A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Patients With Malignant Solid Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Patients With Malignant Solid Tumors (NCT04424641), a na phase 1, phase 2 study. The primary outcome is Number of Participants With Dose Limiting Toxicities (DLTs).

2. Clinical Question

The trial was intended to evaluate the safety of GEN1044, determine a recommended Phase 2 dose, and assess preliminary clinical activity in patients with solid tumors. Its primary question concerned dose-limiting toxicities (DLTs) during the first cycle of treatment. The registry record also lists response and antidrug antibody outcomes, but does not report results for those outcomes.

The study includes Phase 1 and Phase 2 designations, but the registry record does not provide a dose-selection result or explain how the expansion cohorts were analyzed. The listed primary endpoint is a participant count, not a comparative measure of treatment effect. Safety counts can describe events recorded in the dose groups, but without a control group they do not establish what would have occurred under another treatment or without study treatment.

3. Trial Design

This was a first-in-human, open-label trial with dose escalation and expansion cohorts, described in the official title as evaluating the safety of GEN1044 in subjects with malignant solid tumors. The registry lists Phase 1 and Phase 2, sequential allocation, no masking, and an enrollment of 48. Allocation is recorded as not applicable. The sponsor is Genmab.

The trial began on 2020-07-15, and the primary completion date is 2021-10-29. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone does not indicate why the study ended or what conclusions were reached.

GEN1044 is described as an immunoglobulin G1 bispecific antibody targeting CD3 and 5T4. The registry lists dose groups with different dose sequences. Because the study was sequential and no control arm is listed, differences among those groups cannot be treated as randomized comparisons. Their participant counts may also differ, and the registry record does not provide a statistical adjustment or dose-group comparison analysis.

The primary endpoint was the number of participants with DLTs during the first cycle, assessed in a dose-determining set. The record defines that set as participants who received at least one dose during dose escalation and met the minimum exposure criterion with sufficient safety evaluations, or experienced a DLT during the first 21 days. The minimum exposure criterion is not specified in the registry record. The primary endpoint result, dose-selection outcome, and details of any analysis plan are also not reported.

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: A total of 48 participants signed the informed consent form of whom 37 received study drug. The Safety Committee decided to stop enrollment during the dose-escalation part and therefore the expansion part of trial never started. Consequently, results are available for only the dose-escalation part.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Dose-determining set (DDS) included all participants who received at least 1 dose of study drug during the dose-escalation part, and who met the minimum exposure criterion and had sufficient safety evaluations or experienced a DLT during the first 21 days of dosing.

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: Full analysis set included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Dose Limiting Toxicities (DLTs), measured over From Day 1 to Day 21 of first cycle.

The primary endpoint is the number of participants with dose-limiting toxicities from Day 1 to Day 21 of the first cycle. It is a count of participants meeting the registry’s DLT definition, rather than a measure of tumor response or a direct comparison between treatments. DLTs are used in dose-escalation research to identify toxicities considered important for evaluating doses. The registry record does not report the count observed or how that count informed a recommended Phase 2 dose.

The definition includes Grade 3 or higher cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; Grade 3 or 4 hematologic and non-hematologic toxicities, subject to protocol exceptions; and laboratory abnormalities with specified clinical consequences. It also includes Grade 3 or 4 febrile neutropenia, liver toxicity defined by Hy’s law, treatment-related toxicity causing treatment discontinuation during Cycle 1, and any Grade 5 toxicity. The protocol exceptions and the detailed operating rules for applying these criteria are not reported in the registry record.

The endpoint applies to the dose-determining set, not necessarily every enrolled participant. That set is defined by treatment exposure and safety-evaluation criteria, with an alternative inclusion condition for participants who experienced a DLT during the first 21 days. The size of this analysis population and the number meeting the endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants with an event: a participant either meets the DLT definition during the specified assessment period or does not. The count is intended to describe the safety experience in the dose-determining set. To interpret a count as a frequency, the relevant denominator is also needed. The registry record describes how the dose-determining set is defined, but does not report its size or the observed DLT count.

What does a count tell the reader?

A count conveys how many participants met an endpoint, but by itself does not indicate how common the event was among those assessed. A proportion requires both the number meeting the endpoint and the number included in the analysis. In dose escalation, this denominator can differ from overall enrollment because participants may not meet the required exposure or evaluation criteria. The registry record does not give the analysis population size for the primary endpoint.

The DLT endpoint is tied to the first cycle and a set of protocol-defined toxicities. This makes the endpoint dependent on both the assessment window and the rules used to classify events. The registry record gives the timeframe and a broad definition, including toxicity grades and clinical consequences, but does not report all protocol exceptions or adjudication details. General statistical interpretation therefore cannot resolve how borderline or overlapping events were handled.

Why is a sequential dose design different from a randomized comparison?

In general, sequential dose escalation assigns participants as the study progresses through doses according to a dose-escalation approach. The registry record does not specify that approach. A randomized comparison, by contrast, uses random assignment to support comparison between treatment groups. This trial is recorded as sequential, open-label, and without masking, and no control arm is listed. The dose groups are therefore descriptive groups, not randomized controls. Differences in their event counts could reflect differences in participant characteristics, exposure, follow-up, or other factors as well as dose; the record does not provide analyses that separate these possibilities.

The registry lists eight dose sequences: GEN1044 Doses 0.3/3/3 mg, 1/3/10 mg, 1/3/30 mg, 1/5/30 mg, 1/10/30 mg, 1/5/37.5 mg, 1/5/45 mg, and 1/3/60 mg. The presence of these groups does not, by itself, show a dose-response relationship. No formal dose-response estimate or comparison is reported in the registry record.

How should precision and planning be understood?

In general, confidence intervals help express uncertainty around an estimated event frequency or treatment effect. Wider intervals indicate less precision, while narrower intervals indicate greater precision under the analysis assumptions. No confidence intervals or effect estimates for the primary endpoint are reported in the registry record. No p-values or primary outcome analyses are listed either.

Sample-size planning is distinct from observed study results. The planning description attached to the record refers to an illustration based on an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It also distinguishes participants per arm from total events for time-to-event outcomes. Those are planning assumptions, not evidence that this sequential dose-escalation trial used a two-arm randomized design. They are not observed power, and they do not replace a reported sample-size justification. The registry record does not report the protocol’s sample-size justification or the specific analyses behind the planning illustration.

Over-dispersion is a general concern when count data vary more than an assumed statistical model allows; it can make uncertainty estimates too optimistic if ignored. The primary outcome is a count of participants meeting a binary event definition, not a repeated-event count for each participant. The registry record does not report a model for the primary endpoint, so it is not possible to say whether over-dispersion was assessed or whether any model-based inference was used.

Finally, statistical analysis depends on a defined analysis population and transparent handling of incomplete observations. The record defines the dose-determining set conceptually but does not give its size, missing-data methods, or analysis procedures. Without those details and the endpoint result, the posted information supports description of the design, not estimation of the DLT frequency or a comparison of doses.

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("GEN1044 Doses 0.3/3/3 mg", "GEN1044 Doses 1/3/10 mg", "GEN1044 Doses 1/3/30 mg", "GEN1044 Doses 1/5/30 mg", "GEN1044 Doses 1/10/30 mg", "GEN1044 Doses 1/5/45 mg")
n      <- c(1, 4, 4, 3, 2, 3)
events <- c(0, 0, 0, 0, 1, 3)
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  GEN1044 Doses 0.3/3/3 mg  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  GEN1044 Doses 1/3/10 mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  GEN1044 Doses 1/3/30 mg  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  GEN1044 Doses 1/5/30 mg  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  GEN1044 Doses 1/10/30 mg  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6
ARM  GEN1044 Doses 1/5/45 mg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures, including the primary DLT count and secondary outcomes for complete or partial response and antidrug antibodies positive to GEN1044. The record does not report results for the response or antibody outcomes, or any analyses for the listed outcomes. A statistical analysis plan, hierarchy for interpreting outcomes, and multiplicity procedure are not reported in the registry record.

Multiplicity arises in general when several outcomes, treatment comparisons, or repeated statistical tests are assessed. Without a stated analysis plan, readers cannot determine whether testing was planned, how any results would be prioritized, or whether adjustment for multiple testing was used. This matters especially when considering several outcomes together: a nominal finding from one analysis may not have the same interpretation as a prespecified primary analysis. No such statistical findings are posted for this trial.

The primary population is described as the dose-determining set, with eligibility based on receiving study drug during dose escalation and meeting exposure and safety-evaluation criteria, or experiencing a DLT during the first 21 days. The number in that set and its relation to the full enrollment of 48 are not reported in the registry record. The record does not specify how missing or incomplete safety assessments were handled, how participants who discontinued early were analyzed, or whether any imputation was used.

Interim analyses, stopping rules, and any other planned looks at accumulating data are not reported in the registry record. The terminated status does not establish whether a prespecified stopping rule was applied. These omissions limit assessment of how outcomes were selected and how incomplete follow-up may affect the posted summaries.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tumour associated fever (100.0%), diarrhoea (50.0%), cytokine release syndrome (50.0%), pneumonitis (33.3%), vertigo (25.0%).

The safety summary separates serious adverse events from other adverse events and lists participants at risk, participants affected, and deaths for each GEN1044 dose group. For serious adverse events, the listed affected and at-risk counts are 1 and 1 for Doses 0.3/3/3 mg; 1 and 4 for 1/3/10 mg; 3 and 7 for 1/3/30 mg; 5 and 7 for 1/5/30 mg; 4 and 6 for 1/10/30 mg; 1 and 2 for 1/5/37.5 mg; 3 and 4 for 1/5/45 mg; and 5 and 6 for 1/3/60 mg. These are descriptive counts, not adjusted comparisons.

The other-adverse-event counts affected and at risk are 1 and 1, 4 and 4, 7 and 7, 7 and 7, 6 and 6, 2 and 2, 4 and 4, and 5 and 6 across those same dose groups. Death counts are 1, 2, 3, 0, 4, 0, 1, and 2, respectively. The record does not establish that the deaths were caused by treatment, and the counts should not be interpreted as treatment-attributable mortality.

Listed serious-event terms include Tumour Associated Fever at 100.0%, Diarrhoea and Cytokine Release Syndrome at 50.0% each, Pneumonitis at 33.3%, and Vertigo and General Physical Health Deterioration at 25.0% each. These percentages do not by themselves show severity patterns over time or comparative risk. The registry record does not report the underlying denominators for these term percentages or whether participants could contribute to more than one term.

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

The registry record documents a first-in-human, open-label, sequential dose-escalation trial of GEN1044, with a primary safety endpoint focused on DLTs during the first cycle. It also posts group-level adverse-event counts and deaths. These details show what the study set out to assess and provide descriptive safety information by dose group.

The record does not report the primary DLT count or its analysis population size. It also does not report a recommended Phase 2 dose, results for complete or partial response, or antidrug antibody results. Accordingly, the posted information does not establish the frequency of DLTs in the dose-determining set, the precision of that frequency, or whether tumor responses occurred. No statistical result can be inferred from the absence of those outcomes in the record.

The adverse-event counts should not be read as proof that GEN1044 caused an event or a death. The record does not provide a control arm, attribution details for the listed deaths, comparable follow-up information, or adjusted dose comparisons. Different event counts across dose groups do not establish a dose-related pattern, especially in a sequential design where group membership is not randomized.

In general, a trial’s safety observations describe what was recorded among participants who were assessed; they do not by themselves determine what would happen in a different population or under a different treatment. The enrollment of 48 does not identify how many participants contributed to the primary endpoint or each safety summary. The terminated status is part of the record, but its reason is not reported. The conclusions that can be drawn are therefore limited to the study design and the descriptive data posted, not comparative efficacy or a definitive treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a dose-escalation safety objective and a randomized treatment comparison. The registry records sequential allocation, open-label conduct, and no masking, with no control arm listed. These design features make the dose-group counts useful as descriptive summaries of the trial’s safety experience, but they do not support a like-for-like causal comparison among doses.

The primary endpoint also illustrates why an outcome definition and analysis population matter. DLTs are defined using a specified assessment period and a set of clinical criteria, while the dose-determining set depends on treatment exposure and safety evaluations. The registry record gives those broad rules, but does not report the population size or endpoint count. Without both numerator and denominator, a reader cannot estimate the observed DLT frequency from the posted primary outcome information.

The adverse-event data show why counts should be interpreted with their denominators and context. The dose groups have differing at-risk counts, and the record does not provide an adjusted analysis or a control group. Even when the affected counts are available, they cannot establish a dose-related difference or attribute an event to treatment. The listed deaths likewise require caution because cause and attribution are not reported in the record.

Finally, the registry lists response and antidrug antibody outcomes but does not post their results or statistical analyses. That separation between registered aims and posted results is important: the intended question, design, and descriptive safety counts are not substitutes for reported endpoint estimates. The record supports a careful account of what was planned and recorded, while leaving key inferential questions unresolved.

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 trial-specific limitations constrain interpretation. The registry record does not report the primary DLT count, the size of the dose-determining set, or the number of participants evaluable for each outcome. Although enrollment is listed as 48, that total does not identify the analysis denominator for the first-cycle safety endpoint. The minimum exposure criterion used to define the dose-determining set is not described.

The design is open-label and sequential, with allocation recorded as not applicable and no control arm listed. The dose groups are not randomized comparison groups. Differences in their event counts cannot be attributed to dose without accounting for potential differences in participant characteristics, treatment exposure, and follow-up; no such adjusted analysis is reported in the registry record.

The record does not report the recommended Phase 2 dose, response results, antidrug antibody results, confidence intervals, hypothesis tests, or a statistical analysis plan. Missing-data handling, interim analyses, stopping rules, and the reason for termination are also not reported. The DLT definition refers to protocol exceptions, but their details are not included in the registry record.

For the adverse-event summaries, the record lists affected counts and participants at risk, but does not establish event attribution, follow-up comparability, or the cause of deaths. The denominators for the listed serious-event term percentages are not reported. These gaps mean the summaries should be treated as descriptive and should not be extended into claims about comparative safety or treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study on the Safety of GEN1044 (DuoBody®-CD3x5T4) in Patients With Malignant Solid Tumors — NCT04424641.
• Registry record last updated 2023-07-25; status last verified 2023-07.
• Results first posted 2023-02-01.
• 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

NCT04424641 is a Genmab-sponsored, first-in-human, open-label trial of GEN1044 in patients with malignant solid tumors. It is listed as Phase 1 and Phase 2, with sequential allocation, no masking, and enrollment of 48. The registry records a start date of 2020-07-15, a primary completion date of 2021-10-29, and terminated status.

The primary endpoint is the number of participants with DLTs from Day 1 to Day 21 of the first cycle, assessed in a dose-determining set. The registry record describes the endpoint definition and group-level adverse-event counts, but does not report the primary endpoint result, a recommended Phase 2 dose, or results for the listed response and antidrug antibody outcomes. The reason for termination, analysis plan, and missing-data methods are not reported.