator. Open-label means the study was not masked, as recorded in the registry. The record does not report an adjusted comparative analysis or an analysis plan that would change these basic design limits.

What does overall response rate represent?

The primary endpoint classifies participants according to whether they achieved a complete or partial response under the stated investigator-assessed criteria. Overall response rate is the percentage of the analysis population meeting either response category. The registry specifies the 2014 modification of the International Working Group criteria for non-Hodgkin lymphoma and a timeframe of up to approximately 23 months. It also names the Safety Analysis Set as the analysis population for efficacy and safety. The numerical rate, its confidence interval, and the response counts are not reported in the registry record.

As a general statistical explanation, a percentage is an estimate of the frequency of a defined event in a specified population. The choice of denominator matters: a percentage based on everyone enrolled could differ from one based on participants who received treatment or had an evaluable assessment. Here the registry defines the Safety Analysis Set as participants who received any dose, but it does not report the endpoint denominator or how missing assessments were treated. Thus, the endpoint definition alone is not enough to reproduce or independently check the estimate.

What does a confidence interval convey?

In general, a confidence interval expresses uncertainty in an estimated quantity under the assumptions of the statistical method. A narrower interval indicates greater precision than a wider interval, while neither interval width nor a point estimate alone establishes the clinical importance of a result. The registry specifies a 95% confidence interval for overall response rate, but it does not report the numerical interval or the method used to calculate it. Without those values, precision cannot be judged from the registry record.

The record does not state whether the interval used a normal approximation, an exact method, or another approach. That distinction can matter for a proportion, particularly when the data are limited or the estimated proportion is near a boundary. This is a general statistical consideration, not a statement about which method was used in this study.

Why does the single-group design matter?

A response proportion from a single group is a descriptive estimate for that group under the study’s eligibility, treatment, assessment, and follow-up conditions. In a randomized comparison, treatment groups can be compared under a design intended to balance prognostic factors on average. No such randomized comparison is available. Differences between an observed outcome and outcomes in other populations or studies could reflect differences in participants, care, assessment, follow-up, or other factors, rather than a treatment effect.

The study was open-label, and the primary outcome was investigator-determined. In general, lack of masking can influence assessments or decisions, depending on the endpoint and procedures. The registry does not report independent blinded review or other safeguards for response assessment, so those procedures are not reported in the registry record. This does not establish that assessments were biased; it identifies information needed to evaluate the assessment process.

How should the safety summaries be read?

The registry reports that 12 participants had a serious adverse event, with 41 at risk in the zanubrutinib group. It also reports 34 participants with other treatment-emergent adverse events and 24 deaths. The listed serious adverse event terms include pneumonia at 7.3%, death at 4.9%, abdominal infection at 2.4%, herpes zoster at 2.4%, chronic otitis media at 2.4%, and urinary tract infection at 2.4%. These summaries describe reported events; they do not identify treatment causation. The record does not explain whether participants could contribute to more than one listed term, and such categories should not be treated as mutually exclusive without that information.

General safety interpretation distinguishes the number of participants with an event from the number of event episodes, the seriousness classification, and the investigator’s assessment of relatedness. The registry’s counts are participant counts for the stated adverse-event summaries, while it does not provide detailed event-level timing, duration, severity, or relatedness for these figures. The death count should not be equated with the serious-event term Death, because the record gives these as separate summaries and does not report their relationship.

What can planning estimates tell the reader?

Sample-size calculations based on an observed effect are planning illustrations, not evidence about the study’s observed precision or a measure of observed power. General planning calculations depend on assumptions about the target effect, significance level, allocation, and statistical approximation. The stated assumptions for the illustrations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect; time-to-event illustrations use a total event count. Those assumptions describe hypothetical planning exercises rather than the design of this single-group trial. The record does not report that these calculations were the study’s own design justification.

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(41)
events <- c(12)
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  41  12  29.3  16.1  45.5  17.6  44.5  17.6  44.6

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the primary outcome as overall response rate and lists secondary outcomes that include progression-free survival, duration of response, time to response, and treatment-emergent adverse events and serious adverse events. It lists 6 outcome measures and no analysis records. A list of outcomes does not, by itself, establish how many formal hypotheses were tested or what inferential procedures were used.

Multiplicity is a general statistical concern when several outcomes or comparisons are tested. Without a prespecified testing hierarchy or adjustment procedure, repeated testing can increase the chance of a nominally noteworthy finding arising by chance. Whether such a concern applies to a particular claim depends on the analysis plan and the claims made. The registry does not report a multiplicity strategy, so it is not possible to determine from the record whether any adjustment was planned or used.

The record defines the Safety Analysis Set as all participants who received any dose of study drug, and says that set was used for efficacy and safety analyses. It does not report how missing outcome assessments, withdrawals, or incomplete follow-up were handled. For a response endpoint, missing assessments can affect the denominator or the classification of participants, depending on the analysis rules. The registry record does not state which rules were applied.

The record also does not report sensitivity analyses that would show how conclusions might change under alternative assumptions about missing outcomes. This lack of detail is not evidence that data were missing or that any particular method was used; those matters are not reported in the registry record. The absence of analysis records and a numerical primary outcome further limits assessment of the inferential procedure and of how the listed outcomes were interpreted.

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 (7.3%), death (4.9%), abdominal infection (2.4%), herpes zoster (2.4%), otitis media chronic (2.4%).

The registry reports 12 participants with a serious adverse event among 41 at risk in the zanubrutinib group. It reports other treatment-emergent adverse events in 34 participants and 24 deaths. These are separate safety summaries and should not be added together or interpreted as mutually exclusive groups. The record does not report whether participants could appear in more than one category or provide event-level overlap.

Among serious adverse event terms, the registry lists pneumonia at 7.3%, death at 4.9%, abdominal infection at 2.4%, herpes zoster at 2.4%, chronic otitis media at 2.4%, and urinary tract infection at 2.4%. These percentages describe the listed terms as recorded; they do not establish that the events were caused by zanubrutinib. The term Death at 4.9% is a serious-event term and should not be substituted for the separate count of 24 deaths, whose relationship to treatment is not reported in the registry record.

As a general principle, adverse-event summaries describe events occurring during a study, while attribution requires additional assessment. The registry record does not report detailed severity, timing, duration, or relatedness for these summaries, so those aspects cannot be inferred from the counts and terms alone.

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

The record establishes that a completed phase 2, open-label, single-group study evaluated zanubrutinib in participants with relapsed or refractory non-GCB type diffuse large B-cell lymphoma. It also defines the primary outcome as investigator-assessed overall response rate, based on complete or partial response under the stated criteria, over a timeframe of up to approximately 23 months. It reports an enrollment of 41 and describes the analysis population as participants who received any dose of study drug.

However, the registry record does not report the numerical overall response rate or its 95% confidence interval. Without those results, the primary outcome cannot be quantified, its precision cannot be assessed, and the record does not support a conclusion about the frequency of response in the study group. The missing estimate is not evidence for either a high or low response rate.

Even if a response estimate were available, the single-group design would describe outcomes in the enrolled study population rather than establish a comparative treatment effect. There was no comparator arm, and the study was open-label. Outcomes could not be attributed to zanubrutinib by comparing them with a randomized control group in this study. The registry also does not report details of response assessment safeguards or handling of missing assessments.

The safety summaries document serious adverse events, other treatment-emergent adverse events, deaths, and selected serious-event terms. They are useful descriptions of what the registry reports, but they do not alone determine causation, comparative safety, or the balance of benefits and harms. The record does not provide enough detail to link the separate death count to treatment or to the listed serious-event term Death.

Overall, the registry record supports statements about the study’s design, endpoint definition, follow-up framework, analysis population, and selected safety counts. It does not report the efficacy result needed to characterize the primary endpoint numerically, nor does it provide a controlled comparison from which a causal treatment contrast could be estimated.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clearly named endpoint and a completed study record do not necessarily provide enough information for outcome interpretation. The primary endpoint is defined, the assessment framework is stated, and the population used for analyses is described. Yet the numerical response estimate and its confidence interval are not reported in the registry record. Without those values, readers cannot assess the magnitude or precision of the primary result.

The study also illustrates the distinction between estimating an outcome within a treatment group and estimating a treatment contrast. A single-group study can describe the observed experience of its participants. It cannot provide a randomized comparison against a control group that was not included in the design. This design feature is important when interpreting any reported response or safety summary.

Another statistical consideration is the link between the outcome definition and analysis population. The registry specifies a Safety Analysis Set consisting of participants who received any dose, but does not report the endpoint denominator or the handling of missing assessments. These decisions affect how a proportion is interpreted and whether an estimate can be reproduced.

Finally, the safety summaries show why event counts need careful labels. The number of participants with serious adverse events, the count with other treatment-emergent adverse events, the death count, and percentages for particular serious-event terms describe different summaries. They should not be conflated or treated as evidence of causation in the absence of attribution information.

The central statistical lesson is that study design, endpoint definition, analysis population, numerical estimate, uncertainty, and reporting completeness all contribute to interpretation. The registry provides some of these elements, but does not report the primary numerical result or several analysis details needed for a fuller evaluation.

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 most direct limitation for interpreting this record is that it does not report the numerical primary outcome or its 95% confidence interval. The endpoint definition and timeframe are available, but the estimated overall response rate, response counts, and precision are not. This prevents a numerical assessment of the primary result.

The study was single-group, open-label, and had no comparator arm. Its design can describe outcomes in participants who received zanubrutinib, but it cannot make a randomized comparison with another treatment. The primary outcome was investigator-determined; the registry does not report whether independent or blinded review was used.

The record describes the analysis population as participants who received any dose of study drug, but does not report the primary endpoint denominator or how missing response assessments were handled. It also does not report details of analysis methods, sensitivity analyses, multiplicity procedures, or a statistical analysis plan. These items are not reported in the registry record, and their absence should not be interpreted as evidence that a particular procedure was or was not used.

Although selected safety counts and serious-event terms are listed, the record does not provide detailed event timing, severity, duration, or relatedness for the summaries. The separate count of deaths is not linked to the listed serious adverse event term Death. Consequently, the reported safety information does not establish causation or explain the relationship among those summaries.

The primary outcome timeframe was up to approximately 23 months, while the registry describes treatment up to 2 years and survival follow-up until the data cutoff for final analysis. Participant-level follow-up and outcome-specific completeness are not reported. Those missing details limit assessment of how consistently outcomes were observed across participants.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of BTK Inhibitor Zanubrutinib in Participants With Relapsed/Refractory Non-GCB Type Diffuse Large B Cell Lymphoma — NCT03145064.
• Registry record last updated 2024-10-26; status last verified 2024-10.
• Results first posted 2021-11-08.
• 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

The registry describes a completed phase 2, multicenter, open-label, single-group study of zanubrutinib in relapsed or refractory non-GCB type diffuse large B-cell lymphoma. It lists an enrollment of 41 and defines overall response rate, assessed by investigators under the 2014 modification of the International Working Group criteria for non-Hodgkin lymphoma, as the primary outcome.

The Safety Analysis Set included participants who received any dose of study drug and was used for efficacy and safety analyses. The registry reports serious adverse events in 12 participants, other treatment-emergent adverse events in 34 participants, and 24 deaths, along with selected serious-event terms. The numerical primary response rate and its 95% confidence interval are not reported in the registry record. The single-group design provides no randomized comparator.