Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (NCT03589469), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

The study is identified as LOTIS-2 and is a Phase 2 evaluation of efficacy and safety. Its stated clinical focus is disease that is recurrent or refractory. The response endpoint summarizes whether a participant achieved either of the two specified response categories during the assessment period; it is not a direct comparison of treatment effects between groups.

The primary endpoint timeframe is up to 21.5 months. The registry describes the primary analysis population as all-treated participants, meaning those who received at least 1 dose. It does not report how many participants met that definition or the number whose response could be evaluated. The listed enrollment is 145, but enrollment alone does not establish the size of the primary endpoint population.

3. Trial Design

This completed Phase 2 study is described as open-label and single-arm. It lists enrollment of 145 and evaluates loncastuximab tesirine in participants with relapsed or refractory DLBCL. Because there is only one treatment group, the study can describe outcomes observed among participants receiving the study treatment, but it cannot directly estimate a randomized difference against a concurrent control group.

The treatment is administered by intravenous infusion over 30 minutes on Day 1 of each cycle, with cycles every 3 weeks. The listed regimen begins with 150 μg/kg for 2 cycles and then changes to 75 μg/kg for subsequent cycles. Treatment may continue for up to one year, subject to disease progression, unacceptable toxicity, or another reason for discontinuation. The registry does not report how many participants received each number of cycles or how long participants remained on treatment.

The primary outcome is overall response rate, assessed by central review according to the 2014 Lugano classification. The outcome is defined as the percentage of participants whose best overall response was complete response or partial response. Its stated timeframe is up to 21.5 months. Other listed outcomes include duration of response, complete response rate, relapse-free survival, progression-free survival, overall survival, treatment-emergent adverse events, and clinically significant changes in laboratory tests and vital signs.

The registry lists a start date of 2018-08-01, a primary completion date of 2020-05-24, and a completed status. It does not report a separate control group, allocation between groups, or masking; the study is explicitly identified as having no masking. Details such as eligibility criteria, site structure, and the schedule of response assessments 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: All-treated population - all participants who received at least 1 dose of treatment.

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 treatment.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR), measured over Up to 21.5 months.

Overall response rate (ORR) is the percentage of participants whose best overall response during the specified assessment period is complete response or partial response. Here, the response is determined by central review using the 2014 Lugano classification, and the stated timeframe is up to 21.5 months. The analysis population is defined as all-treated participants: everyone who received at least 1 dose.

As a binary endpoint, each participant contributes to one of two broad outcome categories for this measure: meeting the response definition or not meeting it. ORR therefore gives a concise summary of the share of the defined population reaching either response category. It does not, by itself, describe how long a response lasts, how quickly it occurs, or what happens after treatment ends. Duration of response and several time-to-event outcomes are listed separately among the secondary outcomes.

Central review is part of the endpoint definition in this study. In general, using a specified review process helps make the response assessment consistent with the stated classification criteria. The registry does not report further details about the review procedures or how disagreements were handled.

The registry record does not report the observed ORR, the number of participants counted as responders, the denominator used in the calculation, or the 95% confidence interval. Without those results, the endpoint definition can be described, but the size and precision of the observed response estimate cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies ORR as the primary endpoint and describes it as a percentage of participants. It defines a responder as a participant whose best overall response is complete response or partial response, with response determined by central review according to the 2014 Lugano classification. The named population consists of participants who received at least 1 dose. These details identify what the endpoint is intended to summarize, but they do not give the observed result or the precise analysis procedures.

What does a percentage endpoint summarize?

General statistical explanation: a percentage for a binary endpoint is formed by counting participants who meet a defined outcome and relating that count to the number of participants included in the analysis. In this study, the endpoint definition identifies which response categories count. The registry record does not report the responder count or the endpoint denominator, so the posted information does not permit the estimate to be reconstructed or checked.

A percentage is a point estimate: it gives one summary of the observed data. By itself, it does not show how much uncertainty surrounds that estimate. The registry identifies a 95% confidence interval as the measure of dispersion for ORR, but the interval limits are not reported. General statistical explanation: a confidence interval is a range calculated by a specified method to represent uncertainty in an estimate. Its interpretation depends on the method and assumptions used; those calculation details are not reported.

Why does the analysis population matter?

The primary population is defined as all-treated participants, meaning participants who received at least 1 dose. This definition is important because the population used in the calculation determines which participants contribute to the estimate. The listed enrollment is 145, but the record does not state the count in the all-treated population, whether every enrolled participant received treatment, or how participants without an assessable response were handled. It would therefore be inappropriate to assume that enrollment is the exact ORR denominator.

General statistical explanation: when outcome data are missing, the way those participants are treated in an analysis can affect both the estimate and its uncertainty. Common approaches rely on different assumptions about missingness and outcomes. The registry record does not describe an approach, so no particular method should be attributed to this study.

What follows from a single-arm design?

This study has one treatment group and no randomized comparator. A single-group summary can describe outcomes observed in that group, but it cannot estimate a treatment-versus-control contrast from randomized groups. General statistical explanation: random allocation supports comparability between groups, on average, by reducing the influence of factors that might otherwise differ between them. That comparison is not available in this design. The record does not state a historical or external control analysis, and none should be inferred.

The design is also open-label. The primary outcome is based on central review, but the registry does not report operational details that would establish how review was conducted or whether reviewers were unaware of other information. The study’s masking status is listed as none; this should not be confused with unreported details of the central review process.

What is known about the statistical plan?

The registry lists no analyses. It names the primary endpoint and its confidence-interval measure, but does not report the statistical analysis plan, the interval calculation method, any hypothesis test, or a decision threshold for the primary endpoint. The planned number of participants and the justification for that number are not reported in the registry record. The listed enrollment of 145 is not, by itself, evidence of how the sample size was selected or of the precision anticipated by the investigators.

The record includes general assumptions for a sample-size planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect described as a fraction of an observed effect. Those assumptions describe a planning illustration, not the design of this single-arm study. The record says that time-to-event illustrations use a total event count and other illustrations use participants per arm. It does not report the resulting planning values. Such illustrations are not observed power and do not establish the trial’s original design justification.

General statistical explanation: power is a design quantity tied to a specified effect, variability, analysis method, and sample size. Calculating power after observing results does not establish how likely the study was to detect a real effect before the study began. Planning illustrations based on an observed effect are especially dependent on that observed estimate and should not be interpreted as an independent measure of evidential strength.

How should multiplicity and secondary outcomes be viewed?

The registry lists several secondary outcomes, including duration of response, complete response rate, relapse-free survival, progression-free survival, overall survival, treatment-emergent adverse events, and laboratory and vital-sign changes. It does not report how these outcomes were ordered for testing, whether formal hypothesis tests were planned, or how multiplicity was addressed. General statistical explanation: examining multiple outcomes can increase the chance of at least one apparently notable result when each is assessed separately. A prespecified strategy may control or otherwise describe that issue, but no such strategy is reported.

Overall, the endpoint definition is available, while the numerical result and important analysis details are not. The record supports a description of the intended measure and study structure, not a reconstruction of the statistical analysis.

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("Loncastuximab Tesirine")
n      <- c(145)
events <- c(70)
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  Loncastuximab Tesirine  145  70  48.3  39.9  56.7  40.3  56.3  40.3  56.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 21 outcome measures, including the primary ORR endpoint and several secondary outcomes. The secondary list includes duration of response, complete response rate, relapse-free survival, progression-free survival, overall survival, treatment-emergent adverse events, and clinically significant changes in laboratory tests and vital signs. The registry does not report the statistical plan for these outcomes, how they were prioritized, or whether formal testing was intended.

General statistical explanation: when many outcomes or comparisons are assessed, the chance of finding at least one seemingly notable result can increase. Statistical procedures or a prespecified hierarchy can address multiplicity, but the registry record does not report whether such procedures were used. No adjustment or testing strategy should be assumed.

The primary population is defined as all participants who received at least 1 dose. The record does not report the size of that population, the number with an evaluable response, or how missing response data were handled. It also does not say whether participants who discontinued treatment, had incomplete assessments, or lacked later assessments were included in particular analyses. General statistical explanation: missing-data methods require assumptions about why observations are missing and how those participants’ outcomes relate to observed outcomes. Different assumptions can lead to different estimates; none is specified.

The registry lists no analyses. Thus, it does not provide the statistical procedures, sensitivity analyses, or missing-data analyses used for the primary or secondary outcomes. The absence of these details in the registry entry should be read as unreported information, not as evidence that a particular approach was or was not used elsewhere.

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: hypercalcaemia (4.1%), febrile neutropenia (3.4%), pyrexia (2.8%), abdominal pain (2.1%), pleural effusion (2.1%).

The adverse-event summary lists 145 participants at risk in the loncastuximab tesirine group. It records 57 participants as affected for the serious-event summary and 139 for the other adverse-event summary. It also lists 97 deaths. The registry record does not provide enough detail to interpret the deaths in relation to treatment, timing, cause, or the adverse-event categories; these counts should not be treated as evidence of causation.

The listed serious-event terms and percentages are hypercalcaemia, 4.1%; febrile neutropenia, 3.4%; pyrexia, 2.8%; abdominal pain, 2.1%; pleural effusion, 2.1%; and anaemia, 1.4%. These are entries in the posted safety summary. The record does not describe the observation period or provide further definitions for these term-level percentages in the information.

General statistical explanation: safety counts describe events recorded in the population and observation period used for the summary. They do not, on their own, establish that treatment caused an event, nor do they provide a comparison against background risk or another treatment. A single-arm study cannot make a randomized safety comparison. The counts should be read alongside their definitions and reporting context, some of which are not reported in the registry record.

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

This registry entry describes a Phase 2, open-label, single-arm study of loncastuximab tesirine in participants with relapsed or refractory DLBCL. It identifies the primary endpoint as ORR, defined using complete response or partial response and assessed by central review according to the 2014 Lugano classification. It also describes the treatment schedule and lists safety and other clinical outcomes.

The record does not report the numerical ORR, the number of responders, the denominator used for that endpoint, or the 95% confidence interval. As a result, the posted information does not show how large the observed response estimate was or how precisely it was estimated. It also does not allow a reader to determine from this record whether all enrolled participants entered the primary analysis population.

The single-arm design matters to interpretation. The study does not include a randomized comparator, so it cannot directly show how outcomes differed from those in a concurrent control group. General statistical explanation: an observed outcome in one group may be influenced by participant characteristics, the course of disease, assessment practices, and other factors, in addition to treatment. A one-group result cannot separate those influences through a randomized comparison.

The listed adverse-event counts and term-level percentages describe the safety summary, but they are not randomized comparisons and do not establish that treatment caused the events. The record does not supply the detailed context needed to interpret the listed deaths or the observation periods for all safety summaries.

These limitations do not invalidate the study description; they define what can be concluded from this registry entry. It reports the intended response measure and study structure, but not the primary numerical outcome or key analysis details. Any stronger conclusion about response magnitude, precision, comparative effects, or the reasons for particular safety outcomes would go beyond what is reported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a clearly defined response endpoint can be studied in a single treatment group. The registry states the endpoint population, the response categories that count, the central-review basis, and the classification system. Those elements let readers understand what the primary outcome was intended to measure, even though the numerical result is not reported in the registry record.

The design also illustrates an important distinction between describing outcomes and comparing treatments. In a single-arm study, the treatment group’s outcomes can be summarized, but the design does not create a randomized control group for estimating a treatment contrast. General statistical explanation: a comparison group can help distinguish treatment-associated differences from differences that might arise because the groups have different characteristics or follow different courses. That type of randomized comparison is not part of this study.

The listed all-treated definition is another useful interpretive detail. It shows that the primary population is based on receipt of at least 1 dose, rather than simply the enrollment figure. Since the record does not state the all-treated count or endpoint denominator, the reader cannot assume that the listed enrollment of 145 is the denominator for ORR.

Finally, the entry shows why endpoint definitions and numerical results must be read together. The endpoint and a 95% confidence interval are named, but the estimate and interval are not reported. Without them, the precision and scale of the primary finding cannot be assessed. The record’s limitations are therefore as important statistically as its stated design: it allows a careful account of what was planned and measured, while leaving the primary result and key analytical details unavailable in this entry.

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 principal limitation for interpreting this registry entry is that it does not report the primary ORR estimate, responder count, endpoint denominator, or 95% confidence interval. The endpoint definition is detailed, but the numerical result needed to assess its magnitude and precision is absent. The registry also lists no analyses, so it does not provide analysis outputs for the primary or secondary outcomes.

The single-arm, open-label design has no randomized control group. It can describe outcomes in the treated group but cannot provide a like-for-like randomized comparison. The primary endpoint uses central review, but further review procedures are not reported. Eligibility details, assessment schedules, and the all-treated population count are also not reported in the registry record.

The registry does not describe how missing response assessments were handled, whether sensitivity analyses were performed, or how the listed secondary outcomes were treated in the statistical plan. It also does not report a sample-size justification. The enrollment of 145 should not be taken as evidence of a particular design target or of the precision achieved for the primary endpoint.

For safety, the record lists participant counts, deaths, and selected serious-event terms, but the information does not establish causal relationships or give all event definitions and observation details. These limitations apply to interpreting this registry record; they do not establish what may be reported in other documents.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of Loncastuximab Tesirine in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma — NCT03589469.
• Registry record last updated 2023-08-29; status last verified 2023-08.
• Results first posted 2021-07-29.
• 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

This is the registry entry for a completed Phase 2, open-label, single-arm study of loncastuximab tesirine in relapsed or refractory DLBCL. Enrollment is listed as 145. Treatment is described as an intravenous infusion every 3 weeks, beginning at 150 μg/kg for 2 cycles and then 75 μg/kg for subsequent cycles, for up to one year or until a stated reason for discontinuation.

The primary endpoint is ORR, defined as the percentage of all-treated participants with a best overall response of complete response or partial response, assessed by central review according to the 2014 Lugano classification. The timeframe is up to 21.5 months. The numerical primary result and 95% confidence interval are not reported in the registry record.

The record lists secondary efficacy and safety outcomes, and an adverse-event summary. It does not report analysis outputs, missing-data methods, multiplicity procedures, or a sample-size justification. The single-arm design provides no randomized treatment comparison.