BTK Inhibitor BGB-3111 in Chinese Participants With Diffuse Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BTK Inhibitor BGB-3111 in Chinese Participants With Diffuse Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL) (NCT03520920), a non-randomized phase 2 study. The primary outcome is Overall Response Rate (ORR) As Measured By The Investigator.

2. Clinical Question

3. Trial Design

This was a multicenter, open-label, phase 2 study of zanubrutinib plus rituximab in Chinese participants with relapsed or refractory lymphoma. The three disease groups were non-germinal center B-cell-like diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma. The record reports enrollment of 41 and lists the study as completed. The recorded study start was 2018-01-04, and primary completion was 2020-08-28.

The allocation was non-randomized, masking was none, and the model was single group. Participants were treated according to lymphoma type; the record describes separate groups for relapsed or refractory non-GCB DLBCL and relapsed or refractory FL or MZL. In both group descriptions, treatment continued up to progressive disease or intolerance. The listed dose was zanubrutinib 160 milligrams twice daily with rituximab.

Because there was no randomized control group, the design does not support a randomized treatment comparison. The disease groups also differ in diagnosis, so their outcomes should not be treated as if they were exchangeable treatment arms. The registry record does not report the number of study centers, the duration of individual follow-up, or details about how participants entered each disease group.

The primary outcome was investigator-assessed overall response rate, defined by best overall response meeting partial response or complete response criteria. The timeframe was up to approximately 2.5 years. Listed secondary outcomes include duration of response, progression-free survival, overall survival, time to response, and event-free or survival rates. Numerical results for these outcomes 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: Safety Analysis Set included all participants who received at least 1 dose of study drug (zanubrutinib or rituximab) on the study.

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 (ORR) As Measured By The Investigator, measured over Up to approximately 2.5 years.

The primary endpoint is the investigator-assessed overall response rate (ORR), expressed as the percentage of participants whose best overall response met partial response or complete response criteria. Its stated timeframe was up to approximately 2.5 years. The analysis population was the Safety Analysis Set: all participants who received at least 1 dose of zanubrutinib or rituximab on the study.

In general, a response endpoint reduces a participant’s pattern of tumor assessments to a categorical summary: whether the recorded best response reached one of the specified response categories. A proportion can describe how common that response classification was in the defined analysis population. It does not, by itself, describe how long a response lasted, whether disease later progressed, or how outcomes compare with another treatment.

The registry specifies a 95% confidence interval calculated with the Clopper-Pearson method. That interval is intended to show uncertainty around the estimated response proportion. However, the numerical ORR and confidence interval are not reported in the registry record. Consequently, the primary endpoint definition is available, but its observed estimate and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint count?

The primary endpoint is an overall response proportion. For each participant in the Safety Analysis Set, the best overall response was classified, and the endpoint counts those whose classification met partial response or complete response criteria. In general, a proportion is the number of participants meeting a defined condition divided by the number of participants in the specified population. The registry defines the condition and population, but it does not report the observed count or estimate.

The endpoint uses the best overall response rather than a single assessment. That is the endpoint definition in the registry; the assessment schedule, response-assessment rules, and handling of participants without an evaluable response are not reported in the registry record. The result timeframe is stated as up to approximately 2.5 years, but the record does not give individual follow-up durations.

What does a confidence interval add?

A confidence interval gives a range of values compatible with the observed data under a statistical method and its assumptions. In general, a 95% confidence interval is constructed so that, over repeated studies conducted under the same conditions, intervals produced by the method would cover the fixed underlying quantity at the stated rate. It is not a guarantee that a particular interval contains the true value, and it does not account automatically for limitations such as non-randomized enrollment or incomplete outcome information.

The registry says the ORR interval was calculated with the Clopper-Pearson method. In general, this is an exact binomial method for an event proportion. It is often used when event counts are limited because it does not rely on the same large-sample approximation used by some other proportion intervals. Its exact construction does not remedy missing outcome results: without the response count and analysis denominator, the interval cannot be interpreted from the registry record.

What does the design allow statistically?

The study is described as phase 2, open-label, non-randomized, and single group. In general, a single-group study can describe observed outcomes among enrolled participants, but it cannot provide a randomized contrast against a concurrent control. Without random allocation, differences from outcomes in another population or study can be affected by differences in eligibility, disease mix, follow-up, assessment, and other features. Those comparisons are not equivalent to a controlled treatment-effect estimate.

Open-label means masking was listed as none. In general, when treatment assignment is known, subjective decisions or assessments can be influenced by awareness of treatment. The record says the primary outcome was investigator-assessed, but it does not report any additional safeguards or independent review process. Their use should not be assumed.

How should planning calculations be understood?

General sample-size planning asks how many participants might be needed to detect a specified effect under chosen assumptions. The planning description associated with this record specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event outcomes, the planning description refers to a total number of events, while other outcomes use participants per arm.

These are planning assumptions, not evidence that the trial used a two-arm randomized design. The actual study is recorded as single group and non-randomized. No numerical planning results, assumed observed effect, or trial-specific sample-size justification are reported in the registry record. Any planning illustration based on an observed effect is not an observed-power calculation and should not be read as the study’s original design rationale.

What can be inferred from the recorded analysis information?

The record lists 11 outcome measures and 0 analyses. These entries do not supply numerical results for the primary or secondary endpoints. The listed secondary outcomes include duration of response, progression-free survival, overall survival, time to response, and related event-free or survival rates. For time-to-event outcomes, general interpretation depends on event counts, follow-up, censoring, and the analysis method. Those numerical estimates and methods are not reported in the registry record.

Statistical interpretation therefore stops at the available definitions and counts. The specified endpoint method is known for ORR, but the observed ORR is not. Analysis methods for the other listed outcomes, adjustment for covariates, and handling of incomplete observations are not reported in the registry record. The absence of those details prevents reconstruction or independent assessment of those analyses.

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("Relapsed/Refractory Non-germinal Center B-cell-lik", "Relapsed/Refractory Follicular Lymphoma", "Relapsed/Refractory Marginal Zone Lymphoma")
n      <- c(20, 16, 5)
events <- c(7, 9, 3)
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  Relapsed/Refractory Non-germinal Center B-cell-lik  20  7  35.0  15.4  59.2  18.1  56.7  18.1  57.0
ARM  Relapsed/Refractory Follicular Lymphoma  16  9  56.2  29.9  80.2  33.2  76.9  32.9  77.0
ARM  Relapsed/Refractory Marginal Zone Lymphoma  5  3  60.0  14.7  94.7  23.1  88.2  22.3  88.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary ORR and secondary outcomes such as duration of response, progression-free survival, overall survival, and time to response. It does not report a multiplicity strategy in the registry record. In general, assessing several outcomes can increase the chance that at least one result appears notable by chance if each is tested separately. Methods such as prespecifying a hierarchy or adjusting significance thresholds can address that issue, but their use in this study is not reported and should not be assumed.

The record lists 0 analyses and provides no numerical primary or secondary outcome results. This means there are no registry-reported estimates or inferential results to evaluate for multiplicity. It does not establish whether analyses were conducted elsewhere or whether a multiplicity plan existed; those matters are not reported in the registry record.

The primary outcome population is defined as all participants who received at least 1 dose of zanubrutinib or rituximab. The record does not report how missing, unevaluable, or incomplete response assessments were handled, nor does it provide participant-level outcome completeness. The approach to missing data for the secondary outcomes is also not reported in the registry record.

In general, missing-data methods matter because an analysis can depend on how participants without an observed outcome are classified or otherwise handled. Without the number and pattern of missing assessments and the analysis rules, the direction or size of any possible influence cannot be determined. Other analysis populations, including any intent-to-treat or per-protocol population, are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnoea (10.0%), abdominal pain (10.0%), lymphangitis (6.2%), pneumonia (6.2%), pulmonary mycosis (6.2%).

The adverse-event figures are presented separately for the three disease groups. Serious adverse events affected 7 of 20 participants with relapsed or refractory non-GCB DLBCL, 4 of 16 participants with relapsed or refractory FL, and 0 of 5 participants with relapsed or refractory MZL. Other adverse events affected 19 of 20, 16 of 16, and 5 of 5 participants in those respective groups. The listed deaths were 13, 1, and 0, respectively.

These are group-specific descriptive counts, not comparisons between randomized treatment arms. The group sizes differ, and each group represents a different lymphoma population. Serious adverse events and other adverse events are separate reported categories; the record does not provide enough detail to infer overlap between them or to characterize event severity beyond the serious-event classification.

The registry lists dyspnoea and abdominal pain at 10.0% each among the top serious adverse-event terms, and lymphangitis, pneumonia, pulmonary mycosis, and pleural effusion at 6.2% each. The record does not state the group-specific denominators for these listed term percentages in the available information. It also does not report the causes or timing of deaths, or whether events were considered related to treatment. The counts alone do not establish causation.

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

The study was designed to assess safety, tolerability, and activity of zanubrutinib with rituximab in Chinese participants with relapsed or refractory non-GCB DLBCL, FL, or MZL. The registry defines investigator-assessed ORR as the primary outcome, with partial response or complete response as the response categories. However, the numerical ORR and its 95% confidence interval are not reported in the registry record. The primary efficacy result therefore cannot be described from the recorded information.

The record does provide adverse-event counts by disease group. Those counts describe how many participants were recorded as having serious adverse events, other adverse events, or deaths in each group. They do not establish that the study drugs caused those events. The record does not provide event timing, cause of death, treatment attribution, or detailed follow-up for these counts.

In general, an observed response proportion from a single-group study describes outcomes among the participants studied. It does not determine what would have happened to comparable participants under another treatment. This distinction is especially important because the study had no randomized comparator and included three different lymphoma populations. The trial record cannot support a randomized estimate of treatment benefit relative to another option.

Likewise, the phase 2 label and endpoint definitions do not substitute for numerical findings. A confidence interval would help describe precision around an observed proportion, but no interval is reported. Secondary outcomes are named, but their numerical results and analysis methods are not reported in the registry record. The defensible interpretation is limited to the study design, stated endpoint, and recorded adverse-event counts; efficacy magnitude, comparative effects, and the precision of any efficacy estimate remain unknown from this record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design determines the questions that results can answer. It was an open-label, non-randomized, single-group phase 2 study. Those features permit descriptive assessment of outcomes among enrolled participants, but they do not create a randomized control comparison. The three lymphoma groups are clinically defined populations, not interchangeable arms for estimating a treatment contrast.

The primary outcome definition is specific: investigator-assessed best overall response meeting partial response or complete response criteria, in participants who received at least 1 dose of either study drug. The registry also specifies a Clopper-Pearson 95% confidence interval. These details identify the intended outcome and uncertainty method. Yet the registry does not report the resulting ORR or interval. The distinction between a defined analysis and a reported estimate matters: a prespecified endpoint cannot be interpreted numerically without its outcome data.

The registry lists secondary time-to-event outcomes as well as response outcomes, which raise different statistical questions. In general, survival and duration endpoints depend on follow-up and event information, while response proportions summarize a categorical outcome. The record does not give numerical estimates or analysis details for these secondary measures, so their interpretation is not possible from the registry record.

The safety entries also illustrate why denominators and context matter. Counts are separated by disease group, with different group sizes, and deaths are listed without cause or treatment attribution. Such observations are useful for describing what was recorded, but they cannot establish causation or provide a randomized safety comparison. Taken together, the record supports a careful reading of endpoint definitions and design limits, while leaving efficacy estimates and their precision unreported.

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 trial-specific limitation for statistical interpretation is the absence of numerical results for the primary ORR endpoint. Although its response definition, analysis population, timeframe, and confidence-interval method are stated, the registry record does not report the observed estimate or interval. Numerical results for the listed secondary outcomes are also not reported.

The design was non-randomized, open-label, and single group. There was no like-for-like randomized control group, so the record cannot support a randomized estimate of comparative efficacy or safety. The three disease groups also represent different lymphoma types; their outcomes should not be treated as directly comparable treatment arms.

Enrollment was 41 overall, while the safety-event information is separated into groups of 20, 16, and 5 participants. The record does not describe how participants were allocated among the disease groups beyond their diagnoses, nor does it provide further detail on eligibility or group-specific follow-up. The small group sizes make descriptive counts particularly important to interpret as counts rather than as stable comparative estimates.

The registry does not report the number or pattern of missing outcome assessments, rules for handling participants without an evaluable response, analysis methods for secondary outcomes, multiplicity control, or adjusted analyses. It also does not report causes or timing of deaths or treatment attribution for adverse events. These omissions limit assessment of outcome completeness, uncertainty, and possible sources of bias. They do not establish that such methods or information were absent from all study documents; they are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BTK Inhibitor BGB-3111 in Chinese Participants With Diffuse Large B-Cell Lymphoma (Non-GCB) and Indolent Lymphoma (FL and MZL) — NCT03520920.
• Registry record last updated 2024-10-26; status last verified 2024-10.
• Results first posted 2021-10-28.
• 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

NCT03520920 is a completed, multicenter, open-label phase 2 study of zanubrutinib, at 160 milligrams twice daily, with rituximab in Chinese participants with relapsed or refractory non-GCB DLBCL, FL, or MZL. The registry reports enrollment of 41, non-randomized allocation, no masking, and a single-group model. Treatment was described as continuing until progressive disease or intolerance.

The primary outcome was investigator-assessed ORR, defined by best overall response meeting partial response or complete response criteria, with a stated 95% Clopper-Pearson confidence interval and a timeframe of up to approximately 2.5 years. Its numerical result and interval are not reported in the registry record. The record lists secondary response and time-to-event outcomes but does not report their numerical results. It provides serious and other adverse-event counts, along with deaths, by disease group; causes, timing, and treatment attribution are not reported.