Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations (NCT04579380), a na phase 2 study. The primary outcome is Confirmed Objective Response Rate (cORR) as Assessed by Investigator.

2. Clinical Question

3. Trial Design

This is a phase 2, single-group basket study of tucatinib in combination with trastuzumab for previously treated solid tumors with HER2 alterations. The registry lists an enrollment of 217. It describes the study as active, not recruiting, and records a start date of 2021-01-11 and a primary completion date of 2023-11-01. These registry dates describe the study record; they do not establish that every outcome has been reported.

All participants receive tucatinib and trastuzumab. Fulvestrant is added for participants with hormone-receptor-positive HER2-mutant breast cancer. The study description includes solid tumors that are metastatic or cannot be completely removed with surgery. The listed disease categories span several tumor types, consistent with the basket design. The registry does not provide a separate control group, randomized allocation, or masking; masking is listed as none and allocation as not applicable.

The primary outcome is confirmed objective response rate assessed by investigators. The response-evaluable population is defined as participants with measurable disease who had a baseline disease assessment, received study treatment, and either had a post-baseline disease assessment or stopped treatment because of documented disease progression. The registry record’s population description ends mid-phrase, so the remainder of its eligibility wording is not reported in the registry record.

Secondary outcomes include investigator-assessed disease control rate, duration of response, and progression-free survival; overall survival; and several measures of treatment-emergent adverse events, laboratory abnormalities, dose modifications due to adverse events, and adverse events of special interest. The record lists 11 outcome measures and no analysis records. A detailed statistical analysis plan, sample-size justification, and the planned handling of interim analyses 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.

Before assignment: A total of 217 participants were enrolled into 9 separate cohorts based on tumor histology and HER2 alteration status. All 217 participants were treated. Results reported are based on the primary completion date (PCD) of the study; data for only those secondary outcome measures are reported for which analyses were complete at PCD. Remaining outcome measures would be reported upon completion of their analyses at study completion.

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 Response-Evaluable analysis set includes all participants with measurable disease who meet the following 3 criteria: (1) had a baseline disease assessment, (2) received study treatment, and (3) had post-baseline disease assessment or discontinued treatment due to documented disease progression or clinical progression.

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 Full Analysis Set (FAS) included all participants who were enrolled in the study and received any amount of study treatment.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Confirmed Objective Response Rate (cORR) as Assessed by Investigator, measured over From the first dose of study treatment until the first documented CR or PR on or before the first documented PD or new anti-cancer therapies or death, whichever occurred first (up to 28.3 months).

The primary endpoint is confirmed objective response rate, expressed as the percentage of participants with a best overall response of complete response or partial response. Investigators assess response according to RECIST v1.1. A response is considered confirmed when the subsequent response assessment occurs at least 4 weeks after the initial response.

Under the stated criteria, complete response means disappearance of all target lesions, with pathological lymph nodes reduced to a short axis <10 mm. Partial response requires at least a 30% decrease in the sum of target-lesion diameters from baseline. The description also defines progressive disease as at least a 20% relative increase in that sum, using the smallest sum recorded on study as the reference.

As a general statistical point, response rate is a binary outcome at the participant level: each participant either meets the confirmed-response definition or does not. A percentage gives the observed frequency in the analysis population, while a confidence interval conveys uncertainty around that estimate. In a single-group study, this endpoint describes responses observed among treated participants; by itself, it does not estimate a comparative treatment effect against a control group.

The assessment timeframe runs from the first dose until the first documented complete or partial response on or before documented progression, new anticancer therapy, or death, whichever occurs first, up to 28.3 months. The response-rate estimate and its 90% confidence interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary outcome is a proportion: the percentage of participants in the response-evaluable analysis set who have a confirmed complete or partial response. The registry identifies a 90% confidence interval as the measure of uncertainty. No response estimate or interval bounds are reported in the registry record, and the statistical method used to calculate that interval is not reported in the registry record.

What does a response proportion represent?

As a general statistical explanation, a binary outcome classifies each participant according to whether a specified event occurred. For this endpoint, the event is a confirmed objective response under the stated criteria. The proportion is the number meeting the response definition relative to the analysis population. Its interpretation depends on the endpoint rules, the population included, and the completeness of outcome assessment. Enrollment alone does not give the denominator for this endpoint, because the response-evaluable population has additional disease-measurement and follow-up requirements.

The endpoint uses investigator-assessed RECIST v1.1 criteria. Complete response requires disappearance of target lesions and reduction of pathological lymph nodes to a short axis <10 mm. Partial response requires at least a 30% reduction in the sum of target-lesion diameters from baseline. The record calls a response confirmed when a subsequent response assessment is at least 4 weeks after the initial response. These definitions specify how observations become the binary endpoint; they do not report how many participants satisfied it.

How should the confidence interval be read?

In general, a confidence interval is a range expressing uncertainty around an estimated quantity under a statistical procedure. A narrower interval usually indicates greater precision than a wider interval, but precision is not the same as clinical importance, and an interval does not remove limitations of study design or measurement. Here, the interval level is 90%. Its numerical limits, calculation method, and any assumptions used for the calculation are not reported in the registry record. No conclusion about precision can be drawn without those limits and the response estimate.

A confidence interval around a single-group percentage describes uncertainty in that group’s response proportion. It does not create a control group or provide a randomized treatment contrast. General statistical reasoning distinguishes estimation from comparison: estimating a response frequency answers how often the defined outcome was observed in the analyzed group, while a comparative effect requires a suitable comparator and an analysis designed for that contrast. This study’s registry record lists a single-group model and no comparator arm.

What role does the basket design play?

A basket study evaluates a treatment across more than one disease category under a shared biological feature or treatment rationale. This registry lists several tumor categories and nine cohorts in its safety information. The number of participants and response results in each cohort are not reported in the registry record. When populations differ by tumor type or by regimen, an aggregate summary may not convey the outcomes of each subgroup. The registry record does not describe a statistical model that pools cohorts or adjusts for differences between them.

Participants with hormone-receptor-positive HER2-mutant breast cancer receive fulvestrant in addition to tucatinib and trastuzumab. This regimen distinction means that outcomes for that subgroup would represent a combination with an additional agent. The posted information does not report subgroup efficacy estimates or a method for separating the contribution of each drug. Because there is no control group, the registry design does not isolate the effect of any individual component.

What is over-dispersion, and is it relevant?

As a general concept, over-dispersion occurs when variation in observed data is greater than expected under a simple statistical model. It can matter when a model assumes a particular degree of variability, because underestimated variation can make uncertainty appear smaller than it is. The registry record does not report a model for the primary outcome or identify over-dispersion as an issue. It is therefore not possible to determine whether it was assessed or how it might affect the analysis.

The registry describes the endpoint timeframe as beginning at first dose and ending at specified disease or treatment events, or death, whichever occurs first, with follow-up up to 28.3 months. The precise timing and frequency of assessments, the rules for censoring or handling treatment changes, and the approach to missing assessments are not reported in the registry record. These choices can affect which response assessments are available and how participants are classified.

Separate from the trial’s outcome analysis, a planning illustration may express participants per arm for a chosen power target under stated assumptions. Such an illustration is not an observed study result or a retrospective measure of power. The stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects expressed as fractions of the observed effect. The illustration is not the trial’s own design: this study is single-group, and its sample-size justification is not reported in the registry record. No planning illustration can turn the study into a randomized comparison or replace the missing primary endpoint estimate.

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("Tucatinib+Trastuzumab (Cohort 1)", "Tucatinib+Trastuzumab (Cohort 2)", "Tucatinib+Trastuzumab (Cohort 3)", "Tucatinib+Trastuzumab (Cohort 4)", "Tucatinib+Trastuzumab (Cohort 5)", "Tucatinib+Trastuzumab (Cohort 6)")
n      <- c(11, 30, 30, 25, 12, 31)
events <- c(3, 4, 14, 2, 1, 7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Tucatinib+Trastuzumab (Cohort 1)  11  3  27.3  6.0  61.0  9.7  56.6  9.9  57.2
ARM  Tucatinib+Trastuzumab (Cohort 2)  30  4  13.3  3.8  30.7  5.3  29.7  5.5  29.8
ARM  Tucatinib+Trastuzumab (Cohort 3)  30  14  46.7  28.3  65.7  30.2  63.9  30.2  64.0
ARM  Tucatinib+Trastuzumab (Cohort 4)  25  2  8.0  1.0  26.0  2.2  25.0  2.4  25.1
ARM  Tucatinib+Trastuzumab (Cohort 5)  12  1  8.3  0.2  38.5  1.5  35.4  1.9  36.0
ARM  Tucatinib+Trastuzumab (Cohort 6)  31  7  22.6  9.6  41.1  11.4  39.8  11.5  40.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures. In addition to confirmed objective response rate, the secondary outcomes include investigator-assessed disease control rate, duration of response, and progression-free survival; overall survival; and measures of treatment-emergent adverse events, laboratory abnormalities, dose modifications due to adverse events, and adverse events of special interest. The record contains no analysis records. Numerical results and detailed analysis plans for these outcomes are not reported in the registry record.

When several outcomes or subgroup analyses are examined, the chance of finding an apparently notable result can increase. As a general statistical principle, multiplicity methods can address this issue by specifying which comparisons are primary and how error rates are controlled. Whether the study prespecified a hierarchy of outcomes, adjusted for multiple testing, or planned particular subgroup analyses is not reported in the registry record. The number of outcomes alone does not show which were formally tested or how their results should be interpreted.

The primary analysis set is described as participants with measurable disease who had baseline assessment, received study treatment, and had either a post-baseline disease assessment or discontinued because of documented progression. The available population wording is incomplete, so the full analysis-population rule is not reported in the registry record. The number included in this set is also not reported.

Missing-data methods are not reported in the registry record. In general, missing assessments can affect endpoint classification when response depends on measurements over time. Relevant details would include how participants without post-baseline measurements were handled, whether treatment discontinuation affected inclusion, and how incomplete confirmation was treated. The record’s response definition and population description provide some criteria, but not a full account of missing-data handling. Sample-size justification, interim analyses, and the detailed statistical analysis plan are not reported in the registry record.

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: acute kidney injury (12.0%), abdominal pain (9.1%), constipation (9.1%), enteritis (9.1%), intestinal obstruction (9.1%).

The safety information is arranged by cohort and distinguishes participants at risk from participants affected for serious and other adverse events. For serious events, the listed at-risk and affected counts are: cohort 1, 11 and 5; cohort 2, 31 and 11; cohort 3, 30 and 13; cohort 4, 25 and 9; cohort 5, 12 and 2; cohort 6, 31 and 9; cohort 7, 13 and 7; cohort 8, 31 and 8; and cohort 9, 33 and 14. For other events, the corresponding counts are: cohort 1, 11 and 10; cohort 2, 31 and 30; cohort 3, 30 and 29; cohort 4, 25 and 23; cohort 5, 12 and 12; cohort 6, 31 and 29; cohort 7, 13 and 13; cohort 8, 31 and 31; and cohort 9, 33 and 30.

The record also lists deaths by cohort: 9, 22, 22, 17, 6, 21, 10, 11, and 25, respectively. The listed serious-event terms with percentages are acute kidney injury, 12.0%; abdominal pain, 9.1%; constipation, 9.1%; enteritis, 9.1%; intestinal obstruction, 9.1%; and small intestinal obstruction, 9.1%. These are descriptive registry counts and percentages. The record does not provide a comparator group or enough context to interpret them as comparative risks. Cohort sizes differ, and the available figures should not be combined into a treatment-effect estimate.

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

The primary endpoint is designed to describe confirmed tumor responses among participants who meet the response-evaluable criteria. Its definition includes investigator assessment, RECIST v1.1, and confirmation at least 4 weeks after the initial response. These rules make clear what counts as a response, but they do not establish how frequent responses were in the study.

The key interpretive limitation is that the registry record does not report a primary response estimate or its 90% confidence interval. The number of participants in the response-evaluable population is also not reported. Thus, neither the observed response proportion nor its statistical precision can be assessed from the posted information. The total enrollment of 217 should not be substituted for the endpoint-specific denominator.

Even if an estimate were available, a single-group study would show the response experience within the treated group rather than a randomized contrast. It could not, on its own, establish what would have occurred under a different treatment or separate the effects of tucatinib, trastuzumab, and the additional fulvestrant used for the specified breast-cancer subgroup. General clinical-trial interpretation requires attention to design as well as the size and precision of an estimate.

The registry also names secondary outcomes and provides cohort-level safety counts, but the outcome definitions and numerical results are incomplete for drawing broad conclusions. Descriptive safety counts do not show comparative safety in the absence of a control group, and variation in cohort size and composition complicates direct comparisons across cohorts. The information is useful for understanding the recorded study structure and what was tracked, but it does not support a conclusion about comparative benefit or harm.

Accordingly, the statistical meaning available from this record is chiefly about the question asked and the method of defining a response. Whether the observed outcomes were frequent, precisely estimated, or different across tumor groups is not reported in the registry record. Those are distinct questions that require outcome results and fuller analysis details.

14. Why This Trial Matters Statistically

This trial is statistically notable as a single-group basket study spanning several solid-tumor categories with HER2 alterations. The design raises an important estimation question: how often did participants meeting the response-evaluable criteria have a confirmed response? The registry specifies an endpoint intended to answer that question, but does not report the estimate or its 90% confidence interval. The distinction between having a defined endpoint and having a reported result is essential when interpreting a registry record.

The response criteria also show how clinical measurements become a statistical outcome. RECIST v1.1 thresholds and the confirmation requirement classify each participant’s response status. A clear rule promotes consistent classification, while the analysis population and assessment completeness determine which participants contribute information. The registry record describes some population criteria but leaves the wording incomplete and does not report the analysis-set size or missing-data approach.

The basket structure makes pooled interpretation especially important to scrutinize. Participants come from different tumor categories, and the specified breast-cancer subgroup receives an additional drug. An overall summary would not automatically represent every disease subgroup or regimen. Cohort-specific efficacy estimates and details of any pooling strategy are not reported in the registry record.

Finally, this record illustrates why design governs what a statistical result could mean. With a single treated group, a response proportion can describe observed responses, but it cannot provide a randomized treatment contrast. The posted safety counts are descriptive as well. The registry record’s value for statistical reading is therefore in clarifying the endpoint, study structure, and limits of inference, while leaving the central outcome result unreported.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The most consequential limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. Neither the response percentage, its 90% confidence interval, nor the response-evaluable denominator is available in the recorded details. Without these, the magnitude and precision of the endpoint cannot be described.

The single-group design has no concurrent control. Any observed response frequency would describe participants receiving the study regimen, not a randomized difference against another treatment. The regimen is also not identical for every participant because fulvestrant is added for hormone-receptor-positive HER2-mutant breast cancer. The registry does not report efficacy estimates by cohort or subgroup, or a method to distinguish effects of the regimen’s components.

The study spans multiple tumor categories, but the distribution of participants among those categories and the cohort-specific outcome results are not reported in the registry record. The total enrollment of 217 therefore does not establish the amount of information available for any particular tumor group. The description of the response-evaluable population is truncated, and its final eligibility wording is incomplete.

Other important analysis details are not reported in the registry record, including the statistical analysis plan, sample-size justification, missing-data rules, multiplicity strategy, and interim-analysis plans. The registry lists secondary outcomes but does not provide numerical results for them in the registry record for this analysis. The safety figures are descriptive and do not support a controlled comparison. These limitations constrain conclusions to the design and stated endpoint definitions rather than outcome effectiveness or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Basket Study of Tucatinib and Trastuzumab in Solid Tumors With HER2 Alterations — NCT04579380.
• Registry record last updated 2026-08-21; status last verified 2026-08.
• Results first posted 2024-11-13.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04579380 is a phase 2, single-group basket study of tucatinib plus trastuzumab for previously treated, locally advanced unresectable or metastatic solid tumors driven by HER2 alterations. Fulvestrant is added for hormone-receptor-positive HER2-mutant breast cancer. The registry lists enrollment of 217, status active, not recruiting, a start date of 2021-01-11, and a primary completion date of 2023-11-01.

The primary endpoint is investigator-assessed confirmed objective response rate under RECIST v1.1, with a stated 90% confidence interval and a timeframe up to 28.3 months. The response result, interval limits, and analysis-set size are not reported in the registry record. Secondary outcomes cover disease control, response duration, progression-free and overall survival, and several safety measures. The record lists nine cohorts for safety information, but the single-group design does not provide a randomized comparator. Analysis-plan details and the full response-population wording are not reported in the registry record.