Study of ADCT-301 in Patients With Selected Advanced Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of ADCT-301 in Patients With Selected Advanced Solid Tumors (NCT03621982), a non-randomized phase 1 study. The primary outcome is Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

The central safety question was how many participants experienced treatment-emergent adverse events after receiving ADCT-301, either as monotherapy or in combination with pembrolizumab. The registry defines these events by their timing in relation to study treatment, rather than requiring that investigators judge them to have been caused by treatment. Safety was assessed among participants who received study drug.

The official title describes a Phase 1b, open-label dose-escalation and dose-expansion study. Its stated aims included assessing safety, tolerability, pharmacokinetics, and antitumor activity. The primary endpoint is a safety count, while the listed secondary outcomes include response, duration of response, progression-free survival, overall survival, and pharmacokinetic measures. The registry record does not report analyses for those secondary outcomes.

3. Trial Design

This was a Phase 1 study with non-randomized allocation, no masking, and a sequential model. The official title describes dose escalation followed by dose expansion. In dose escalation, participants received ADCT-301 at escalating doses as monotherapy or in combination with pembrolizumab; the combination expansion is described as using a dose identified during escalation. The registry record does not report the decision rules used to select doses or the full protocol details for each cohort.

The record lists 78 as the enrollment and gives the study status as terminated. It records a start date of 2018-11-09 and a primary completion date of 2022-12-14. The reason for termination is not reported in the registry record. Enrollment is a planned or recorded study-level figure; it does not establish how many participants received each regimen or contributed to every outcome.

The study population covered multiple advanced solid tumor types. Participants received ADCT-301 alone or with pembrolizumab. Treatment was organized in 3-week cycles, with follow-up every 12 weeks for up to 1 year after treatment discontinuation, according to the brief summary. The primary outcome specifies a timeframe of up to 3 years. The difference between the follow-up description and the primary-outcome timeframe is not explained in the registry record.

Because treatment was not randomized and there was no masking, comparisons across dose cohorts are descriptive rather than controlled comparisons. Dose, treatment regimen, tumor type, and other cohort features may differ together. No inference that one regimen is superior to another follows from these group-level safety 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: In part 1, participants were to receive escalating doses of camidanlumab tesirine as monotherapy or escalating doses of camidanlumab tesirine in combination with pembrolizumab, guided by a 3+3 design. The study was terminated prior to enrollment for Part 2 of the study.

Only the first 6 of 14 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set: The Safety analysis set consists of all participants who received 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.

Only the first 6 of 15 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs), measured over Up to 3 years.

The primary endpoint counts participants who experienced treatment-emergent adverse events, or TEAEs. The registry defines an adverse event as an untoward medical occurrence in a participant administered a pharmaceutical product; a causal relationship to treatment is not required. A TEAE is an adverse event that occurs or worsens from the first study-drug dose through 30 days after the last dose, or until the start of a new anticancer therapy, whichever occurs earlier.

The endpoint also includes clinically significant changes from baseline in safety laboratory values, vital signs, 12-lead electrocardiogram findings, and Eastern Cooperative Oncology Group performance status when reported as TEAEs. It is a participant count, not a count of all separate event episodes. A participant with more than one event can still contribute as one participant to a count of participants with an event.

Counting TEAEs is useful in an early-phase study because it describes the number of treated participants with events during a defined safety window. It does not by itself establish whether an event was caused by the drug, how severe every event was, or whether the balance of benefits and harms favors a treatment. The registry identifies the Safety Analysis Set as all participants who received study drug. A numerical result for the primary endpoint is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It names a participant-count safety endpoint and defines the Safety Analysis Set, but does not report a statistical analysis plan, a model for the endpoint, confidence intervals, hypothesis tests, or adjusted estimates. The absence of posted analyses should not be filled in by assumptions about standard Phase 1 methods.

What does a participant count measure?

The primary outcome is a count of participants who experienced at least one TEAE during the specified safety window. As a general statistical concept, a participant-level count answers how many people were affected; it is not the same as counting every event episode. It also differs from a rate that incorporates time at risk. A participant who experiences multiple events may contribute once to a participant count, while an event-level summary could count those events separately. The registry record does not post a primary-endpoint total or explain how multiple events were handled in a numerical analysis.

Why does the study structure matter?

In general, random allocation helps make treatment groups comparable at baseline. This trial is explicitly non-randomized and sequential, so its dose and regimen cohorts cannot be treated as randomized comparisons. Escalation studies explore doses and can have groups assembled at different stages or under different treatment conditions. A contrast between two observed counts is therefore descriptive unless an analysis accounts for relevant differences and supports the intended inference. Such an analysis is not reported in the registry record.

The groups also vary by dose and whether pembrolizumab was combined with ADCT-301. The tumor population spans several cancer types. These features mean that a simple pooled summary could obscure clinically and statistically important variation. The registry record does not report a stratified or adjusted analysis, nor does it explain whether outcomes were pooled across tumor types or treatment cohorts.

What can the planning illustration tell readers?

The planning illustrations use the stated assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They describe participant numbers per arm for non-time-to-event outcomes, with the event total used for time-to-event planning. These are planning illustrations based on fractions of an observed effect; they are not the actual design justification reported by the sponsor, and they are not observed power. The registry record does not report the trial's own sample-size justification.

More generally, planning calculations depend on the assumed effect and variability, the statistical test, the allocation, and the chosen significance level. If a planned effect is smaller than the effect used as a reference, more information is generally needed to detect it with the same design assumptions. That general principle does not imply that the actual study was powered for any particular effect. The planning illustration should not be read as evidence that the trial had adequate power for its primary safety endpoint or for efficacy comparisons.

What is missing from the reported statistical methods?

The registry record does not report a model for the binary safety outcome, confidence intervals, p-values, covariate adjustment, dose-response analysis, or formal comparison among regimens. It also does not describe interim analyses, stopping rules, or how the termination decision was made. Since no primary analysis is posted, precision cannot be assessed from a reported interval, and the stability of the event estimates cannot be evaluated using a stated model.

General statistical interpretation distinguishes lack of a reported analysis from evidence of no effect or no difference. Without an estimate and its uncertainty, the reader cannot determine how compatible the data are with different underlying event frequencies. In this non-randomized design, even a reported unadjusted comparison would require caution because group differences may not be attributable to treatment. The currently reported counts support descriptive reading only.

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("ADCT-301 Monotherapy 20 µg/kg", "ADCT-301 Monotherapy 30 µg/kg", "ADCT-301 Monotherapy 45 µg/kg", "ADCT-301 Monotherapy 60 µg/kg", "ADCT-301 Monotherapy 80 µg/kg", "ADCT-301 Monotherapy 100 µg/kg")
n      <- c(3, 5, 5, 5, 8, 7)
events <- c(3, 5, 5, 5, 8, 7)
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  ADCT-301 Monotherapy 20 µg/kg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  ADCT-301 Monotherapy 30 µg/kg  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  ADCT-301 Monotherapy 45 µg/kg  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  ADCT-301 Monotherapy 60 µg/kg  5  5  100.0  47.8  100.0  56.6  100.0  54.1  99.6
ARM  ADCT-301 Monotherapy 80 µg/kg  8  8  100.0  63.1  100.0  67.6  100.0  66.4  99.7
ARM  ADCT-301 Monotherapy 100 µg/kg  7  7  100.0  59.0  100.0  64.6  100.0  63.1  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including overall response rate, duration of response, progression-free survival, overall survival, and pharmacokinetic measures. It lists 20 outcome measures, but no analyses are reported. A strategy for controlling multiplicity across the primary and secondary outcomes is not reported in the registry record.

As a general statistical concept, testing or estimating many outcomes can increase the chance of finding an apparently notable result by chance, especially when results are selected after inspection. A prespecified hierarchy, adjustment, or clear distinction between confirmatory and exploratory analyses can help readers understand the intended interpretation. The registry record does not report such a strategy, so no claim about multiplicity control is warranted.

Missing-data methods are also not reported. The record identifies the Safety Analysis Set as all participants who received study drug, but does not state how missing safety assessments, incomplete follow-up, treatment discontinuation, or missing efficacy assessments were handled. It does not report the size or composition of analysis populations for the secondary outcomes. The safety-set definition clarifies who is eligible for that set; it does not establish that every participant had complete outcome data.

These omissions limit interpretation of both the primary safety question and the listed secondary questions. Without a reported analysis population for each outcome, missing-data strategy, and multiplicity plan, readers cannot determine whether the posted records represent complete follow-up or how uncertainty was treated. Those details are not reported in the registry record and should not be inferred from the study design alone.

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: thyroiditis (100.0%), pericarditis (33.3%), small intestinal obstruction (33.3%), abdominal distension (33.3%), dehydration (33.3%).

The adverse-event figures are organized by dose cohort and treatment regimen. For each cohort, the record gives the number of participants at risk and affected for serious adverse events and for other adverse events, and it lists deaths. These are participant counts, consistent with the registry's description of outcomes as counts of participants with an event. They should not be read as counts of every separate event episode.

The serious-event terms are accompanied by percentages, including thyroiditis at 100.0% and several other listed terms at 33.3%. The denominator for these percentages is not reported in the registry record. Without that information, the percentages cannot be assumed to represent all participants in a treatment group or all participants in the study.

Seriousness, severity, and treatment causality are distinct concepts. The record's primary TEAE definition does not require a causal relationship, and the posted death counts do not establish that deaths were caused by an adverse event or by study treatment. Cohort sizes, exposure, and follow-up also differ or are not fully described in these figures. Treat the results as descriptive safety reporting, not as a like-for-like risk comparison.

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

The posted results describe a non-randomized early-phase study and provide cohort-level safety counts. The named primary endpoint is a count of participants experiencing TEAEs, but a numerical result for that endpoint is not reported in the registry record. The adverse-event figures still offer descriptive information about serious and other events recorded across dose and regimen cohorts; they do not amount to a controlled estimate of treatment-related risk.

The record does not establish that ADCT-301 alone or in combination with pembrolizumab caused the listed events. The TEAE definition is based on timing and explicitly does not require a causal relationship. Similarly, deaths listed within cohorts do not identify cause or attribution. Those counts should not be interpreted as treatment-related mortality without supporting details.

The study also cannot support a like-for-like comparison between monotherapy and combination therapy. Allocation was non-randomized, cohorts were sequential, and dose levels differed. No adjusted comparison is reported. The listed secondary outcomes include response and survival measures, but numerical results for those outcomes are not reported. The registry record therefore does not support a conclusion about antitumor activity or comparative efficacy.

Absence of a reported result is not evidence that an outcome did not occur, that treatments were equivalent, or that there was no difference. It means the registry record does not present an analysis from which those conclusions could be evaluated. The appropriate reading is narrow: these are descriptive safety observations in treated cohorts, with important limits on causal interpretation, precision, and comparison.

14. Why This Trial Matters Statistically

This study illustrates a central statistical challenge in early-phase research: dose-finding and safety description are not the same task as estimating a comparative treatment effect. Sequential cohorts can provide information about events observed at different doses and regimens, but non-randomized group counts do not isolate treatment effects from other differences between cohorts.

The endpoint definition also matters. TEAEs are identified using a treatment-related time window, while causality is not required. This makes the endpoint useful for broad safety surveillance, but it does not mean every counted event was caused by the study drug. Participant counts, event counts, seriousness, severity, and causality each answer different questions and should not be treated as interchangeable summaries.

The record provides a Safety Analysis Set definition and several cohort-level event counts, yet does not report an analysis of its named primary endpoint. It also lists a wide range of secondary efficacy and pharmacokinetic outcomes without analyses. This makes the distinction between an outcome being named and an outcome being statistically reported especially important. A registry outcome list is not itself evidence of a measured treatment effect.

Finally, planning illustrations should be kept separate from observed findings. Sample-size calculations based on an observed effect and stated assumptions are hypothetical planning exercises; they do not show that a trial was adequately powered or that a result is precise. Transparent reporting of analysis populations, denominators, uncertainty, and analytic choices would be needed for stronger interpretation. In this record, the statistically responsible conclusion is descriptive and limited.

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 most important trial-specific limitation is that allocation was non-randomized and the study used sequential dose cohorts. Thus, differences in observed counts across cohorts cannot be interpreted as causal treatment contrasts. The trial included multiple tumor types and both monotherapy and combination regimens, which further complicates direct comparisons.

The record reports planned enrollment of 78, but does not give a complete account of the number treated in each cohort or the number contributing to each endpoint. The safety set includes participants who received study drug, but the record does not state how incomplete assessments or differing follow-up were handled. The reason the study was terminated is not reported in the registry record.

The primary endpoint is defined, but its numerical result and an uncertainty estimate are not reported. Serious-event percentages are listed without their denominator or calculation basis. The record also does not report the cause or treatment attribution of deaths. These gaps prevent a full assessment of event frequency, precision, and attribution.

Although response and survival outcomes are listed, no analyses are reported for them. Statistical methods, missing-data procedures, multiplicity handling, interim monitoring, and the trial's own sample-size justification are not reported in the registry record. Together, these omissions mean that the available information supports only a cautious descriptive reading of the posted safety figures, not a comparative or causal conclusion.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of ADCT-301 in Patients With Selected Advanced Solid Tumors — NCT03621982.
• Registry record last updated 2024-06-13; status last verified 2024-06.
• Results first posted 2024-06-13.
• 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

NCT03621982 is a Phase 1, open-label, non-randomized study described as dose escalation and dose expansion of ADCT-301, alone or with pembrolizumab, in selected advanced solid tumors. The record lists enrollment of 78, a start date of 2018-11-09, primary completion on 2022-12-14, and status as terminated.

The primary outcome is the number of participants experiencing TEAEs, with a timeframe of up to 3 years. The Safety Analysis Set consists of participants who received study drug. Cohort-level serious and other adverse-event counts and deaths are listed, but the primary endpoint's numerical analysis is not reported. The reason for termination, efficacy analyses, analysis methods, missing-data handling, and multiplicity strategy are not reported in the registry record. Because allocation was non-randomized and sequential, the cohort figures are descriptive rather than controlled comparisons.