Testing Palbociclib (PD-0332991) as Potentially Targeting Treatment in Cancers With CDK4 or CDK6 Amplification (MATCH - Subprotocol Z1C): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing Palbociclib (PD-0332991) as Potentially Targeting Treatment in Cancers With CDK4 or CDK6 Amplification (MATCH - Subprotocol Z1C) (NCT06390839), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The study is MATCH Treatment Subprotocol Z1C, a phase II investigation of palbociclib in tumors with CDK4 or CDK6 amplification. Its brief summary describes palbociclib as a kinase inhibitor intended to block signaling associated with the amplified genes. That rationale explains the treatment selection, but it is not itself evidence of a clinical response.

The registry lists advanced and refractory lymphoma and malignant solid neoplasm among the conditions. The response definition draws on different tumor assessment standards: RECIST version 1.1, the Cheson (2014) criteria for lymphoma, and Response Assessment in Neuro-Oncology criteria for glioblastoma. Thus, the clinical question is whether a participant meets the applicable complete- or partial-response definition, rather than whether every cancer type is judged by one identical measurement rule.

The listed enrollment is 43. The primary endpoint population is described as eligible, treated participants with mutation status confirmed, while the endpoint definition refers to analyzable patients. The registry record does not report how many participants contributed to the primary endpoint or how the analysis population was determined.

3. Trial Design

This is a phase II, single-group treatment study. The registry identifies the intervention arm as treatment with palbociclib and gives allocation as not applicable and masking as none. There is no randomized control arm, so the design is intended to describe outcomes within the treated group rather than estimate a randomized treatment difference.

Participants receive palbociclib by mouth once daily on days 1–21 of each 28-day cycle. Cycles repeat while there is no disease progression or unacceptable toxicity. The listed trial procedures include biopsy, biospecimen collection, computed tomography and magnetic resonance imaging. The arm description says CT or MRI and blood sample collection occur during the trial, and participants may also undergo biopsy.

Tumor assessments are scheduled at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration. This schedule supplies the context for measuring response over time; it does not mean that every participant necessarily completes every scheduled assessment.

The registry lists enrollment of 43, a start date of 2017-03-22 and primary completion on 2022-01-15. The study status is active, not recruiting. The sponsor is the National Cancer Institute (NCI). These record details describe the study setting and progress, but do not establish the number included in the primary endpoint analysis.

The primary endpoint is objective response rate. The listed secondary outcomes are 6-month progression-free survival rate and progression-free survival. The registry record lists three outcome measures and zero analyses. It does not report a treatment comparison, an analysis plan, or numerical results for the primary or secondary outcomes. The absence of a control arm also means that any observed outcomes in the treated group would not, on their own, isolate the effect of palbociclib from other explanations.

Although planning illustrations may use a two-arm framework, that convention does not alter the actual design: the study is single-group and is not a randomized comparison. Such illustrations are planning exercises, not observed power and not evidence that a control group was enrolled.

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: Out of the 43 patients, 16 patients were enrolled on the basis of the results from the NCI-MATCH assay and 27 on the basis of the outside assay results. Twelve of the 27 outside lab patients had their samples centrally confirmed.

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 (ORR), measured over Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration.

The primary endpoint is objective response rate, defined as the percentage of analyzable patients whose tumors have a complete or partial response to treatment. Response is classified using RECIST version 1.1, the Cheson (2014) criteria for lymphoma patients, and Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The registry record says further details about complete and partial response are in the master protocol; those details are not reported in the registry record.

In general, an objective response endpoint turns tumor assessment into a binary outcome for each analyzable participant: a participant either meets the specified response definition or does not. The percentage provides a concise description of how often a response was observed in the defined analysis population. It is useful in a phase II setting because it focuses on documented tumor change rather than relying only on treatment exposure or biological rationale.

Interpretation depends on the denominator and the assessment rules. Here, the record specifies eligible, treated participants with mutation status confirmed as the primary population, but the endpoint definition also uses the term analyzable patients. The number analyzed and any rules for handling participants without an evaluable assessment are not reported in the registry record.

The registry states that a two-sided exact binomial 90% confidence interval is calculated for the response rate. In general, a confidence interval describes uncertainty around an estimated percentage under the model used. However, neither the response estimate nor its interval is reported in the registry record. The endpoint definition and planned interval therefore cannot be used to infer how many participants responded or how precise the result was.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It defines the primary endpoint and says a two-sided exact binomial confidence interval is calculated, but it does not report a primary analysis, its numerical result, or a full statistical analysis plan. The concepts below explain the stated method in general; they do not fill in missing trial procedures.

What does a response percentage represent?

In general, a binary endpoint assigns each participant to one of two categories under a specified definition. For objective response, the categories are whether an analyzable participant meets the complete- or partial-response criteria. The response rate is the proportion of participants classified as having a response within the analysis population. Because the denominator matters, an enrollment count cannot automatically be substituted for the number analyzed.

For this study, response criteria differ by tumor type: RECIST version 1.1, the Cheson (2014) criteria for lymphoma, and Response Assessment in Neuro-Oncology criteria for glioblastoma. In general, predefined criteria help make outcome classification more consistent. The registry record does not report the full protocol definitions, reviewer procedures, or tumor-specific response results.

Why use a binomial confidence interval?

In general, a binomial model is used for a proportion formed from participant-level outcomes classified as event or no event. An exact binomial confidence interval is a method for describing uncertainty around the estimated proportion without relying on a normal approximation to the sampling distribution. A two-sided interval gives lower and upper bounds around the estimate. The stated confidence level is 90%.

A confidence interval is not a guarantee that the true response rate lies within a particular range, and it is not a measure of the probability that an individual participant will respond. It conveys statistical uncertainty under the model and analysis population used. The interval’s width depends in part on the number of evaluable participants and the observed proportion. The registry record reports neither the response estimate nor its interval, so their width and implications cannot be assessed.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed among its treated participants. Without a concurrent control group, it cannot directly estimate a randomized difference between palbociclib and another treatment. Other influences, such as participant characteristics, tumor course and assessment practices, are not separated from treatment exposure by random assignment in this design. This is a design limitation, not a finding about the treatment.

The registry lists allocation as not applicable, masking as none, and the model as single group. These details support reading the study as a treated cohort rather than a controlled comparison. No adjustment strategy or model for the primary endpoint is reported in the registry record.

How should planning illustrations be understood?

General sample-size illustrations are planning exercises. The stated assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of an observed effect. Those assumptions describe the illustration, not the actual single-group design or a trial-specific design justification. The registry record does not report the trial’s sample-size justification.

Planning quantities such as participants per arm for a chosen power are not observed power. They do not indicate the probability that this completed or ongoing study detected an effect, and they do not supply a missing result. A two-arm planning framework should not be mistaken for evidence that the study enrolled two arms. Here the registry design is single group, and the record explicitly does not support a like-for-like control comparison.

In general, over-dispersion occurs when observed variation exceeds what a chosen statistical model expects. It can make standard errors and confidence intervals based on that model too optimistic if not addressed. The registry record does not state that over-dispersion was assessed or that it was relevant to this primary binary endpoint. No such analysis should be inferred from the endpoint definition alone.

What remains unavailable?

The record lists zero analyses. It does not report the response count, endpoint denominator, response estimate, confidence interval, missing-data approach, sensitivity analyses, subgroup analyses, or statistical software and model details. It also does not state whether there were interim analyses or how any were handled. These are not details that can be reconstructed from the stated endpoint and confidence-interval method.

The listed secondary outcomes are 6-month progression-free survival rate and progression-free survival. In general, time-to-event outcomes account for the timing of an event and may also require rules for censoring participants who have not experienced an event by the end of observation. The registry record does not describe its time-to-event analysis, censoring rules, or numerical results. Neither those outcomes nor the primary response endpoint can be independently evaluated from the methods description alone.

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 (Palbociclib)")
n      <- c(25)
events <- c(1)
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 (Palbociclib)  25  1  4.0  0.1  20.4  0.7  19.5  0.9  19.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists objective response rate as the primary outcome and 6-month progression-free survival rate and progression-free survival as secondary outcomes. It does not report a multiplicity strategy, such as an adjustment to account for assessing more than one outcome. The record also does not specify a hierarchy among the secondary outcomes or explain how confirmatory claims would be controlled. Those procedures are not reported in the registry record.

The registry gives a primary population of eligible, treated participants with mutation status confirmed, while the endpoint definition refers to analyzable patients. It does not report the count in either analysis population, how eligibility and treatment exposure were applied to the endpoint analysis, or how participants without an evaluable response assessment were handled. A missing-data method, imputation procedure, or sensitivity analysis is not reported in the registry record.

These distinctions affect interpretation. In general, excluding participants without an evaluable endpoint can make the analyzed population differ from the enrolled population. The direction and size of any resulting bias depend on why data are missing and how participants are handled. Without the number and reasons for missing assessments or the analysis rules, that possibility cannot be evaluated for this study.

The record lists enrollment of 43, but does not report the primary outcome denominator. It also lists three outcome measures and zero analyses. Thus, the endpoint definitions are available, while the analysis populations, missing-data handling and multiplicity procedures are not reported in the registry record. No assumptions about these procedures should be treated as the study’s statistical plan.

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: neutrophil count decreased (35.0%), white blood cell decreased (25.0%), lymphocyte count decreased (20.0%), platelet count decreased (5.0%), anemia (2.5%).

The palbociclib treatment group lists 40 participants at risk for serious adverse events and 40 at risk for other adverse events. The record lists 22 participants affected by serious adverse events and 30 affected by other adverse events. These are group-level safety entries, distinct from the primary objective response endpoint.

The serious adverse event terms with the largest listed percentages are neutrophil count decreased, 35.0%; white blood cell decreased, 25.0%; lymphocyte count decreased, 20.0%; platelet count decreased, 5.0%; anemia, 2.5%; and blood and lymphatic system disorders - Other, specify, 2.5%. The registry record does not clarify in this entry whether participants could contribute to more than one term, nor does it give term-specific counts. The listed percentages therefore should not be added or treated as mutually exclusive categories.

The record also lists 33 deaths. It does not provide their causes, timing, relationship to treatment, or a detailed accounting of follow-up in this safety entry. A death count alone cannot be interpreted as a treatment-attributed count. The adverse-event figures describe what is recorded for the group, but do not establish causation or make a comparison with an untreated or randomized control group.

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

The registry record establishes that a phase II, single-group study of palbociclib was conducted for participants with tumors carrying CDK4 or CDK6 amplification. It identifies objective response rate as the primary endpoint and describes how response is classified. It does not report the response rate, its confidence interval, or the number of participants analyzed for that endpoint.

Accordingly, the posted information does not show the observed frequency of complete or partial responses. It cannot establish whether the response estimate was large or small, precise or imprecise, or whether it met a benchmark. The absence of a reported analysis is not evidence that no responses occurred; it means the registry record does not report the result.

Even if a response percentage were available, this single-group design would describe outcomes in the treated participants rather than provide a randomized comparison. In general, an observed outcome in one group cannot by itself determine what would have happened to comparable participants under another treatment or no study treatment. The study’s biological rationale and endpoint definition do not substitute for a control group or a reported outcome analysis.

The listed secondary outcomes and safety entries should also be kept distinct. Progression-free survival outcomes are named but have no posted numerical analyses. Safety information includes adverse event counts, selected serious-event percentages and a death count, but does not establish causation. Each type of information answers a different question, and none can be used to fill in the missing primary response result.

The most defensible conclusion from the registry record is therefore limited: it describes the study design, treatment schedule, response endpoint and some safety entries, but does not report the primary efficacy analysis. Any claim about the magnitude, precision or comparative effect of palbociclib would go beyond the information recorded.

14. Why This Trial Matters Statistically

This study raises a useful statistical question about biomarker-selected treatment: how should a response endpoint be interpreted when participants are selected for a particular genetic feature and receive treatment in a single group? The registry identifies CDK4 or CDK6 amplification as the treatment-selection context and objective response rate as the primary endpoint. That pairing makes the analysis population and the response definition central to understanding any eventual estimate.

It also illustrates why a stated endpoint is not the same as a reported result. The record specifies a response definition and an exact binomial confidence interval, yet lists zero analyses and provides no estimate. Without the result, readers cannot judge either the observed response frequency or its statistical precision. This distinction is important when reading registry records: methods can be described even when outcome values are absent.

The design further clarifies the difference between estimating an outcome within a cohort and estimating a treatment contrast. A single-group phase II study can be designed to describe response among treated participants, but it does not create a randomized comparison. A planning illustration based on two arms does not change that design or yield observed power.

Finally, the record emphasizes the role of analysis populations and missing assessments. Enrollment is listed, but the number analyzed for the primary endpoint and the handling of participants without evaluable response are not. In general, those details are needed to interpret a percentage and its uncertainty. The missing information limits the statistical conclusions that can be drawn, regardless of the clinical rationale for studying the biomarker-selected group.

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 this trial from the registry record is the absence of the primary endpoint result. The record gives no response count, response percentage, confidence interval, or analysis denominator. Although it states that a two-sided exact binomial 90% confidence interval is calculated, the estimate and interval are not reported in the registry record.

The single-group design has no concurrent comparator, so the study cannot provide a randomized contrast. This limits what could be inferred about differences relative to another treatment, even if the response estimate were available. The registry also lists no masking.

The listed enrollment is 43, while 40 participants are listed at risk in the treatment group for adverse-event reporting. The registry record does not explain the difference or give the primary endpoint analysis population size. These counts relate to different record entries and should not be assumed to have identical denominators.

Response assessments use criteria that vary across tumor types. The registry does not provide the tumor-type distribution, tumor-specific endpoint results, full response definitions from the master protocol, or details of assessment review. It also does not report missing-assessment rules, censoring methods for progression-free survival, multiplicity procedures, interim analyses, or a trial-specific sample-size justification.

Finally, the safety entry lists serious and other adverse-event counts, selected serious-event percentages and deaths, but does not provide enough detail to determine event timing, attribution or causes of death. These limitations restrict both efficacy and safety interpretation from the registry record; they do not imply a particular unreported outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing Palbociclib (PD-0332991) as Potentially Targeting Treatment in Cancers With CDK4 or CDK6 Amplification (MATCH - Subprotocol Z1C) — NCT06390839.
• Registry record last updated 2026-07-17; status last verified 2026-07.
• Results first posted 2024-12-10.
• 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

NCT06390839 is MATCH Treatment Subprotocol Z1C, a phase II single-group study sponsored by the National Cancer Institute (NCI). It evaluates palbociclib in participants with tumors with CDK4 or CDK6 amplification. The registry lists enrollment of 43, a study start date of 2017-03-22, primary completion on 2022-01-15, and status active, not recruiting.

Participants receive palbociclib by mouth on days 1–21 of each 28-day cycle, with treatment continuing in the absence of progression or unacceptable toxicity. Objective response rate is the primary endpoint; progression-free survival and 6-month progression-free survival rate are secondary outcomes.

The registry describes the response criteria and states that a two-sided exact binomial 90% confidence interval is calculated. It lists zero analyses and does not report the primary response estimate or interval. Safety entries include 40 participants at risk, 22 affected by serious adverse events, 30 affected by other adverse events, 33 deaths, and selected serious-event terms with percentages.