Testing Trastuzumab and Pertuzumab in Patients With Higher Than Normal Copies of the HER2 Gene Found in Their Tumors (MATCH - Subprotocol J): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing Trastuzumab and Pertuzumab in Patients With Higher Than Normal Copies of the HER2 Gene Found in Their Tumors (MATCH - Subprotocol J) (NCT06136897), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

3. Trial Design

This is a phase II, single-group treatment study within the MATCH program. The registry lists trastuzumab plus pertuzumab as the treatment and does not identify a comparator arm. Allocation is not applicable, and masking is listed as none. These design features mean the primary question is about response among treated participants, not a randomized comparison of treatment strategies.

The registry lists an enrollment of 35. This is the recorded enrollment figure; it is not, by itself, a statement of how many participants were included in the primary endpoint analysis. The primary endpoint population is described separately as eligible, treated, and mutation status confirmed. The number meeting that analysis-population definition is not reported in the registry record.

The trial start date is 2017-03-23, and primary completion is recorded as 2021-11-03. Its status is active, not recruiting. The intervention description specifies intravenous pertuzumab over 30-60 minutes and trastuzumab over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Trial procedures include biopsy, biospecimen collection, echocardiography, and radiologic examination. Tumor assessments were scheduled at baseline and then at stated cycle intervals, with follow-up described as extending up to 3 years post registration. This timing defines when response could be assessed; it does not establish that all participants had the same duration of observation. The record does not report participant-level follow-up or the number assessed at each time point.

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: Patients with HER2 amplification as established in the analytical assay (CN ≥7) detected by NGS, were considered for the Arm J subprotocol. The mutation status was determined by an NCI-MATCH approved laboratory for 24 patients in this arm, these cases had to be confirmed to be used in primary analysis.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible, treated and mutation status confirmed

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: Patients who were eligible, started protocol therapy, and had mutation status confirmed at the analysis time were the analyzable patients

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate, measured over Tumor assessments occurred at baseline, then every 3 cycles for the first 33 cycles, and every 4 cycles thereafter until disease progression, up to 3 years post registration.

The primary endpoint is objective response rate, expressed as the percentage of participants whose tumors have a complete or partial response among analyzable patients. The population specified for this endpoint is eligible, treated participants with mutation status confirmed. Response is defined using Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and Response Assessment in Neuro-Oncology criteria for glioblastoma patients.

In general, an objective response endpoint summarizes whether tumors meet prespecified criteria for complete or partial response. It provides a defined way to describe tumor response across assessments, rather than relying on an informal impression of change. Since the trial covers multiple cancer types, the registry identifies different response criteria for particular tumor groups.

The record specifies a two-sided binomial exact 90% confidence interval for the response rate. In general, a confidence interval conveys uncertainty around an estimated rate; its width depends in part on the amount of outcome information available. However, the registry record does not report the response count, estimated rate, or interval limits, so the endpoint’s observed value and precision cannot be described from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Objective response rate is a binary-outcome summary: each analyzable participant is classified according to whether a complete or partial response was recorded under the specified criteria. The rate is the proportion classified as responders in the endpoint population. In general, this type of summary is useful when the research question concerns the share of participants meeting a defined response threshold. The registry record does not report the response count or rate for this study, so no numerical estimate can be interpreted.

The endpoint description specifies a two-sided binomial exact confidence interval at 90%. In general, a confidence interval presents a range of values compatible with the observed data under the stated statistical method. The exact binomial approach is designed for a proportion and does not rely on the same normal approximation used by some simpler interval methods. An interval’s width reflects statistical uncertainty; it is not a guarantee that the true value lies within the displayed limits. Since no interval limits are reported, the uncertainty around this trial’s response rate cannot be assessed.

The response criteria vary by tumor context. The registry names Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and Response Assessment in Neuro-Oncology criteria for glioblastoma patients. In general, prespecified criteria aim to make outcome classification more consistent by defining what counts as complete or partial response. Applying different criteria to different disease groups recognizes that response assessment is not identical across all tumor types. The registry refers to the master protocol for details on complete and partial response definitions; those detailed rules are not reported in the record.

The design is single group and unmasked, with allocation listed as not applicable. In general, a single-group study estimates outcomes within its treated population, while a randomized comparison is designed to compare outcomes between assigned groups. Without a concurrent control group, differences from other populations or historical results would not by themselves establish a treatment effect. No such comparison is reported in this registry record.

The registry lists sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect, and distinguishes participants per arm for 80% power from time-to-event event totals. These are planning illustrations, not observed power and not a description of this single-group trial’s allocation. The actual illustration values and the observed primary effect are not reported in the registry record. The record also does not report the trial’s sample-size justification or statistical design rationale.

In general, over-dispersion matters when observed variation is greater than a statistical model expects; a model that does not account for it can give misleading uncertainty estimates. The registry record does not identify an over-dispersion model for this endpoint, and the binomial exact interval description does not report a separate adjustment for it. No additional model details should be inferred.

Progression-free survival is listed as a secondary outcome, alongside the 6-month progression-free survival rate. In general, time-to-event analysis accounts for the timing of an event and can also handle participants whose event status is not observed through the full follow-up period using censoring rules. The registry record does not report the event definition, censoring rules, analysis method, estimates, or confidence intervals for these secondary outcomes. The exact time-to-event methods therefore cannot be described.

The registry lists zero analyses. It does not report hypothesis tests, model adjustments, interim analyses, or an analysis plan for the primary endpoint. These details are distinct from the outcome definition and should not be inferred from the study’s phase or treatment schedule.

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("Treatment (Pertuzumab, Trastuzumab)")
n      <- c(25)
events <- c(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  Treatment (Pertuzumab, Trastuzumab)  25  3  12.0  2.5  31.2  4.2  30.0  4.4  30.2

11. Multiplicity, Missing Data and Analysis Populations

The record lists objective response rate as the primary outcome and identifies 6-month progression-free survival rate and progression-free survival as secondary outcomes. It does not report how multiple outcomes or repeated statistical tests were handled. A multiplicity plan, including whether any adjustment was intended, is not reported in the registry record. No inference should be made about a family-wise error rate or the confirmatory status of secondary outcomes.

Missing-data handling for the primary endpoint is not reported in the registry record. The endpoint is defined among analyzable patients, but the record does not state how participants without an evaluable tumor assessment were treated in the analysis, or how missing response assessments were classified. The number of participants included in the primary analysis is also not reported. These omissions matter because the analyzed population and handling of unavailable outcomes affect the interpretation of a response percentage.

The record names the primary population as eligible, treated, and mutation status confirmed. It does not provide a flow of participants through eligibility, treatment, mutation confirmation, and endpoint assessment. Although the enrollment figure is 35, it should not be treated as the primary analysis denominator without a reported accounting of the endpoint population.

Interim analyses, stopping rules, and other prespecified analysis details are not reported in the registry record. The record’s status and completion dates do not establish whether interim monitoring occurred. The absence of these details limits assessment of how the analyses were planned and how the outcome population was formed.

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: heart failure (5.7%), fatigue (2.9%), infusion related reaction (2.9%), abdominal pain (2.9%), hepatobiliary disorders - other, specify (2.9%).

The adverse-event record lists 9 participants affected by serious adverse events among 35 at risk and 27 affected by other adverse events among 35 at risk. These are separate registry counts; the record does not explain overlap between categories or provide event-level timing. The serious adverse event terms with listed percentages include heart failure at 5.7%, fatigue at 2.9%, infusion related reaction at 2.9%, abdominal pain at 2.9%, hepatobiliary disorders - Other, specify at 2.9%, and alkaline phosphatase increased at 2.9%.

The record also lists 27 deaths. It does not establish whether those deaths occurred during treatment, whether they were attributed to the study drugs, or how they relate to the serious and other adverse-event counts. The counts should therefore be read as registry safety figures, not as evidence that treatment caused an event. The record does not provide a control group for comparing these figures with another treatment strategy, nor does it report additional context such as event timing or attribution.

In general, adverse-event counts describe events recorded under a study’s reporting definitions. They do not, by themselves, establish causation. The registry record does not report enough detail to determine causal attribution or to interpret the death count beyond its listing.

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

This trial is a single-group phase II study of trastuzumab plus pertuzumab in patients with specified HER2-amplified cancers outside the breast, gastric or gastroesophageal junction, and colorectal groups. Its primary endpoint is objective response rate among eligible, treated participants with confirmed mutation status. The registry supplies the response definition and assessment schedule, but not the result.

As a result, the record does not establish how many participants had a complete or partial response, what proportion responded, or how precisely that proportion was estimated. It also does not report estimates for the listed progression-free survival outcomes. The trial’s enrollment figure cannot be substituted for the unknown primary analysis population.

Even if a response result were available, a single-group design would describe outcomes in the treated population rather than provide a randomized estimate of how treatment compares with a control. The design does not support attributing all observed outcomes to treatment without further evidence. The registry record does not report a comparative treatment effect.

The safety figures should also be interpreted descriptively. The record lists serious and other adverse-event counts, selected serious-event terms with percentages, and a death count, but does not report causal attribution or enough context to connect the death count with treatment exposure. These entries do not establish that treatment caused the events.

The central statistical conclusion is therefore about what can be evaluated from the record: the study question and endpoint are specified, while the primary outcome result and its uncertainty are not reported. No claim about treatment benefit, lack of benefit, or comparative safety follows from the information recorded.

14. Why This Trial Matters Statistically

This study raises a statistical question about response in a selected group of cancers that share HER2 amplification but are outside the breast, gastric or gastroesophageal junction, and colorectal groups. The endpoint uses tumor response criteria that vary by disease context, making clear outcome definitions important when a trial includes different cancer types.

The design also illustrates the distinction between describing outcomes and estimating comparative effects. A single-group study can report the proportion of its analyzable participants who meet an endpoint, but without a control group it cannot make a randomized comparison. This matters when interpreting any observed rate: a descriptive estimate and a causal treatment effect answer different questions.

Precision is another essential part of an outcome report. The registry specifies an exact binomial confidence interval for objective response, but does not give the response estimate or interval limits. Without those results, neither the observed rate nor its statistical uncertainty can be assessed. A clear endpoint definition is valuable, but it does not replace reporting the numerator, denominator, and estimate.

The record also distinguishes enrollment from the endpoint population. It lists an enrollment of 35 but defines the primary endpoint population by eligibility, treatment, and confirmed mutation status. Reporting how participants move from enrollment to analysis is necessary for readers to understand which observations contribute to the estimate.

Finally, the listed safety figures underline the need for context. Counts and event terms are informative descriptions, but they do not by themselves identify cause or permit comparison. Clear reporting of analysis populations, outcome estimates, uncertainty, missing-data handling, and event attribution is needed for a complete statistical interpretation.

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 primary limitation for interpretation is that the registry record does not report the objective response result. There is no response count, percentage, or confidence interval, despite a detailed endpoint definition. The analyzable population size is also not reported, so the endpoint denominator cannot be verified from the record.

The single-group design has no concurrent control arm. Consequently, the registry record does not provide a randomized comparison with another treatment or with a control condition. This limits interpretation to outcomes in the treated group and prevents a direct comparative estimate from this study design.

The study includes non-breast, non-gastric or gastroesophageal junction, and non-colorectal cancers, and the endpoint description identifies different response criteria for lymphoma and glioblastoma. The record does not report the composition of the analyzed cancer groups or response results by tumor type. It is therefore not possible to assess how results varied across disease groups.

Missing-data rules, the handling of participants without evaluable assessments, interim analyses, and the multiplicity plan are not reported in the registry record. The listed progression-free survival outcomes also lack reported estimates and analysis details. For safety, event attribution and the context of the listed death count are not reported. These gaps limit interpretation beyond the descriptive registry entries.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing Trastuzumab and Pertuzumab in Patients With Higher Than Normal Copies of the HER2 Gene Found in Their Tumors (MATCH - Subprotocol J) — NCT06136897.
• Registry record last updated 2026-07-30; status last verified 2026-05.
• Results first posted 2024-06-25.
• 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

The registry record describes MATCH Treatment Subprotocol J, a phase II single-group study of trastuzumab and pertuzumab for HER2-amplified non-breast, non-gastric or gastroesophageal junction, and non-colorectal cancers. The listed enrollment is 35. The trial start date is 2017-03-23, primary completion is 2021-11-03, and status is active, not recruiting.

The primary outcome is objective response rate among eligible, treated participants with confirmed mutation status, assessed using tumor-specific response criteria. The registry record does not report the response estimate or confidence interval. Secondary outcomes list 6-month progression-free survival rate and progression-free survival, with no analyses reported. Safety entries list serious and other adverse-event counts and a death count, without reported causal attribution.