Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL) (NCT02669017), a non-randomized phase 1 study. The primary outcome is Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This was a Phase 1 study of ADCT-402 in participants with relapsed or refractory B-cell lineage non-Hodgkin lymphoma. The registry records 183 participants enrolled and identifies the study as completed. It lists a start date of 2016-03 and a primary completion date of 2019-02-21.

The trial had two parts. Part 1 used dose escalation, with intravenous ADCT-402 administered on Day 1 of each cycle. The registry describes escalation from 15 µg/kg to 200 µg/kg under a 3+3 study design. Cycle lengths were 3 or 6 weeks. Part 2 was a dose-expansion phase: participants received dose level or levels and schedules identified in Part 1 by the Dose Escalation Steering Committee. The listed Part 2 doses were 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle.

Allocation was non-randomized, masking was absent, and the model was single-group. Thus, the dose cohorts reflect the study’s escalation and expansion structure rather than randomized treatment groups. Comparisons across dose cohorts can be descriptive, but differences between them cannot be attributed to dose alone from this design. Cohorts may differ for reasons not resolved by the registry information.

The registry lists overall response rate, duration of response, overall survival, progression-free survival, and pharmacokinetic measures among secondary outcomes. Numerical results for those endpoints are not reported in the registry record. The record also does not report the detailed statistical analysis plan, dose-escalation decision rules beyond the stated 3+3 design, or the rationale for the enrollment target.

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: Participants were screened at 11 sites in 3 countries.

Only the first 6 of 9 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants in Part 1 who completed at least one cycle 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 participants who received at least one dose of study treatment.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs), measured over Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks).

The primary endpoint is the number of Part 1 participants who experienced dose-limiting toxicities, or DLTs. The registry defines the endpoint as a count of participants, not as a continuous measurement or a time-to-event estimate. Its stated population includes Part 1 participants who completed at least one cycle of treatment.

The observation window covers Cycle 1: Day 1 to the end of Cycle 1, which is 3 weeks for the Q3W schedule and 6 weeks for the Q6W schedule. A DLT is a prespecified safety event, with hematologic and non-hematologic criteria. Examples include certain severe or prolonged blood-count toxicities, severe tumor lysis syndrome, qualifying Grade 3 or higher non-hematologic adverse events, and Grade 2 or higher skin ulceration. Events clearly due to underlying disease or extraneous causes are excluded by the definition.

In general, a DLT endpoint is used in early-phase dose escalation to characterize treatment-limiting toxicity over a defined observation period. It can inform decisions about which doses merit further evaluation. It does not by itself establish comparative safety, long-term tolerability, or antitumor benefit. The registry record does not report how many participants met the DLT definition, so the primary endpoint cannot be interpreted numerically from the available record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The design and endpoint determine which statistical interpretations are appropriate. This study was a non-randomized, unmasked, single-group Phase 1 trial with dose escalation followed by dose expansion. Its primary measure was a participant count for dose-limiting toxicities during Cycle 1, rather than a comparative estimate against a control group.

What does a participant count represent?

A count records how many participants in a defined population experienced an event. The population and event definition matter: the primary endpoint applies to Part 1 participants who completed at least one cycle, and a DLT must meet the protocol’s specified criteria within the Cycle 1 window. It is not appropriate to replace that endpoint with a broader count of all adverse events or all serious adverse events. The registry record does not report the primary count or an endpoint estimate.

Counts are often accompanied by a denominator so readers can understand the group to which the count refers. In the safety information, each cohort is described with an at-risk count and an affected count for serious and other adverse events. These are descriptive cohort summaries. Without a control arm and a defined comparative analysis, they do not estimate a treatment difference. The registry record does not state the statistical method used to analyze the safety summaries.

Why does dose escalation matter?

In general, dose-escalation studies examine safety as dose levels increase and use observed tolerability to guide further evaluation. The registry identifies a 3+3 design for Part 1, but it does not report the detailed implementation of escalation decisions or the full protocol rules. The design description alone does not reveal how many participants were evaluable at each decision point, whether any replacements occurred, or how each escalation decision was made.

Part 2 expanded evaluation at dose level or levels selected in Part 1. Its purpose and position in the study differ from Part 1’s escalation phase. Consequently, an apparent difference between Part 1 and Part 2 counts may reflect differences in cohort composition, study phase, exposure, or other factors, as well as dose. The registry record does not provide an adjusted analysis that would separate these explanations.

What can be inferred without randomization?

In general, random allocation helps balance measured and unmeasured participant characteristics between treatment groups. This trial was non-randomized and had no separate control treatment, so differences across dose cohorts are not protected by that design feature. Cohort-level counts can describe what was observed in the listed groups, but they cannot establish what would have happened to the same participants under another dose or a comparator treatment.

The absence of masking also means treatment assignment was not concealed from participants or study personnel according to the registry. For an objectively defined event count, this does not automatically invalidate observations, but it can matter to event identification, reporting, or assessment. The registry record does not describe procedures used to reduce assessment bias.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate under a statistical model and specified assumptions. It can distinguish a precise estimate from one compatible with a broad range of values. No confidence intervals for the primary endpoint or secondary endpoints are reported in the registry record. Without an estimate and its uncertainty, readers cannot assess statistical precision or use a significance test to evaluate a treatment contrast.

The record lists 18 outcome measures and no analysis entries. It does not report the statistical methods for secondary outcomes, the handling of repeated or multiple outcomes, or whether any planned analyses were adjusted for participant characteristics. These details should not be inferred from the Phase 1 designation or from the listed endpoints.

How should planning calculations be understood?

In general, sample-size planning illustrations answer a hypothetical design question: how many participants might be needed under stated assumptions to detect a chosen effect at a specified power and significance level. Such calculations depend on assumptions about the effect, variability or event rate, allocation, and analysis method. They are planning quantities, not observed results, and they are not “observed power.” The registry record does not report its own sample-size justification or detailed assumptions. Any planning illustration based on an observed effect would also depend on the availability and reliability of that effect estimate; no primary endpoint estimate is reported in this registry record.

For time-to-event outcomes, general methods account for event timing and censoring, while binary outcomes are based on whether an event occurred in a defined period. The registry lists survival and progression-free survival as secondary outcomes, but does not provide their analysis details or numerical results. No model, adjustment strategy, or treatment-effect estimate for those endpoints is reported in the registry record.

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("Part 1: 15 μg/kg Q3W", "Part 1: 30 μg/kg Q3W", "Part 1: 60 μg/kg Q3W", "Part 1: 90 μg/kg Q3W", "Part 1: 120 μg/kg Q3W", "Part 1: 150 μg/kg Q3W")
n      <- c(4, 4, 3, 5, 16, 16)
events <- c(0, 0, 0, 0, 1, 1)
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  Part 1: 15 μg/kg Q3W  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Part 1: 30 μg/kg Q3W  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  Part 1: 60 μg/kg Q3W  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  Part 1: 90 μg/kg Q3W  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Part 1: 120 μg/kg Q3W  16  1  6.2  0.2  30.2  1.1  28.3  1.5  28.7
ARM  Part 1: 150 μg/kg Q3W  16  1  6.2  0.2  30.2  1.1  28.3  1.5  28.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes: response rate, duration of response, overall survival, progression-free survival, and pharmacokinetic measures including concentration, time to maximum concentration, and area-under-the-curve measures. It also records 18 outcome measures in total. When many outcomes are considered, the chance of at least one apparently notable result can increase. In general, prespecified testing hierarchies or multiplicity adjustments can address that issue, but the registry record does not report whether such procedures were planned or used.

The registry does not report how missing endpoint observations were handled, whether participants who did not complete Cycle 1 were included in any analysis, or how the analysis population was defined beyond the primary endpoint’s stated population. It also does not report how incomplete follow-up, treatment discontinuation, or unavailable outcome assessments were addressed. These omissions prevent assessment of whether missingness could affect the results.

The primary endpoint population is specified as Part 1 participants who completed at least one treatment cycle. That definition does not establish how all enrolled participants were treated analytically or whether a separate safety population was used. The registry record does not report an analysis plan, missing-data methods, or sensitivity analyses. No analysis entries are listed, so there are no reported estimates from which to judge the effect of those choices.

In general, missing-data methods rely on assumptions about why observations are missing. Those assumptions can materially affect interpretation, especially when the endpoint is safety-related or follow-up differs between participants. The registry information is insufficient to determine which assumptions or methods, if any, were applied.

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: cardiac arrest (25.0%), muscular weakness (25.0%), febrile neutropenia (20.0%), neutropenia (20.0%), abdominal distension (20.0%).

The serious adverse-event figures are cohort-specific counts of affected participants among those listed as at risk. They are not DLT counts and should not be read as comparative treatment effects. The registry lists 1 of 4 in Part 1 at 15 μg/kg Q3W; 1 of 4 at 30 μg/kg Q3W; 0 of 4 at 60 μg/kg Q3W; 4 of 5 at 90 μg/kg Q3W; 4 of 16 at 120 μg/kg Q3W; 4 of 26 in Part 2 at 120 μg/kg Q3W; 6 of 19 at 150 μg/kg Q3W; 40 of 69 in Part 2 at 150 μg/kg Q3W; and 15 of 36 at 200 μg/kg Q3W and Q6W.

The record also lists deaths by cohort, but does not report causal attribution. A death count during a trial is not equivalent to a count of deaths caused by treatment. The listed serious-event terms include cardiac arrest and muscular weakness, each reported as 25.0%, and febrile neutropenia, neutropenia, abdominal distension, and fatigue, each reported as 20.0%. The registry information does not give the context needed to interpret these term percentages as comparative risks.

Because the study was non-randomized and had no control group, variation across cohorts should be interpreted descriptively. Exposure, follow-up, dose, and cohort membership may differ, and the registry record does not provide an adjusted comparison.

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

The registry record establishes that a Phase 1 study evaluated ADCT-402 through dose escalation and dose expansion in participants with relapsed or refractory B-cell lineage non-Hodgkin lymphoma. It defines a primary safety endpoint based on dose-limiting toxicities during Cycle 1 and reports cohort-level serious adverse-event information. It does not report the numerical result for the primary endpoint.

The record also lists secondary outcomes related to response, survival, and pharmacokinetics, but does not report numerical results for them. Therefore, the posted information does not establish the observed response rate, duration of response, overall survival, progression-free survival, or pharmacokinetic estimates. It also does not provide confidence intervals or statistical tests for these endpoints.

Serious adverse-event counts and death counts are important descriptive safety information, but they do not by themselves show that treatment caused an event or that one dose is safer than another. The cohorts were not randomized comparisons, and no control treatment was included. Differences between cohorts may reflect factors other than dose, and the registry record does not report an adjusted analysis that addresses those differences.

In general, a Phase 1 dose-escalation study is designed to characterize early safety and inform further evaluation; it is not, by itself, a controlled test of efficacy. The record’s stated design and endpoints should therefore be distinguished from claims about clinical benefit. No conclusion that ADCT-402 does or does not work follows from the information reported in this registry record.

The record also does not report its detailed statistical analysis plan, missing-data methods, multiplicity procedures, or sample-size justification. Those omissions limit assessment of how endpoint results would have been analyzed and how precise any estimates might be.

14. Why This Trial Matters Statistically

This study illustrates why the design and endpoint definition are central to interpreting early-phase clinical data. Its primary endpoint is a count of participants meeting a prespecified DLT definition during the first cycle, with the observation period differing for Q3W and Q6W schedules. That is a focused early safety question, not a direct estimate of comparative benefit.

The two-part structure also matters. Part 1 escalated dose levels under a stated 3+3 design; Part 2 expanded evaluation at dose levels and schedules selected after Part 1. Keeping those phases distinct helps prevent an expansion cohort from being treated as though it were a randomized control or a direct replica of the escalation cohorts.

The registry reports serious adverse-event counts across dose cohorts, while the primary DLT result and numerical secondary endpoint results are not reported. This contrast highlights an important statistical distinction: event summaries can be informative descriptively even when they do not answer the primary endpoint or support a treatment-effect estimate. A safety count, a DLT count, and an efficacy outcome are not interchangeable measures.

The non-randomized, single-group design also limits causal interpretation. In general, randomized control groups help establish a basis for attributing differences to treatment. Without such a comparison, observed variation across cohorts cannot isolate the effect of dose from other differences between participants or study phases.

Finally, the record shows why reporting analysis methods and uncertainty matters. Without endpoint estimates, confidence intervals, missing-data methods, and the statistical plan, readers cannot assess precision or determine how conclusions account for multiple outcomes. The design can be described from the registry, but the available record does not support a complete statistical appraisal of the trial’s outcomes.

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 primary limitation for interpreting the trial statistically is that the registry record does not report the primary DLT count or numerical results for the listed secondary outcomes. It is therefore not possible to describe endpoint estimates, their precision, or statistical significance from this record.

The study was non-randomized, unmasked, and single-group, with dose escalation followed by expansion. As a result, comparisons across its cohorts are not like-for-like control comparisons. Dose, study phase, schedule, and participant composition may vary together, and the registry does not report an adjusted analysis to address those factors.

The primary endpoint population is limited to Part 1 participants who completed at least one cycle. The record does not explain how participants who did not meet that criterion were handled in the analysis, or how missing observations and incomplete follow-up were addressed. The full statistical analysis plan, multiplicity procedures, and sample-size justification are also not reported in the registry record.

Serious adverse-event and death counts are reported by cohort, but the record does not provide causal attribution for deaths or a controlled estimate of comparative risk. The listed serious-event term percentages lack enough context in the registry information to serve as comparative estimates. These safety summaries should be interpreted as descriptive rather than causal.

Although a 3+3 design is stated for Part 1, the registry record does not provide full dose-escalation rules or decision details. The reported information is therefore insufficient to reconstruct the study’s dose decisions or evaluate the operating characteristics of the design.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL) — NCT02669017.
• Registry record last updated 2021-05-19; status last verified 2021-04.
• Results first posted 2020-04-13.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry identifies a completed Phase 1 study of ADCT-402 in participants with relapsed or refractory B-cell lineage non-Hodgkin lymphoma. It records 183 participants enrolled and describes a non-randomized, unmasked, single-group study with dose-escalation and dose-expansion parts. Part 1 used a 3+3 design, and Part 2 evaluated dose levels selected after Part 1.

The primary endpoint was the number of Part 1 participants who experienced DLTs during Cycle 1. The registry record does not report that endpoint’s numerical result. It lists secondary response, survival, and pharmacokinetic outcomes without numerical results, and includes cohort-level serious adverse-event counts and deaths. The record does not report inferential analysis entries, detailed statistical methods, missing-data handling, multiplicity procedures, or the sample-size justification. Because there was no randomized control group, cohort-level safety counts are descriptive and do not support direct causal comparisons between doses.