To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL) (NCT04661007), a non-randomized phase 1, phase 2 study. The primary outcome is Phase 1, Parts 1 and 2; Number of Participants With Any Treatment-emergent Adverse Event (TEAE).

2. Clinical Question

The study is intended to characterize safety and tolerability, support selection of recommended phase 2 doses, and evaluate combination regimens in the stated participant groups. The primary outcome is a count of participants with any treatment-emergent adverse event, rather than a comparison of treatment efficacy between randomized arms. Adverse events include medical occurrences temporally associated with study treatment whether or not considered drug related.

The registry lists secondary outcomes that include tafasitamab maximum and minimum concentrations, investigator-assessed response under Lugano criteria, change in measured lesions, complete response assessed by an independent review committee, and duration of response. These outcomes address different questions and apply to specified study parts; they should not be treated as one common endpoint across all groups. The registry record does not report a randomized treatment comparison or an efficacy result that establishes whether one regimen is better than another.

3. Trial Design

This is an open-label, multicenter phase 1b/2 study with nonrandomized allocation and a parallel-group model. The registry lists enrollment of 72 and describes Japanese participants with non-Hodgkin lymphoma, including diffuse large B-cell lymphoma. The record gives a start date of 2020-12-15, a primary completion date of 2025-07-01, and an active, not recruiting status.

Part 1 evaluates tafasitamab monotherapy using weight-based doses in one group, with dose-finding intended to assess safety and tolerability and determine recommended phase 2 doses. Part 2 evaluates combinations: tafasitamab with lenalidomide or parsaclisib in relapsed or refractory diffuse large B-cell lymphoma, and tafasitamab with lenalidomide plus R-CHOP in previously untreated diffuse large B-cell lymphoma. A further lenalidomide combination group is described with modified tafasitamab dosing. Part 3 expands evaluation of tafasitamab plus parsaclisib at the recommended phase 2 dose determined in Part 2. Part 4 further evaluates tafasitamab plus lenalidomide at its recommended phase 2 dose.

The posted group sizes differ: the phase 1 groups listed in the adverse-event results each have six participants at risk, while the phase 2, part 4 group has 42. The registry does not describe random allocation, masking, or a concurrent control regimen; masking is listed as none. Because the groups have different regimens and include distinct disease settings and study parts, their outcomes should be read as group-specific descriptive findings, not as estimates from a controlled comparison.

The primary outcome is listed for phase 1, parts 1 and 2. Other outcomes cover additional study parts and include pharmacokinetic measures and response assessments. The registry record does not report the rationale for the enrollment target, the detailed dose-escalation algorithm, or a full statistical analysis plan. Those details should not be inferred from the group structure or the posted counts.

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: Part 3 was planned to consist of 1 dose-expansion group to further evaluate the safety, tolerability, and preliminary antitumor activity of the recommended Phase 2 dose deemed safe and tolerable in Part 2 for the combination of tafasitamab and parsaclisib. Based on the sponsor's decision, participants for Part 3 were not recruited.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population: all participants who received at least 1 dose of study treatment. Adverse events were collected for the treatment group to which participants were assigned, not according to the dose participants were receiving following dose adjustments within each treatment group.

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.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Phase 1, Parts 1 and 2; Number of Participants With Any Treatment-emergent Adverse Event (TEAE), measured over up to 1066 days.

The named primary endpoint is the number of participants with any treatment-emergent adverse event in phase 1, parts 1 and 2. An adverse event is defined as an untoward medical occurrence associated with use of a drug in humans, whether or not considered drug related. It may be an unfavorable or unintended sign, including an abnormal laboratory finding, symptom, or disease that is new or worsened and temporally associated with study treatment.

A treatment-emergent adverse event is defined as a new adverse event or worsening of an event from the first dose through 90 days after the last dose, with the record specifying 30 days until Amendment 3. The listed timeframe for this endpoint is up to 1066 days. The endpoint is a participant count: it records whether participants experienced an event within the defined observation window, rather than the total number of event episodes or a rate per unit of follow-up.

Safety outcomes of this kind are used in early-phase studies to characterize observed tolerability and identify events requiring further evaluation as doses and combinations are studied. The registry defines the safety population as participants who received at least one dose of study treatment. It also states that adverse events are assigned to the treatment group to which participants were assigned, not reclassified according to doses received after within-group dose adjustments.

The endpoint does not, by itself, establish that treatment caused an event. The definition includes events whether or not judged related to study treatment. Nor does a participant count describe event severity, duration, recurrence, or exposure-adjusted frequency. Those questions require additional results and analysis details; where such details are absent, they are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent? The primary outcome is a count of participants who experienced at least one treatment-emergent adverse event, not a count of every event episode. A participant with multiple events can still contribute once to a participant-level outcome. The registry defines the safety population as those who received at least one dose of study treatment and assigns events to the group to which participants were assigned, even if dose adjustments occurred within that group. These rules set the population and grouping for interpreting the endpoint.

Why does the observation window matter? A safety outcome depends on when events are counted. The record defines treatment-emergent events as new or worsening events from the first dose through 90 days after the last dose, with 30 days applying until Amendment 3. The stated primary-outcome timeframe is up to 1066 days. A longer observation period creates more opportunity to record an event, so counts are most meaningful when read with the stated window and the amount of follow-up. The registry record does not report individual follow-up times or an exposure-adjusted event rate for this endpoint.

What is the distinction between serious and other events? The posted safety results distinguish participants with serious adverse events from those with other adverse events. “Serious” is a separate classification from whether an event is considered related to treatment. The event definition explicitly includes occurrences whether or not they are judged drug related. The registry does not provide a causal assessment in the group counts, so a serious-event count should not be read as a count of events caused by treatment. Deaths are also listed, but the record does not identify in these results whether they were treatment-related.

Why is a randomized comparison important? Random allocation helps balance measured and unmeasured participant characteristics across treatment groups, on average, supporting a more credible causal comparison. This study is nonrandomized and has no like-for-like control group. Its arms differ by regimen, study part, and clinical setting. Consequently, a raw difference in counts between groups would combine possible treatment effects with differences in who entered each group, how long they were observed, and the treatment context. No causal effect estimate should be inferred from such a contrast.

What do uncertainty intervals usually add? In general, a confidence interval describes the range of values reasonably compatible with an estimate under a statistical model and its assumptions. It communicates precision, not the probability that a specific treatment effect is true. The registry record does not list confidence intervals for these safety counts. For small groups, estimates are generally imprecise, and a count alone does not convey that uncertainty. This is a general statistical point, not a reported trial result.

What is over-dispersion, and does it apply? In general, over-dispersion means observed variation exceeds what a chosen statistical model expects. It can matter for count outcomes when event counts vary more than assumed, because standard errors and intervals may then be too narrow if the model is not adapted. The primary endpoint is a participant count with at least one event, rather than a recurrent-event count. The registry does not report a model for over-dispersion or an inferential analysis of this endpoint, so no such model-based conclusion can be drawn.

How should the listed secondary outcomes be understood? They address different quantities. Cmax and Cmin are pharmacokinetic measures of maximum and minimum tafasitamab concentration. Response assessments use Lugano criteria, with some specified as investigator-assessed and a complete-response outcome in Part 4 assessed by an independent review committee. Duration of response is listed as a Kaplan-Meier estimate in Part 4. In general, Kaplan-Meier methods estimate time-to-event patterns while accounting for participants whose event time is not observed during follow-up, subject to assumptions about censoring. The registry record does not provide results or analysis details sufficient to assess those assumptions.

What can planning calculations say? In general, a sample-size planning illustration based on an observed effect describes a hypothetical future design under specified assumptions; it is not observed power and does not show that the present study was adequately powered. The planning assumptions stated for this record include a two-sided significance level of 0.05, equal allocation, a normal approximation, and effect fractions based on the observed effect. For time-to-event outcomes, the illustration refers to total events; for other outcomes, it refers to participants per arm. The record does not report that these planning assumptions were the trial’s own design or sample-size justification.

Which analysis choices remain unclear? The registry record does not report a full statistical analysis plan, the method for handling missing endpoint data, multiplicity control, or details of any interim analyses. It lists no statistical analysis results for the posted safety counts. These absences limit assessment of how estimates were generated and how uncertainty or multiple outcomes was handled. They should not be filled in by assumptions about common practice.

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("Phase 1, Part 1, Group 1: Tafasitamab Monotherapy", "Phase 1, Part 2, Group 2: Tafasitamab Plus Lenalid", "Phase 1, Part 2, Group 3: Tafasitamab Plus LEN", "Phase 1, Part 2, Group 4a: Tafasitamab Plus Parsac", "Phase 1, Part 2, Group 5: Tafasitamab Plus LEN Plu")
n      <- c(6, 6, 6, 6, 6)
events <- c(6, 6, 6, 6, 6)
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  Phase 1, Part 1, Group 1: Tafasitamab Monotherapy  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase 1, Part 2, Group 2: Tafasitamab Plus Lenalid  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase 1, Part 2, Group 3: Tafasitamab Plus LEN  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase 1, Part 2, Group 4a: Tafasitamab Plus Parsac  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Phase 1, Part 2, Group 5: Tafasitamab Plus LEN Plu  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes across study parts: safety, tafasitamab concentrations, investigator-assessed response, lesion reduction, complete response assessed by an independent review committee, and duration of response. When many outcomes are examined, multiplicity can increase the chance of at least one apparently notable result arising by chance. In general, an analysis plan may address this through prespecified testing order or other adjustment methods. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how any inferential testing across outcomes was controlled.

The record also does not report how missing endpoint observations were handled, whether participants with incomplete follow-up were included in particular analyses, or whether sensitivity analyses were conducted. For a safety count, incomplete observation can affect the opportunity to record an event. For response and duration outcomes, missing assessments and censoring can influence estimates. These are general concerns; the specific handling in this study is not reported in the registry record.

The primary endpoint population is defined as the safety population: all participants who received at least one dose of study treatment. Events are assigned to the group to which participants were assigned rather than the dose being received after dose adjustments within a group. The record does not provide further population definitions for every secondary outcome or a full account of exclusions from each analysis.

No interim analysis plan or detailed statistical analysis plan is reported in the registry record. The posted counts can therefore be described as reported, but the prespecified status of other analyses, missing-data procedures, and any multiplicity adjustments cannot be verified from this 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: covid-19 (16.7%), depressed level of consciousness (16.7%), diarrhoea (16.7%), liver disorder (16.7%), optic ischaemic neuropathy (16.7%).

The adverse-event results list participants at risk, participants with serious adverse events, participants at risk for other adverse events, participants with other adverse events, and deaths. In the total row, the record lists 72 participants at risk, 12 with serious adverse events, 72 at risk for other adverse events, 70 with other adverse events, and 8 deaths. These are participant counts, not event episode totals or exposure-adjusted rates.

Group results should be read separately. For example, the phase 1 monotherapy group lists six participants at risk and no participants with a serious adverse event; the phase 2, part 4 group lists 42 at risk and 8 with a serious adverse event. These are descriptive counts from different groups, not a controlled comparison. The death counts listed for the groups include 1 in the phase 1, part 2 group receiving tafasitamab plus LEN plus R-CHOP and 7 in the phase 2, part 4 group; the total row lists 8. The registry results do not state whether these deaths were attributed to treatment.

Serious-event terms are also reported with percentages. COVID-19, depressed level of consciousness, diarrhoea, liver disorder, and optic ischaemic neuropathy are each listed at 16.7%, while anaemia is listed at 2.4%. The registry record does not clarify the denominator or whether participants could contribute to more than one term. The term percentages therefore should not be combined or interpreted as a complete distribution of events.

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

The posted results describe safety observations in a nonrandomized, open-label study of tafasitamab alone and in combination regimens. They show counts of participants with serious and other adverse events in the listed groups, along with deaths and selected serious-event terms. These data can characterize what was recorded during the study’s defined safety observation period, but they do not by themselves establish that treatment caused an event.

The figures do not answer whether tafasitamab or any combination regimen is more effective than another treatment. There is no randomized control group, and the different groups are not like-for-like comparisons. The groups reflect different treatment combinations, study parts, and disease settings. An apparent difference in safety counts between groups cannot isolate the contribution of an individual drug or regimen.

The record’s primary outcome is a participant count for treatment-emergent adverse events in phase 1, parts 1 and 2. The posted serious and other adverse-event counts provide descriptive safety information, but do not supply a complete inferential analysis of that endpoint. No confidence intervals, p-values, adjusted comparisons, or full analysis plan are reported in the registry record. The count alone also does not describe event severity beyond the serious-event classification, duration, recurrence, or exposure-adjusted frequency.

Secondary outcomes listed for the study include pharmacokinetic measures and response assessments. Their presence in the registry does not establish a result: efficacy estimates and their precision are not stated in the registry record of this record. The record therefore supports a limited interpretation of observed safety counts and the trial’s intended questions, not a conclusion about comparative benefit or harm.

In general, early-phase findings can inform further investigation by describing safety experience and dose evaluation in the studied setting. They are not a substitute for a controlled comparison when the question is whether one regimen changes outcomes relative to another. The registry’s active, not recruiting status and listed primary completion date describe the study record’s administrative status and timeline; they do not, on their own, signal that a treatment effect has been established.

14. Why This Trial Matters Statistically

This trial is statistically notable for combining dose-finding and expansion questions across several treatment regimens within a nonrandomized design. Such a design can describe safety experience and support dose selection in the populations studied, but the design does not provide the balance achieved by randomization. Interpretation must therefore focus on group-specific observations rather than unadjusted comparisons across arms.

The study also illustrates why endpoint definitions matter. The primary safety outcome counts participants with at least one treatment-emergent adverse event, and the event window extends from first dose through a specified period after the last dose. That definition is distinct from counting all event episodes, classifying seriousness, or determining treatment attribution. Reading the result accurately requires keeping these concepts separate.

Group sizes are not uniform: the phase 1 groups listed in the safety results have six participants each, whereas the phase 2, part 4 group has 42. Counts from small groups can be sensitive to individual observations, and differences in group size affect how much information each count carries. The larger group does not resolve confounding or create a valid control comparison.

The record names a range of secondary outcomes, including pharmacokinetics and response measures. Multiple endpoints make it important to know the planned hierarchy, multiplicity approach, missing-data rules, and analysis populations. Those details are not reported in the registry record. Their absence limits evaluation of statistical precision and the evidential status of any outcome beyond the descriptive counts.

For clinical researchers, the central statistical lesson is that design and endpoint context govern what can be concluded. These results can be read as safety descriptions in the stated groups. They should not be recast as comparative treatment effects or as evidence of efficacy without an appropriate analysis and supporting 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.

Several limitations specific to this record constrain interpretation. Allocation is nonrandomized, masking is listed as none, and no randomized comparator is reported. Participants and treatment groups may differ in disease status, regimen, or other characteristics, so comparisons across groups would be vulnerable to confounding. The arms also represent distinct study parts rather than parallel alternatives in a controlled treatment comparison.

The phase 1 groups listed in the safety results have six participants at risk each. Counts from groups of this size provide limited information about uncommon events and can change substantially with individual outcomes. The phase 2, part 4 group is larger, with 42 participants at risk, but it remains an uncontrolled group and cannot establish comparative safety or efficacy.

The primary outcome is specified for phase 1, parts 1 and 2, while other outcomes cover additional parts. This difference in scope makes it important not to assume that the primary safety endpoint applies identically to every group or that every outcome uses the same analysis population. The registry record does not report complete outcome results for the listed secondary measures.

Further details are not reported in the registry record, including the statistical analysis plan, missing-data methods, multiplicity handling, interim analyses, reasons for the enrollment target, and full analysis populations for secondary outcomes. The posted serious-event percentages have no stated denominator in the listed information, and event-term overlap is not described. The death counts are not accompanied by treatment-attribution information. These limits do not invalidate the descriptive counts, but they restrict the conclusions that can be drawn from them.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL) — NCT04661007.
• Registry record last updated 2026-10-21; status last verified 2026-09.
• Results first posted 2026-10-21.
• 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

NCT04661007 is an open-label, multicenter phase 1b/2 study of tafasitamab alone or in combinations in Japanese participants with non-Hodgkin lymphoma, including diffuse large B-cell lymphoma. The registry lists nonrandomized allocation, no masking, a parallel model, enrollment of 72, and active, not recruiting status. The listed start date is 2020-12-15, and the primary completion date is 2025-07-01.

The registry’s primary outcome is the number of participants with any treatment-emergent adverse event in phase 1, parts 1 and 2, with a timeframe of up to 1066 days. The safety population includes participants who received at least one dose. Posted adverse-event results list 12 participants with serious adverse events, 70 with other adverse events, and 8 deaths in the total row. These are descriptive counts from nonrandomized groups, not comparative treatment effects.

Secondary outcomes include tafasitamab concentrations, response assessments, lesion reduction, complete response, and duration of response. Detailed statistical methods, missing-data handling, multiplicity procedures, and causal attribution for deaths are not reported in the registry record.