A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL) (NCT05144009), a non-randomized phase 2 study. The primary outcome is CR Rate.

2. Clinical Question

3. Trial Design

LOTIS-9 is described as a phase 2, open-label study of loncastuximab tesirine plus rituximab in previously untreated unfit or frail participants with diffuse large B-cell lymphoma. The registry lists an enrollment of 41 and identifies the study as terminated. The recorded start date is 2022-06-21 and the primary completion date is 2024-01-22. The reason for termination is not reported in the registry record.

The study used a sequential model and non-randomized allocation, with no masking. Cohort A is described as participants who were unfit according to sGA. Cohort B is described as participants who were frail according to sGA or had cardiac comorbidities. Both cohorts received Lonca-R; there is no untreated or alternative-treatment control group in the record. Consequently, the cohort labels do not create a randomized comparison of treatment strategies.

The registry describes an initial course of three cycles in both cohorts. Participants achieving complete response were to receive one additional cycle, while those achieving partial response were to receive three additional cycles. The Cohort B description states a total of up to six cycles. Further administration details are not fully available in the registry record.

Alongside the primary complete-response rate, listed outcomes include overall response rate, progression-free survival at 2 years, overall survival at 3 years, duration of response, treatment-emergent adverse events, and pharmacokinetic measures. The record lists 13 outcome measures, but does not report analysis results for them in the material described by this 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: All-Treated Population: All participants who received at least 1 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: All-Treated Population: all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as CR Rate, measured over Up to a maximum of 17.1 months.

The primary endpoint is the percentage of participants with a best overall response of complete response, determined by the investigator according to the 2014 Lugano Classification criteria. The stated population is all treated participants: those who received at least one dose of study drug. The assessment timeframe is up to a maximum of 17.1 months.

The endpoint definition allows complete response to be based on complete metabolic response on PET-computed tomography, or on complete radiologic response on CT when disease was not FDG-avid at baseline. For the CT definition, the record specifies target node regression to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions, and normal bone marrow morphology.

In general, a response endpoint expresses how many participants meet a defined disease-response criterion over a specified assessment period. Complete response is a categorical outcome under the stated criteria, rather than a direct measure of how long a response lasts. Duration of response is separately listed as a secondary outcome. The endpoint definition is reported, but its observed rate and confidence interval are not reported in the registry record. Without those results, the endpoint cannot quantify the observed response frequency or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary percentage endpoint: each participant either meets the complete-response definition or does not. The posted primary endpoint is the percentage of participants whose best overall response was complete response. Although the record identifies a 95% confidence interval as the dispersion measure, neither the estimate nor its interval is reported in the registry record.

What does a confidence interval convey?

General explanation: a confidence interval expresses statistical uncertainty around an estimate. For a percentage, the interval reflects that the observed participants are one sample from a broader population of interest. Its width depends on features such as the number of observations and the observed proportion, as well as the interval method. An interval is not a guarantee that the true value lies within its limits, and it does not account automatically for limitations such as non-randomized cohort assignment or incomplete outcome data. Because the primary estimate and interval are not reported, their width and the resulting degree of precision cannot be assessed.

Why does the analysis population matter?

The primary population is defined as all treated participants, meaning those who received at least one dose of study drug. This is not automatically the same as all enrolled participants: the registry definition explicitly starts with treatment received. The record does not report the number analyzed for the primary endpoint or explain how participants without an evaluable response were handled. Those details matter because the denominator determines the interpretation of a percentage. An analysis limited to participants with an observed response could differ from one that applies a specified missing-outcome rule.

What can the cohort structure tell us?

The study is non-randomized, open-label, and sequential. Both cohorts received Lonca-R, while the cohorts were defined using unfit, frail, or cardiac-comorbidity descriptions. General explanation: random allocation helps balance measured and unmeasured participant characteristics between treatment groups, on average. Without randomization and a separate control group, an observed outcome cannot by itself distinguish the contribution of treatment from participant characteristics, study context, or other factors. Open-label status means masking was absent; the record does not describe additional protections against assessment bias. The response outcome was determined by the investigator, so lack of masking is relevant to interpretation, though the record does not quantify any such influence.

How should planning calculations be read?

The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. For time-to-event outcomes, the illustrations concern total events; for other outcomes, they concern participants per arm. These are planning assumptions, not outcomes from the trial and not evidence of achieved power. No calculated sample-size values or underlying observed effect are reported in the registry record. The record also does not report the trial's own sample-size justification, so these illustrations should not be mistaken for its original design rationale.

What analysis details remain unknown?

The registry record reports no analyses. It does not report the method used to construct the confidence interval, any adjustment or stratification, an interim-analysis plan, a statistical analysis plan, or a method for handling missing outcomes. These are distinct from the endpoint definition: knowing what counts as complete response does not specify how all enrolled or treated participants were included in the final analysis. General explanation: analysis choices can affect estimates and uncertainty, particularly when data are missing or when multiple outcomes are examined. Without the relevant methods and results, readers cannot reproduce the primary analysis or evaluate its sensitivity to alternative assumptions.

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("Cohort A: Loncastuximab Tesirine + Rituximab (Lonc", "Cohort B: Loncastuximab Tesirine + Rituximab (Lonc")
n      <- c(17, 24)
events <- c(9, 10)
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  Cohort A: Loncastuximab Tesirine + Rituximab (Lonc  17  9  52.9  27.8  77.0  31.0  73.8  30.8  74.0
ARM  Cohort B: Loncastuximab Tesirine + Rituximab (Lonc  24  10  41.7  22.1  63.4  24.5  61.2  24.4  61.3

11. Multiplicity, Missing Data and Analysis Populations

The record lists 13 outcome measures, including the primary complete-response rate and secondary measures of response, survival, duration of response, treatment-emergent adverse events, and pharmacokinetics. It does not report a multiplicity strategy, such as a prespecified ordering of tests or an adjustment for examining multiple outcomes. The statistical plan is not reported in the registry record. This means it is not possible to determine from the record how the investigators intended to control the chance of false-positive findings across multiple statistical tests, if such testing was planned.

The registry identifies the primary population as all treated participants, defined as participants who received at least one dose of study drug. It does not report the number included in the primary analysis, the number with missing response assessments, or the treatment of participants whose response status was unavailable. A missing-data method is not reported in the registry record. The record also does not describe analysis populations for the secondary outcomes.

General explanation: missing outcome data can affect a percentage if participants with unavailable results are excluded or classified under an assumed outcome. The impact depends on how much data are missing and why they are missing; neither is described for the primary endpoint in the registry record. A clear analysis population and missing-data rule are therefore necessary for judging how a reported response percentage relates to all participants who started treatment. No such primary analysis details or numerical results are reported.

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: pleural effusion (29.4%), pneumonia (20.8%), pericardial effusion (11.8%), cardiac failure (11.8%), sepsis (11.8%).

The registry lists serious adverse event counts by cohort. In Cohort A, 13 of 17 participants at risk were recorded as affected by a serious adverse event; in Cohort B, 16 of 24 participants at risk were recorded as affected. The other adverse-event fields list 17 of 17 participants at risk in Cohort A and 22 of 24 in Cohort B as affected. These figures describe the counts recorded in the registry; they do not establish that an event was caused by Lonca-R.

The serious-event terms listed include pleural effusion (29.4%), pneumonia (20.8%), pericardial effusion (11.8%), cardiac failure (11.8%), sepsis (11.8%), and acute respiratory failure (11.8%). The denominator and event-count basis for these term percentages are not reported in the registry record. A participant may have experienced more than one event, so event terms should not be read as mutually exclusive categories or added together.

The registry also records 5 deaths in Cohort A and 10 in Cohort B. The record does not report the causes, timing, or relationship of these deaths to treatment. Since the cohorts were not randomized and differ in their defining participant characteristics, their safety counts are not a controlled comparison. The reason for termination is not reported in the registry record.

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

The record specifies a clinical question: the complete-response percentage among treated participants with previously untreated diffuse large B-cell lymphoma who were considered unfit or frail, or had cardiac comorbidities, in a study of Lonca-R. It also defines the response criteria and the maximum primary-endpoint timeframe. Those details clarify what outcome the study was designed to assess.

However, the primary result is not reported in the registry record. There is no observed complete-response percentage, participant count with complete response, or confidence interval to interpret. The record therefore cannot show the frequency of complete response in the analyzed population or the precision of that estimate. The listed secondary outcomes likewise do not have results reported in the registry record.

The study design does not provide a randomized comparator. Both cohorts received Lonca-R, and allocation was non-randomized. Any difference between cohort outcomes would not, on its own, show that treatment caused the difference, because the cohorts were defined by participant characteristics rather than randomized assignment. The record provides no basis for comparing Lonca-R with another treatment or with no treatment.

General explanation: a trial outcome is most informative when its estimate, uncertainty, population, analysis rules, and comparator are all clear. Here, the population and endpoint definition are described, but key results and analysis details are not reported. The record's terminated status is also factual, but its reason is not reported in the registry record. It should not be interpreted as evidence for or against an efficacy or safety conclusion.

Accordingly, the registry record supports a description of the study design and planned measurements, alongside a limited account of recorded safety counts. It does not support a conclusion about whether the combination changes outcomes relative to another approach, nor a definitive statement about the benefit or harm of treatment. Such claims would require results and methods not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and outcome results must be read together. The registry gives a detailed definition of complete response, including PET-computed tomography criteria and an alternative CT definition for disease that was not FDG-avid at baseline. It also specifies the all-treated population and a maximum timeframe of 17.1 months. Those definitions make the intended measurement understandable, but they do not supply the observed estimate or its uncertainty.

The trial also highlights the importance of design when interpreting comparisons. Cohort A and Cohort B both received Lonca-R, but cohort assignment was non-randomized and based on participant descriptions. The cohorts therefore do not function as a randomized control comparison. This distinction matters even when numerical results are available: a difference between groups may reflect differences in who entered each cohort rather than treatment effects.

General statistical explanation: precision and causal interpretation are separate questions. A confidence interval can describe uncertainty around an estimate, while randomization and an appropriate comparator address a different issue: whether an observed contrast can be attributed to the treatment. In this record, the primary estimate and interval are not reported, and the design has no randomized control group.

The record further shows why registration details about analysis populations, missing outcomes, multiplicity, and termination can matter. The endpoint population is defined, but analysis counts and missing-data methods are not reported. The study is listed as terminated, but the reason is not reported. These omissions limit how fully the study's results and conduct can be evaluated from the registry record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations specific to this trial record constrain interpretation. First, the registry does not report the primary complete-response estimate, its confidence interval, or the number of participants who achieved complete response. The primary endpoint is therefore defined but not numerically interpretable from the record.

Second, the study was non-randomized, open-label, and had no control arm. Both cohorts received Lonca-R, and the cohort definitions differ: Cohort A is described as unfit according to sGA, while Cohort B is described as frail according to sGA or as having cardiac comorbidities. A direct comparison between cohorts would not be a randomized treatment comparison.

Third, the record reports no analyses and does not report the primary analysis count, a missing-data method, the statistical analysis plan, or a multiplicity approach. The registry does not explain the termination, and the reason is not reported in the registry record. It also does not provide the denominator basis for the listed serious-event term percentages.

The listed enrollment is 41, but the record does not provide a primary analysis count that would show how many participants contributed to the complete-response estimate. The primary population definition requires receipt of at least one dose, and enrollment alone does not establish how many participants met that definition. No inference about why participants may be absent from an analysis can be made from this record.

These are limitations of the information available in the registry record and of the described design. They do not establish that a particular result is biased or that an unreported analysis was not performed; they mean that those details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL) — NCT05144009.
• Registry record last updated 2025-01-30; status last verified 2025-01.
• Results first posted 2025-01-30.
• 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

LOTIS-9 is a phase 2, open-label, non-randomized, sequential study of loncastuximab tesirine plus rituximab in previously untreated unfit or frail participants with diffuse large B-cell lymphoma. The registry lists enrollment of 41 and status as terminated. Cohort A is described as unfit according to sGA; Cohort B is described as frail according to sGA or as having cardiac comorbidities.

The primary endpoint is complete-response rate among participants who received at least one dose, assessed by investigator determination using the 2014 Lugano Classification criteria, up to a maximum of 17.1 months. The primary result and its confidence interval are not reported in the registry record. The record lists 13 outcome measures and no analyses. It does not report the reason for termination, a missing-data method, or the statistical analysis plan.