A Study of TAS3351 in NSCLC Patients With EGFRmt: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of TAS3351 in NSCLC Patients With EGFRmt (NCT05765734), a non-randomized phase 1 study. The primary outcome is Part A1: Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAE).

2. Clinical Question

3. Trial Design

The registry describes a first-in-human, open-label Phase 1/2 study of TAS3351 in participants with advanced NSCLC and EGFR mutations. Its phase field lists PHASE1. Allocation was non-randomized, masking was none, and the model was single group. The study record lists 18 participants enrolled, with a status of terminated. The start date was 2023-05-25 and the primary completion date was 2025-03-14. The reason for termination is not reported in the registry record.

Part A1 was dose escalation. The listed groups received TAS3351 at 50 mg, 100 mg, 200 mg, 350 mg, or 500 mg, orally once daily on Days 1-21 of each 21-day cycle. The registry gives maximum treatment durations of 66 days, 126 days, 94 days, 46 days, and 87 days for those respective groups. A 700 mg dose group is described as planned, but the registry's posted adverse-event figures do not include that group. The dose-escalation decision rules and the basis for selecting dose levels are not reported in the registry record.

Part A2 backfill was planned when a dose level in Part A1 was considered safe and preliminary antitumor activity had been observed. Parts B and C were planned to enroll participants with C797S EGFR mutations at the recommended Phase 2 dose established in Part A. The registry does not establish that these planned parts were conducted. Allocation was not randomized, so observed differences between dose groups should not be treated as controlled comparisons: group membership may reflect the study's dose-escalation process rather than random assignment. The registry record does not report a separate comparator or masking procedure.

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 18 participants received at least one dose of TAS3351 in Part A1. The study was originally designed to be conducted in three parts: Phase 1: Part A (including Part A1: Dose Escalation and Part A2: Backfill) and Part B (Dose Expansion); Part C (Phase 2). However, as the study was terminated early, no participants were further enrolled in Parts A1 dose expansion for 700 milligrams (mg), A2, B, or C of the study and these parts were not conducted.

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: The all treated population included all participants who received at least one dose of the study drug.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: The all treated population included all participants who received at least one dose of the study drug.

6. Primary Endpoint

The registry lists the primary outcome as Part A1: Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAE), measured over From first dose of the study drug up to 30 days after last dose (up to 21.7 months).

The primary endpoint is the number of participants in Part A1 with treatment-emergent adverse events (TEAEs). It is a count of participants, rather than a measure of event severity, duration, or frequency per participant. The registry defines a TEAE as an adverse event that started or worsened at or after the first dose and within 30 days after the last dose of study drug. An event did not need to be considered causally related to TAS3351 to meet that definition.

The endpoint uses the all-treated population: participants who received at least one dose of study drug. Its timeframe runs from the first dose through 30 days after the last dose, with the registry giving an overall maximum of 21.7 months. Counting participants with events is a way to describe the proportion of treated participants who experienced at least one event, though the posted endpoint is specified as a count. By itself, that count does not distinguish between a participant with one event and a participant with multiple events, nor does it indicate whether an event was serious or treatment-related.

Safety monitoring is central to early clinical development because it describes the kinds and extent of adverse events observed while doses are being explored. The registry lists the TEAE count as the primary endpoint, but a numerical result for that endpoint is not reported in the registry record. Separate serious and other adverse-event figures are posted by dose group; those figures should be read according to their own categories rather than substituted for an unavailable TEAE result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

For a count endpoint, the direct descriptive result is the number of participants meeting the endpoint definition within the population and timeframe. In this study, the primary endpoint concerns participants with TEAEs in the all-treated population. A count is straightforward to interpret, but it does not express the number of events per participant or distinguish event severity. The registry's separate serious and other adverse-event listings provide additional categories, but they are not interchangeable with the primary TEAE endpoint.

What does a single-group design allow?

In general, a single-group study can describe outcomes observed among participants receiving the study intervention. When dose groups are not randomized, differences across them can also reflect how participants entered each dose group, the sequence of dose escalation, or other differences among participants. A randomized control group is one way to support a direct comparison by assigning participants to groups through chance. This study is listed as non-randomized and single group, so the dose groups do not form a like-for-like control comparison.

Open-label means the study was not masked according to the registry. In general, knowledge of treatment can affect reporting or assessment, depending on the outcome and how it is measured. The record does not report procedures intended to limit such effects. This consideration does not invalidate the posted counts, but it is relevant when interpreting subjective reports and when assessing the design's ability to make comparative claims.

How should uncertainty be understood?

In general, a confidence interval describes a range of values compatible with the observed data under a specified statistical method and assumptions. Narrower intervals indicate greater precision, while wider intervals indicate more uncertainty. No confidence intervals for the posted adverse-event counts are reported in the registry record. Without such intervals, the counts can be described, but their statistical precision cannot be quantified from the registry record. The small group counts also mean that changes in the experience of a participant could materially alter a group's descriptive result.

In general, p-values assess how compatible data are with a specified null hypothesis under a statistical model. They do not measure the size or importance of an effect, and they do not correct for design limitations. The registry record lists zero analyses; no p-values or inferential comparisons are reported. Therefore, there is no reported hypothesis test with which to assess statistical evidence for a difference between dose groups.

What do planning illustrations mean?

Any sample-size planning illustration based on an observed effect is a hypothetical design calculation, not a result observed in participants and not a measure of the study's power after it has been completed. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event planning, the illustration is expressed as a total number of events using the Schoenfeld approach; other illustrations are expressed as participants per arm. These assumptions describe an illustration, not a protocol plan. The trial's own sample-size justification is not reported in the registry record. No sample-size illustration should be read as observed power.

In general, over-dispersion occurs when count data vary more than a model assumes. If a count model assumes less variability than the data contain, its uncertainty estimates may be too small. The primary endpoint is a count of participants with an event, not a count of repeated events, and no model or dispersion estimate is reported. Whether over-dispersion was assessed is not reported in the registry record; it should not be assumed that a particular count model was used.

What can be inferred from adverse-event summaries?

Participant counts affected by serious or other adverse events are descriptive safety summaries. They do not show the number of total events, the length of time each participant was observed, or causal attribution unless those details are separately defined and reported. The TEAE definition explicitly does not require a causal relationship to study drug. The registry's summary therefore records events meeting the timing definition, not necessarily events judged to have been caused by TAS3351. The statistical analysis plan, any interim analyses, and any methods for handling missing outcome data are not 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 A1: Dose Escalation: 50 mg", "Part A1: Dose Escalation: 100 mg", "Part A1: Dose Escalation: 200 mg", "Part A1: Dose Escalation: 350 mg", "Part A1: Dose Escalation: 500 mg")
n      <- c(3, 3, 3, 5, 4)
events <- c(2, 3, 3, 4, 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  Part A1: Dose Escalation: 50 mg  3  2  66.7  9.4  99.2  20.8  93.9  19.4  93.2
ARM  Part A1: Dose Escalation: 100 mg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Part A1: Dose Escalation: 200 mg  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Part A1: Dose Escalation: 350 mg  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7
ARM  Part A1: Dose Escalation: 500 mg  4  3  75.0  19.4  99.4  30.1  95.4  28.4  94.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: the primary TEAE count and secondary measures that include response rate, duration of response, disease control, progression-free survival, overall survival, and plasma exposure measures. It reports 32 outcome measures and zero analyses. The registry record does not report how these outcomes were prioritized or whether statistical tests were planned for them. A multiplicity strategy, such as a prespecified adjustment or hierarchy for interpreting several tests, is not reported in the registry record.

In general, when many statistical tests are performed, the chance of obtaining at least one apparently notable result by chance can increase. Adjustment methods or a prespecified testing order can address that issue for inferential claims. This general concern does not establish that testing occurred in this study: the record lists zero analyses, and no inferential results are posted. The analysis plan and any interim-analysis procedures are not reported in the registry record.

The all-treated population for the primary endpoint is defined as participants who received at least one dose. The registry does not report how missing safety observations, incomplete follow-up, or participants who stopped treatment were handled in analyses. The maximum duration listed for individual dose groups differs, and the primary endpoint timeframe is stated as extending through 30 days after the last dose, up to 21.7 months. The record does not explain how variation in observation time was considered when comparing or summarizing groups.

Missing-data assumptions, imputation procedures, and sensitivity analyses are not reported in the registry record. Without those details and numerical endpoint results, it is not possible to assess whether incomplete data affected the posted summaries. The listed participant counts remain descriptive of the registry's reported categories and should not be read as a complete account of all analysis decisions.

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: tumour pain (33.3%).

The serious adverse-event figures give, for each listed dose group, the number at risk and the number affected. The 50 mg group lists 3 at risk and 0 affected; 100 mg lists 3 and 0; 200 mg lists 3 and 1; 350 mg lists 5 and 0; and 500 mg lists 4 and 0. These figures describe participants, not the total number of serious events. A participant may have had more than one event, but event totals are not reported in these figures.

The other adverse-event figures are separate: the 50 mg group lists 3 at risk and 2 affected; 100 mg lists 3 and 3; 200 mg lists 3 and 3; 350 mg lists 5 and 4; and 500 mg lists 4 and 3. They should not be added to the serious-event counts to infer a number of unique participants, because the record does not state whether categories overlap or provide a combined participant-level count. The registry lists zero deaths in each of these dose groups in the adverse-event summary.

Tumour pain appears among the top serious adverse-event terms at 33.3%. The registry does not give a dose-group breakdown or additional denominator details alongside that term in the record. The term percentage should not be treated as an estimate of causal risk from TAS3351. The endpoint definition includes events regardless of whether they were considered related to study drug.

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

The registry record describes a non-randomized, open-label, single-group Phase 1 study with dose-escalation groups and reports participant counts for serious and other adverse events at the listed doses. These data can help readers understand what safety events were recorded in those groups. They do not establish a causal relationship between TAS3351 and any event, because the TEAE definition does not require that relationship and no causal-attribution results are reported.

The counts do not show whether one dose is safer than another. Dose groups were not randomized, participant numbers are limited, and no controlled comparison is available. The data also do not show whether TAS3351 improves response, disease control, progression-free survival, or overall survival. Although those outcomes are listed as secondary outcomes, their numerical results are not reported in the registry record. A result for the primary TEAE count is also not reported in the registry record.

The record identifies the study as terminated, but does not report why. That status alone does not explain whether termination was related to safety, efficacy, operational issues, or another reason. Planned backfill and later study parts are described, but their completion is not established by the information in the record. The listed safety counts should therefore be interpreted as the available group-level summaries, not as a complete narrative of study conduct or sponsor conclusions.

In general, early dose-escalation studies are designed to characterize experience across dose levels and inform later development. Such studies can generate descriptive evidence and questions for further study, but without a randomized comparator they cannot isolate a treatment effect from other explanations. The registry results do not provide a basis for medical advice or a conclusion about whether TAS3351 is beneficial or harmful. They document specific reported safety counts and leave important efficacy, causal, and analysis questions unanswered.

14. Why This Trial Matters Statistically

This study is statistically notable as a first-in-human dose-escalation study in a defined NSCLC population with acquired C797S EGFR mutations. Its design illustrates the difference between describing events in dose groups and estimating a comparative treatment effect. Because the study is non-randomized and single group, the listed dose-level summaries are useful as descriptions of the participants observed, but they do not have the protection against confounding that random allocation can provide.

The primary endpoint is a participant count for TEAEs, and the registry gives a clear time-based definition and an all-treated population. Those features matter because an endpoint's population and observation window determine what its count represents. At the same time, the record does not provide the numerical primary result, an inferential analysis, or uncertainty estimates. The distinction between a specified endpoint and a posted result is important: an outcome can be named in a registry without its result being available in the record.

The adverse-event summaries also show why category definitions and denominators matter. Serious and other event counts are presented separately, while the record does not provide a combined participant-level count or enough detail to reinterpret the listed serious term percentage as a dose-specific risk. Statistical interpretation depends on keeping each summary tied to the population and definition it actually describes.

Finally, the registry lists numerous secondary outcomes but zero analyses. This makes it especially important to distinguish planned or listed outcomes from analyzed results and to avoid claims that the posted record cannot support. The case highlights how transparent reporting of analysis plans, missing-data handling, and complete numerical outcomes would improve readers' ability to assess precision and interpretability.

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 registry record has important limitations for interpreting results from this study. It lists 18 participants enrolled, but the posted adverse-event figures cover five Part A1 dose groups and do not include the planned 700 mg group. The record does not explain the status of the other planned components or establish whether Parts A2, B, or C were conducted. The study is marked terminated, but the reason is not reported in the registry record.

The primary endpoint is defined, but its numerical result is not reported in the registry record. Numerical results for the listed secondary efficacy, survival, and drug-exposure outcomes are also not reported in the registry record. The registry lists 32 outcome measures and zero analyses, limiting the available basis for statistical interpretation beyond the posted adverse-event summaries.

The non-randomized, open-label design has no concurrent control group, so it cannot support a like-for-like comparison of dose groups or a controlled estimate of treatment effect. The record does not report confidence intervals, p-values, a statistical analysis plan, sample-size justification, interim analyses, or methods for missing data. It also does not explain how differences in follow-up duration were handled. The posted group counts are therefore descriptive, with precision and completeness difficult to assess from the registry record alone.

The safety summaries do not give total event counts or establish whether serious and other categories overlap at the participant level. The registry's definition of TEAE includes events without requiring a causal relationship to study drug. The serious-term percentage for Tumour pain lacks a reported dose-group breakdown in the registry record for this record. These limitations restrict interpretation of both the frequency and attribution of adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of TAS3351 in NSCLC Patients With EGFRmt — NCT05765734.
• Registry record last updated 2026-04-02; status last verified 2026-02.
• Results first posted 2026-04-02.
• 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

NCT05765734 is a first-in-human, open-label study of TAS3351 in advanced NSCLC with EGFR mutations. The registry lists PHASE1, non-randomized allocation, no masking, a single-group model, 18 participants enrolled, and a terminated status. The primary endpoint is the number of Part A1 participants with TEAEs, defined by timing rather than required causal attribution. Five dose groups have posted serious and other adverse-event participant counts; Tumour pain is listed among the top serious adverse-event terms at 33.3%. The registry lists 32 outcome measures and zero analyses. Numerical results for the primary endpoint and the listed secondary efficacy outcomes are not reported in the registry record, and the reason for termination is not reported in the registry record.