Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment (NCT04820023), a non-randomized phase 1, phase 2 study. The primary outcome is (Part 1) Incidence of Adverse Events and Clinical Laboratory Abnormalities Defined as Dose-limiting Toxicities (DLTs).

2. Clinical Question

3. Trial Design

This is a phase 1/2, open-label study of BBT-176 in advanced NSCLC following progression after EGFR TKI therapy. The registry describes it as the first-in-human study of BBT-176. Its stated aims are to investigate safety and tolerability in Part 1 and evaluate anti-tumor activity in Part 2. The registered design is non-randomized and single-group, with no masking. The planned enrollment listed in the record is 45.

The intervention groups represent oral BBT-176 regimens at different doses, given QD or BID. Listed dose groups are 20mg QD, 80mg QD, 160mg QD, 320mg QD, 480mg QD, 600mg QD, 160mg BID, 200mg BID, and 240mg BID. Because there is no randomized control group, the groups are not a like-for-like comparison. Any observed variation between them could reflect differences in participants, follow-up, or other factors as well as dose; the registry design alone cannot distinguish these explanations.

The primary outcome concerns DLTs in Part 1, with a timeframe of 21 days from first dosing. Registered secondary outcomes include Part 1 objective response rate and pharmacokinetic measures, including peak concentration and area under the concentration-time curve. Part 2 outcomes include duration of response, adverse events, BBT-176 concentrations, and progression-free survival. The registry record lists nine outcome measures but no analyses.

The study start date is 2021-04-02, and the primary completion date is 2023-11-29. The registry status is terminated. The reason for termination, details of the transition between study parts, and the number of participants contributing to each outcome 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 9 groups are shown.

Overall Study

Reasons for not completing this period:

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: Each treatment cycle is 21 days.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as (Part 1) Incidence of Adverse Events and Clinical Laboratory Abnormalities Defined as Dose-limiting Toxicities (DLTs), measured over 21 days from the first dosing.

The primary endpoint is the incidence of adverse events and clinical laboratory abnormalities defined as DLTs in Part 1. It is measured as a count of participants. The stated assessment timeframe is 21 days from first dosing. The registry description limits DLTs to toxicity not attributable to the disease or disease-related processes under investigation, occurring from the first dose in dose-escalation cohorts as defined in the protocol.

In early-phase studies, a DLT endpoint is used to characterize tolerability over a specified assessment period while doses are being evaluated. It focuses attention on events meeting a protocol definition rather than treating every event as a DLT. The endpoint can inform dose-escalation decisions within a study, but the registry record does not give the protocol definition beyond the description above, nor does it report a DLT count or analysis result.

A count of participants is different from a count of individual events: one participant may experience more than one event, but a participant-based endpoint records whether participants meet the endpoint definition. The registry identifies the unit as participants. It does not report the result by dose group for this primary endpoint, the analysis population, or how incomplete follow-up was handled. The posted adverse-event counts are not interchangeable with the primary DLT endpoint, because the primary endpoint uses a specific definition and timeframe.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods can help distinguish what a study estimates from what its design can support. In this study, the registry reports a non-randomized, single-group design with no masking. The groups received different BBT-176 dose regimens, but there is no separate randomized control group. This matters because a comparison between groups assigned without randomization can be affected by differences in participant characteristics, follow-up, or other circumstances. A difference in observed outcomes is not, by itself, evidence that dose caused that difference.

What does a participant count mean?

The primary endpoint is specified as a count of participants with DLTs, not a count of all DLT events. A participant-based measure generally records whether each participant met the endpoint definition during the specified assessment period. The endpoint description covers adverse events and clinical laboratory abnormalities considered toxicity, excluding toxicity attributed to the disease or disease-related processes under investigation. The listed timeframe is 21 days from first dosing. The protocol’s full DLT criteria are not reported in the registry record, so the endpoint cannot be reconstructed in greater detail from the public summary.

Counts need context. The number of participants in a dose group affects how many events could be observed, and the registry reports different group sizes in its safety summary. Counts alone do not express an individual participant’s probability of an event or account for follow-up time. A proportion or rate can be useful in other settings, but a new estimate should not be inferred without a stated denominator, endpoint definition, and analysis population. The registry’s primary endpoint result is not reported.

Why is uncertainty important?

In general, a confidence interval describes a range of estimates that are compatible with the observed data under the analysis assumptions. It communicates precision as well as the direction and size of an estimate. A narrow interval usually indicates greater precision than a wide interval, while a wide interval leaves more uncertainty about the underlying value. The registry record does not report confidence intervals for the primary endpoint or the safety counts. Without an estimate and its uncertainty, the precision of a treatment effect or event frequency cannot be assessed from the posted information.

In general, a p-value assesses how compatible data are with a specified null hypothesis under an analysis model. It does not measure the probability that a hypothesis is true, nor does it establish clinical importance. No outcome analysis or p-value is reported in the registry record. The registry record also does not report a statistical analysis plan, so the intended tests, model specifications, or decision criteria cannot be inferred.

What can the safety summary show?

The registry lists participant counts with serious adverse events and with other adverse events by dose group, along with deaths. These are descriptive safety summaries, not randomized comparisons. Serious adverse events and other adverse events are distinct categories in the record; neither category should be treated automatically as the DLT endpoint. A serious event may or may not meet the DLT definition, and an event classified as a DLT need not be described by the same category in the safety summary. The registry does not report an analysis linking these categories.

Adverse events can also be summarized by preferred or reported terms. The registry lists selected terms and percentages, but the denominator and method used for those percentages are not stated in the summary. Event-term percentages are not evidence of a dose relationship unless the data, denominators, and analysis support that interpretation. No such analysis is reported in the registry record.

How should planning calculations be understood?

In general, a sample-size calculation uses assumptions about the effect to be detected, variability or event frequency, significance level, power, allocation, and analysis method. Its output is a planning illustration rather than an observed result. The registry record’s sample-size assumptions describe an illustration based on the observed effect, with two-sided significance level 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 outcomes, the description says the calculation concerns total events, while other calculations are described as participants per arm.

These assumptions do not describe the trial’s own design: the registered study is non-randomized and single-group, and there is no like-for-like two-arm randomized comparison. No numerical sample-size outputs are reported in the registry record. The assumptions therefore cannot be used to claim that the study had a particular power, or that any endpoint was adequately powered. Sample-size illustrations are not observed power, and they do not replace a prespecified analysis plan.

Over-dispersion is a general issue for count data when observed variability exceeds what a simple count model assumes. If present, a model that ignores it can give uncertainty estimates that are too small. It is not possible to assess over-dispersion from the registry summary because no count model, participant-level data, or analysis results are reported. More broadly, the choice of statistical method, handling of repeated events, censoring, and missing observations is not reported in the registry record. Statistical explanations of these methods are general and do not indicate that any particular method was used in this study.

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("20mg QD", "80mg QD", "160mg, QD", "320mg, QD", "480mg, QD", "600mg, QD")
n      <- c(4, 3, 4, 3, 8, 3)
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  20mg QD  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  80mg QD  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  160mg, QD  4  0  0.0  0.0  60.2  0.0  49.0  0.5  52.2
ARM  320mg, QD  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2
ARM  480mg, QD  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6
ARM  600mg, QD  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes across Part 1 and Part 2, including objective response rate, pharmacokinetic measures, duration of response, adverse events, BBT-176 concentrations, and progression-free survival. When several outcomes or comparisons are analyzed, multiplicity is a general concern: the chance of at least one apparently notable finding can increase as the number of tests increases. Researchers may address this through a prespecified hierarchy, adjustment, or another strategy. The registry record does not report a multiplicity strategy, a hierarchy among outcomes, or an analysis plan.

The record lists nine outcome measures but reports no analyses. Results for the primary endpoint and listed secondary outcomes, including estimates and uncertainty, are not reported in the registry record. It is therefore not possible to determine which outcomes were analyzed, whether all planned analyses were completed, or how any multiplicity was handled.

Missing-data methods are not reported in the registry record. The record does not state how participants with incomplete follow-up, unavailable laboratory assessments, or missing outcome information were handled. It also does not specify an analysis population for the primary or secondary outcomes, such as which participants were included in each analysis. Without these details, the reader cannot assess whether outcome estimates might depend on exclusions or incomplete observation.

The listed enrollment is 45, but the registry does not give the number contributing to each endpoint analysis. Enrollment and analysis populations can differ, so enrollment alone does not establish the denominator for an outcome. The record also does not report interim analyses or stopping rules; their presence or absence should not be inferred.

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: pleural effusion (33.3%), pericardial effusion (33.3%), neutrophil count decreased (33.3%), gastritis (25.0%), pneumonia (25.0%).

The registry’s safety summary gives counts of participants at risk and counts affected, separately for serious adverse events and other adverse events, with deaths also listed. For serious adverse events, the counts are: 20mg QD, 0 of 4; 80mg QD, 0 of 3; 160mg QD, 2 of 4; 320mg QD, 1 of 3; 480mg QD, 4 of 8; 600mg QD, 1 of 3; 160mg BID, 3 of 5; 200mg BID, 6 of 9; and 240mg BID, 6 of 6. The corresponding counts for other adverse events are 3 of 4, 2 of 3, 3 of 4, 3 of 3, 8 of 8, 3 of 3, 4 of 5, 9 of 9, and 6 of 6, respectively.

Deaths are listed as 1 in the 160mg BID group and 1 in the 240mg BID group; the other listed groups have 0. The registry also names serious-event terms with percentages: pleural effusion, pericardial effusion, and neutrophil count decreased at 33.3% each; gastritis and pneumonia at 25.0% each; and COVID-19 related Pneumonia at 20.0%. Denominators for those term percentages are not reported in the registry record.

These are descriptive figures across non-randomized dose groups. Different group sizes and the absence of a randomized control mean the counts do not establish comparative risk or a causal dose effect. They also do not identify which events met the primary DLT definition.

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

The posted record establishes that BBT-176 was studied in a first-in-human, phase 1/2, open-label trial among patients with advanced NSCLC after progression following EGFR TKI therapy. It identifies the study aims, dose regimens, primary DLT endpoint, and descriptive safety counts. It also shows that the registry status is terminated. These registry entries describe the study and its posted record; they do not provide a complete statistical evaluation of the treatment.

The primary endpoint result is not reported in the registry record. Analyses of the listed outcomes are also not reported. As a result, the public registry information does not show an estimated DLT frequency, an estimate of anti-tumor activity, or the precision of such an estimate. The safety counts offer descriptive information about participants in the listed groups, but they cannot establish how outcomes would compare with a control treatment.

A non-randomized, single-group design is not suited to a causal comparison between BBT-176 and an alternative treatment. The dose groups are not randomized comparison arms, and the posted counts do not account for differences in group composition or other factors. The registry’s listed term percentages also lack denominators in the summary, which limits their interpretation as measures of frequency.

The terminated status does not by itself explain the study’s course or outcome. The reason for termination, the analysis populations, missing-data handling, and statistical analysis plan are not reported in the registry record. Consequently, the posted information should not be used to claim either benefit or lack of benefit, or to draw conclusions about a treatment effect. It supports a description of the design and recorded safety summaries, while leaving the principal outcome analyses and their uncertainty unresolved.

14. Why This Trial Matters Statistically

This trial is statistically notable for the questions it was designed to address at different stages. The registry distinguishes Part 1 safety and tolerability aims from Part 2 anti-tumor activity aims, and defines a primary DLT endpoint for Part 1. That distinction matters because safety events, DLTs, and tumor activity are different outcomes with different definitions and interpretations. A general adverse-event count cannot stand in for a protocol-defined DLT outcome or an efficacy analysis.

The record also illustrates the limits of interpreting multiple dose groups without randomization. Dose-specific summaries can describe what was observed among participants in each group, but they do not provide the protection against confounding that a randomized control comparison is designed to offer. Unequal group sizes make raw counts particularly difficult to compare, and the registry does not post adjusted estimates or uncertainty intervals.

For clinical researchers and biostatisticians, the registry highlights why outcome definitions, analysis populations, missing-data procedures, and multiplicity plans matter. Those details help readers evaluate whether reported estimates answer the stated question and how robustly they are supported by the data. In this record, the primary endpoint result and outcome analyses are not reported, and methods for handling missing information or multiple outcomes are not reported.

The study’s posted status and safety counts remain useful descriptive information, but they are not a substitute for a complete analysis. A careful reading separates what the record documents—design, endpoint wording, regimens, and safety counts—from what it does not report, including primary endpoint results, comparative effects, and the statistical uncertainty around 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 main limitation for statistical interpretation is that the registry record does not report analyses for the primary endpoint or the listed outcomes. No DLT count or estimate is posted, so the stated primary question cannot be answered from the record’s outcome results. The listed safety counts are descriptive and do not include reported statistical comparisons or uncertainty intervals.

The design is non-randomized and single-group, with no separate randomized control group. Comparisons across dose groups are not like-for-like control comparisons. Group sizes vary, and the record does not report participant-level characteristics or adjusted analyses that might help explain differences in the observed counts. These limitations prevent causal interpretation of dose-group differences.

The registry’s description of the primary endpoint refers to the protocol’s DLT definition, but the full protocol criteria are not reported in the registry record. It is not clear from the record which reported adverse events met that definition. The record also does not state the analysis populations, missing-data handling, multiplicity approach, or statistical analysis plan. Denominators for the listed serious-event term percentages are not reported in the summary.

The status is terminated, but the reason is not reported in the registry record. The record does not provide enough information to infer why the study ended, whether termination affected follow-up, or how many participants contributed to each outcome. These are limits of what can be concluded from the registry information and do not establish that a particular outcome or event was absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment — NCT04820023.
• Registry record last updated 2025-06-06; status last verified 2025-06.
• Results first posted 2025-06-06.
• 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

NCT04820023 is a phase 1/2, open-label, non-randomized, single-group study of oral BBT-176 in advanced NSCLC following progression after EGFR TKI treatment. The registry describes it as first-in-human and lists an enrollment of 45. Dose regimens include QD and BID schedules across multiple dose groups.

The Part 1 primary endpoint is the count of participants with adverse events and clinical laboratory abnormalities defined as DLTs during 21 days from first dosing. The registry also lists secondary safety, pharmacokinetic, response, and time-to-event outcomes. Its status is terminated; the reason is not reported in the registry record.

The record includes descriptive serious and other adverse-event counts by dose group, but no outcome analyses. Primary endpoint results, analysis populations, missing-data methods, and the statistical analysis plan are not reported in the registry record. The posted information therefore supports description of the design and safety summaries, not a comparative treatment-effect conclusion.