A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. (NCT04209465), a na phase 1 study. The primary outcome is Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D).

2. Clinical Question

The clinical question is therefore primarily about dose finding and early safety, rather than whether BDTX-189 outperforms another treatment. The registry describes a Phase 1 study in advanced solid tumors, with dose escalation across cohorts and a safety expansion. The record also lists objective response rate and progression-free survival as secondary outcomes, alongside treatment-emergent adverse events and plasma concentration. These outcomes describe preliminary activity, safety, and drug exposure; the record does not provide a controlled efficacy comparison.

3. Trial Design

MasterKey-01 is described as a Phase 1/2, open-label, two-part, multicenter study, while the registered phase is Phase 1. The study began on 2019-12-19, had a primary completion date of 2022-09-02, and is listed as terminated. Total enrollment is 91. The reason for termination is not reported in the registry record.

The dose-escalation portion enrolled cohorts with select HER2, HER3, or EGFR alterations and administered increasing doses of oral BDTX-189. The recorded groups include once-daily doses of 25 mg, 50 mg, 100 mg, 200 mg, 400 mg, 800 mg, 1000 mg, and 1200 mg, a 800 mg QD NF group, twice-daily doses of 400 mg, 600 mg, and 800 mg, and a safety-expansion group at 800 mg QD. The meanings of the NF abbreviation and the dose-escalation decision rules are not reported in the registry record.

Because the study is open-label, treatment assignment was not masked. Allocation is listed as not applicable, and the model is sequential. The dose groups are not randomized comparison arms: participants at different dose levels may differ in cohort composition, timing, or other features, and the registry does not establish their comparability. A difference in an outcome across listed groups would not by itself estimate a causal dose effect.

The study planned to evaluate safety and tolerability, pharmacokinetics, and preliminary antitumor activity. Its primary endpoint concerns dose-limiting toxicities in a DLT-Evaluable population, over a stated window after the first dose. A detailed protocol, sample-size justification, formal interim-analysis plan, and complete statistical analysis plan 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.

Only the first 6 of 13 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: DLT-Evaluable

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 14 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Dose Limiting Toxicities as a Determinant of the Recommended Phase 2 Dose (RP2D), measured over After the first dose of treatment for up to 21 days..

The primary endpoint is the number of dose-limiting toxicities, used as a determinant of the recommended Phase 2 dose. The registry defines the timeframe as after the first dose of treatment for up to 21 days. It states that certain toxicities count as dose-limiting unless they are clearly attributable to an extraneous cause, such as underlying disease. The population is identified as DLT-Evaluable.

In general, dose-limiting toxicity is used in early dose-finding research to assess whether a dose has unacceptable toxicity during a specified observation window. The count can inform decisions about dose selection alongside other safety and pharmacokinetic information. It is not, by itself, a complete description of all harms, all treatment-emergent adverse events, or antitumor activity. Nor does a count alone establish how a dose compares with another dose, particularly when cohorts are sequential rather than randomized.

The registry record does not report the numeric number of dose-limiting toxicities, the number of DLT-Evaluable participants, or the resulting recommended Phase 2 dose. It therefore does not support a quantitative summary of the primary endpoint or a reconstruction of the dose-selection decision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a dose-limiting toxicity count represent?

As a general statistical concept, an event count records how many participants meet a defined event criterion during a specified period. Here, the endpoint is the number of dose-limiting toxicities in a DLT-Evaluable population, after the first dose for up to 21 days. The registry says certain toxicities are dose-limiting unless clearly attributable to an extraneous cause, such as underlying disease. That attribution rule matters because determining whether an event meets the endpoint definition involves clinical classification, not just counting every event recorded during follow-up.

A count is interpretable only with its population and observation window. A count without the number of participants evaluated cannot show how frequently the endpoint occurred in that population. The registry does not report the numeric primary count or DLT-Evaluable denominator, so a primary-endpoint rate cannot be described from the record. No rate should be reconstructed from overall enrollment, because that enrollment is not identified as the primary endpoint denominator.

Why are the dose groups not a controlled comparison?

In general, random allocation helps balance known and unknown participant characteristics between groups, supporting a causal comparison. This study's allocation is listed as not applicable, its model as sequential, and its masking as none. Dose cohorts are therefore descriptive groups in a dose-escalation study, not randomized arms. Participants in later cohorts may have entered at different points in the study, and dose level may be related to the sequential decisions of the study. A simple difference in counts across dose groups would not isolate the effect of dose.

For the same reason, a statistical test or confidence interval for a between-dose contrast would not automatically solve the design limitation. General statistical inference quantifies uncertainty under a specified model and design; it cannot create randomization or remove unmeasured differences between cohorts. The record does not report adjusted dose comparisons or inferential analyses.

How should adverse-event counts be read?

Each listed group includes participants at risk and participants affected by serious adverse events, as well as counts for other adverse events and deaths. These are group-level descriptive entries. The number at risk provides context for the affected count, but the group sizes vary, and no controlled comparison is reported. Serious event counts should not be conflated with the primary dose-limiting-toxicity endpoint: the registry lists them separately, and does not state that every serious event met the dose-limiting definition.

The registry also lists selected serious-event terms with percentages, including pneumonia at 50.0%, Anorectal infection at 50.0%, Pneumonitis at 25.0%, Acute kidney injury at 20.0%, Pleural effusion at 20.0%, and Anemia at 20.0%. A percentage is meaningful only in relation to its denominator and event definition. The record does not fully explain the denominator for these term-level summaries or whether participants could contribute more than one term. These percentages should therefore be read as reported descriptive summaries, not as comparable risks across treatment groups.

What does a confidence interval mean?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used. A wider interval indicates less precision, while a narrower interval indicates greater precision under those assumptions. The registry record does not report confidence intervals for the primary endpoint or the listed adverse-event summaries. Without an estimate and its uncertainty, the reader cannot assess statistical precision for a primary endpoint effect.

Likewise, a p-value, when reported, addresses compatibility of data with a specified statistical null model; it does not measure clinical importance or prove causation. No analysis results or p-values are reported in the registry record. The absence of those quantities means that inferential claims should not be inferred from descriptive counts.

What is the role of planning illustrations?

In general, a sample-size calculation illustrates how many participants a future study might require under stated assumptions about an effect, significance level, allocation, and analysis method. Such a calculation is a planning tool, not evidence that the current study had a particular probability of detecting an effect. The planning assumptions associated with the study describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect specified as a fraction of the observed effect. They state that non-time-to-event illustrations use participants per arm, while time-to-event illustrations use a total number of events.

These assumptions do not establish the study's original design or justify its enrollment. The record does not report the protocol's sample-size justification, and the study was not a randomized two-arm comparison. The planning illustrations should not be interpreted as observed power, as evidence of treatment benefit, or as a replacement for a prospective design rationale. Any recalculated summary based on posted data would be an unadjusted calculation and would not override the sponsor's own analysis if a discrepancy were identified. The registry record does not provide sponsor analysis results for the primary endpoint.

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("25 mg QD", "50 mg QD", "100 mg QD", "200 mg QD", "400 mg QD", "800 mg QD Fasted")
n      <- c(1, 1, 1, 2, 10, 18)
events <- c(0, 0, 0, 0, 0, 0)
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  25 mg QD  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  50 mg QD  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  100 mg QD  1  0  0.0  0.0  97.5  0.0  79.3  1.3  84.2
ARM  200 mg QD  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  400 mg QD  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5
ARM  800 mg QD Fasted  18  0  0.0  0.0  18.5  -0.0  17.6  0.1  17.6

11. Multiplicity, Missing Data and Analysis Populations

The study has several objectives and outcomes: dose-limiting toxicities are the primary endpoint, while secondary outcomes include treatment-emergent adverse events, plasma concentration, objective response rate, and progression-free survival. In general, testing multiple outcomes can increase the chance of at least one apparently positive result if each is assessed as a separate confirmatory test. A prespecified multiplicity strategy may address that issue. Such a strategy is not reported in the registry record, and no outcome-analysis results are posted for evaluating how multiplicity was handled.

The registry identifies the primary analysis population as DLT-Evaluable, but it does not report its size or a detailed definition. Total enrollment is 91; that figure should not be treated as the endpoint denominator without confirmation. The record does not describe missing-data rules, participant exclusions from the primary analysis, or how incomplete follow-up was handled.

In general, missing observations can affect estimates when the reason data are absent is related to participant characteristics, treatment, or outcomes. Complete-case summaries may represent a different subset from all enrolled participants. Without a reported missing-data approach and endpoint-specific denominator, the extent and potential direction of any such effect cannot be assessed.

Formal interim analyses, stopping rules, and the detailed statistical analysis plan are not reported in the registry record. The study's terminated status is recorded, but its reason and any relationship to analysis or missing follow-up are not reported. These omissions limit assessment of prespecification and completeness; they do not establish that a particular analysis method was or was not used.

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: pneumonia (50.0%), anorectal infection (50.0%), pneumonitis (25.0%), acute kidney injury (20.0%), pleural effusion (20.0%).

The serious adverse-event entries are counts by dose group. Each group reports the number at risk and the number affected, which helps place the count in context. For example, the 400 mg QD group lists 10 participants at risk and 2 affected, while the 800 mg QD NF group lists 13 at risk and 1 affected. The safety-expansion 800 mg QD group lists 17 at risk and 4 affected. These figures describe the posted groups; they are not randomized comparisons.

Group sizes differ, and the record does not report statistical comparisons between doses. Counts should therefore not be read as evidence that one dose is safer or less safe than another. Serious adverse events are also distinct from the primary dose-limiting-toxicity outcome: the registry does not state that all serious events qualified as dose-limiting toxicities.

The listed term percentages are reported as pneumonia 50.0%, Anorectal infection 50.0%, Pneumonitis 25.0%, Acute kidney injury 20.0%, Pleural effusion 20.0%, and Anemia 20.0%. The denominator and overlap among terms are not fully described in the registry record. The death counts are also descriptive; cause and treatment attribution are not reported. These entries do not by themselves establish that BDTX-189 caused any particular event.

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

The record supports a description of the study's design and posted safety information. It identifies a Phase 1, open-label, sequential study of orally administered BDTX-189 in advanced solid tumors with select ErbB alterations. It also describes dose escalation and a safety-expansion group, and lists a primary endpoint based on dose-limiting toxicities during a defined early treatment window.

The record does not report a numeric result for that primary endpoint, the DLT-Evaluable denominator, or the recommended Phase 2 dose. It therefore does not show the primary dose-finding result in a way that can be quantitatively assessed. The listed serious adverse-event counts and terms offer descriptive safety information, but do not establish comparative risks or causal attribution. The secondary outcome list includes pharmacokinetics and preliminary antitumor activity; corresponding numeric outcome results are not reported in the registry record.

In general, early-phase dose-escalation studies can characterize initial tolerability and inform further study. Their sequential cohorts and lack of randomized control limit direct comparisons across doses and do not establish comparative treatment effects. Findings in the enrolled population also do not automatically generalize to other populations or settings.

The study's termination status is reported, but the reason is not. It should not be interpreted as evidence of a particular safety, efficacy, operational, or business outcome. Similarly, the absence of a reported result is not itself evidence that no events occurred or that an endpoint was negative. It means the registry record does not provide that result for readers to evaluate.

Accordingly, the posted information can be read as a record of study conduct and selected adverse-event summaries, not as a complete assessment of benefit, harm, or dose selection. Any conclusion beyond those descriptive details would require analysis results and context not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates a statistical distinction between dose finding and comparative evaluation. In a sequential Phase 1 design, cohorts receive escalating doses as part of an early safety assessment. The central question is not the same as in a randomized trial designed to compare treatment with a control. Dose groups can inform the development process, but their outcomes should not be treated as though participants were randomly assigned across doses.

The endpoint definition also matters. A dose-limiting-toxicity count is tied to an evaluation population, a classification rule, and an observation window. The registry specifies a DLT-Evaluable population and a period after the first dose for up to 21 days, but does not report the result or denominator. That gap shows why an endpoint label alone is insufficient: interpretation depends on the event criteria and the number of participants actually assessed.

Safety summaries further demonstrate why raw counts need context. Different cohort sizes can make counts difficult to compare, while serious adverse events, dose-limiting toxicities, and deaths are distinct categories unless the record explicitly links them. Term-level percentages also require a clear denominator and rules for repeated or overlapping events. Those details are not fully.

Finally, a terminated study with a listed enrollment and completion date can still have important outcome information absent from the registry record. The status alone does not explain why the study ended or what the results were. Statistical interpretation should separate what is documented—design features and descriptive counts—from what cannot be assessed, including the numeric primary result, its precision, and the basis for dose selection.

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 the posted results is that the registry record does not include a numeric primary endpoint result, the DLT-Evaluable denominator, or a reported recommended Phase 2 dose. This prevents quantitative assessment of the stated dose-finding endpoint.

The study is open-label and sequential, with allocation listed as not applicable. There is no like-for-like randomized control comparison, so the listed dose groups cannot support a straightforward causal contrast. Their sizes vary, and the record does not provide adjustment methods or inferential comparisons.

The record lists serious adverse-event counts, event terms, and deaths, but does not fully specify term-level denominators, overlap among event categories, or attribution. Serious adverse-event counts should not be substituted for dose-limiting-toxicity results. Further detail on the DLT definition, assessment procedures, and endpoint-specific follow-up is not reported in the registry record.

Although total enrollment is 91, the number assessed for each outcome is not reported. Missing-data handling, analysis populations beyond the DLT-Evaluable label, and exclusions are not described. The registry also does not report the detailed statistical analysis plan, a sample-size justification, multiplicity handling, or interim-analysis methods.

The study is listed as terminated, but the reason is not reported. The available record therefore cannot explain whether termination affected data collection or analysis. These limitations leave substantial uncertainty about the completeness and precision of the outcome evidence, without implying a particular direction of results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. — NCT04209465.
• Registry record last updated 2025-04-17; status last verified 2024-04.
• Results first posted 2025-04-17.
• 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

NCT04209465 is a Phase 1 study of oral BDTX-189 in patients with advanced solid tumors and select ErbB alterations. It is described as open-label, sequential, and multicenter, with dose escalation and a safety expansion. Enrollment is 91; the study began on 2019-12-19, had a primary completion date of 2022-09-02, and is listed as terminated.

The primary endpoint is the number of dose-limiting toxicities in a DLT-Evaluable population after the first dose for up to 21 days. The record does not report a numeric primary result, the endpoint denominator, or a recommended Phase 2 dose. Secondary outcomes concern adverse events, plasma concentration, objective response rate, and progression-free survival.

Serious adverse-event counts are reported by dose group, but the groups are not randomized comparators. The reason for termination and detailed statistical methods, including missing-data and multiplicity handling, are not reported in the registry record.