Testing Ipatasertib as Potentially Targeted Treatment in Cancers With AKT Genetic Changes (MATCH - Subprotocol Z1K): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing Ipatasertib as Potentially Targeted Treatment in Cancers With AKT Genetic Changes (MATCH - Subprotocol Z1K) (NCT06400251), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

This is a phase II treatment subprotocol within MATCH, focused on tumors with AKT mutations. Its central statistical question is descriptive: among the eligible, treated participants with mutation status confirmed who could be analyzed, how often was an objective response recorded? The endpoint combines complete and partial responses, using RECIST version 1.1, the Cheson (2014) criteria for lymphoma, and Response Assessment in Neuro-Oncology criteria for glioblastoma.

The registry record reports planned enrollment of 35 and lists several cancer types, but it does not report how many participants were ultimately included in the primary analysis. It also does not report the number with complete response, partial response, or no objective response. Consequently, the clinical question is clear, but the posted information does not give the numerical response result needed to answer it.

3. Trial Design

This is a phase II, single-group study of ipatasertib in the MATCH treatment subprotocol Z1K. The registry record lists the National Cancer Institute as sponsor, planned enrollment of 35, and an active-not-recruiting status. The recorded study start is 2019-08-08, and the primary completion date is 2023-06-27. These dates describe the registry record and do not establish when every participant completed treatment or follow-up.

All participants in the treatment group received ipatasertib 400 mg by mouth once daily on days 1–28 of each 28-day cycle. The description states that cycles repeat in the absence of disease progression or unacceptable toxicity. CT or MRI is specified during screening and on study, and during follow-up as clinically necessary. The intervention list also includes biopsy and biospecimen collection procedures.

The design has no randomized allocation, comparator group, or masking. Accordingly, the trial can describe outcomes observed in participants receiving the study treatment, but its design does not support a randomized estimate of how outcomes differ from those under another treatment. The record lists progression-free survival and 6-month progression-free survival as secondary outcomes, in addition to the primary objective response rate.

Planned enrollment is not the same as the number analyzed for an endpoint. The primary endpoint population is described as eligible, treated participants with mutation status confirmed, but the number meeting that description is not reported in the registry record. The record also does not report a statistical analysis plan, a sample-size justification, or details of interim analyses. Those features should not be inferred from the phase designation or from the planned enrollment.

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 tumors harboring E17K mutations in AKT1, 2, and 3, as well as Q79K and L52R mutations in AKT1, were eligible for sub-protocol Z1K. The mutation status was determined by an NCI-MATCH approved laboratory for all patients in this arm, they had to be confirmed by the NCI-MATCH central assay to be included 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 (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 criteria depend on tumor type: the record specifies RECIST version 1.1, the Cheson (2014) criteria for lymphoma patients, and Response Assessment in Neuro-Oncology criteria for glioblastoma patients. It refers to the master protocol for details on defining complete and partial response.

Objective response is used to summarize whether measurable tumor shrinkage meeting predefined criteria occurred during assessment. A percentage is useful because it describes the proportion of the endpoint population with a qualifying response, rather than the amount of change for a single participant. It does not, by itself, describe how long a response lasts or how long participants remain free of progression.

Tumor assessments were 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. The endpoint description specifies a two-sided 90% binomial exact confidence interval for the response rate. A confidence interval expresses uncertainty around an estimated response percentage; its width depends in part on how many participants contribute to the analysis and how the responses are distributed.

The registry record does not report the response count, response percentage, or confidence limits. Thus, the endpoint definition and assessment schedule are reported, but the primary numerical result is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods that can be described are those attached to the endpoint definition and the posted design. The primary endpoint is a proportion, with an exact binomial confidence interval specified. The registry record does not report an analysis plan or the numerical endpoint result, so interpretation must distinguish the method named in the record from analyses that cannot be confirmed.

What does a response percentage represent?

A response percentage is the number of analyzed participants meeting the response definition relative to the number in the endpoint analysis population, expressed as a proportion or percentage. In this trial, the endpoint description defines response as complete or partial response. It names eligible, treated participants with mutation status confirmed as the population. The actual analysis denominator and the counts in each response category are not reported in the registry record, so the percentage cannot be reconstructed.

Response classification is based on stated criteria rather than an informal judgment that a tumor improved. The registry names RECIST version 1.1, the Cheson (2014) criteria for lymphoma, and Response Assessment in Neuro-Oncology criteria for glioblastoma. It directs readers to the master protocol for details of complete and partial response. The detailed operational rules from that protocol are not reported in the registry record.

Why use a binomial confidence interval?

For a binary endpoint, each analyzed participant is classified as having or not having an objective response under the endpoint definition. A binomial interval quantifies uncertainty around the proportion responding. The record specifies a two-sided 90% exact binomial confidence interval. “Exact” identifies a method for calculating interval limits from binomial data rather than relying on a simple normal approximation. This can be useful for proportions, particularly when the analyzed sample is not large or the proportion is near an endpoint of its possible range.

A confidence interval is not a guarantee about the true response percentage. It is a measure of statistical uncertainty under the assumptions of the method and the analyzed data. A narrower interval generally indicates more precision than a wider interval. Since the registry record does not post an estimate or interval, neither the response level nor its precision can be evaluated. The specified confidence level is not a substitute for those missing results.

How does the assessment schedule fit the endpoint?

Tumor assessments were scheduled at baseline and then every 2 cycles for the first 26 cycles, followed by every 3 cycles thereafter until disease progression, up to 3 years post registration. The schedule describes when assessments were intended to occur. It does not establish that every participant completed every planned assessment. The number with assessments at each point, the handling of missed assessments, and the response confirmation rules are not reported in the registry record.

The endpoint is a participant-level response measure, while the assessment schedule describes repeated opportunities to characterize tumor status over time. It is important not to confuse the response percentage with time-to-event outcomes. Progression-free survival and 6-month progression-free survival are listed as secondary outcomes, but their results and detailed methods are not reported in the registry record.

What does a single-group design allow?

In a single-group trial, the primary endpoint can describe the outcomes observed among participants receiving the intervention. Without a comparator group, the study does not directly estimate a difference between treatment strategies. General statistical interpretation also recognizes that an outcome observed after treatment may be affected by factors other than treatment. A randomized concurrent comparison can help address such differences; no such comparison is part of this record.

The record lists allocation as not applicable and masking as none. These details fit the single-group design but do not supply a statistical analysis plan. The record does not report whether any analysis was adjusted for participant or tumor characteristics, how any deviations were handled, or what rules determined evaluability beyond the stated endpoint population.

What can the planning information say?

Any sample-size figures associated with planning are illustrations, not observed power. The described planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. These assumptions describe a planning calculation, not the actual single-group design, which has no comparator arm. Such illustrations should not be interpreted as the trial’s own sample-size justification, an analysis of its primary result, or evidence that a particular effect was detected.

The trial’s own sample-size justification is not reported in the registry record. Planned enrollment of 35 is recorded, but that number alone does not explain how enrollment was chosen or establish the precision of the eventual response estimate. Because no primary estimate or analysis denominator is posted, an evaluation of the endpoint’s realized precision is not possible.

What cannot be inferred about the analysis?

The record reports zero analyses and does not post a primary result. It does not state whether interim analyses were planned or conducted, whether multiplicity adjustments were applied, or how missing or unevaluable tumor assessments were handled. No inferential claim should be reconstructed from the endpoint specification alone. The methods that can be stated are limited to the specified response definition, assessment timing, and exact binomial interval method; the numerical analysis and additional statistical procedures are not reported in the registry record.

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 (Ipatasertib)")
n      <- c(29)
events <- c(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  Treatment (Ipatasertib)  29  7  24.1  10.3  43.5  12.2  42.1  12.3  42.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists objective response rate as the primary outcome and lists progression-free survival and 6-month progression-free survival as secondary outcomes. It does not report a multiplicity strategy, such as whether testing across outcomes was adjusted or whether secondary outcomes were intended to be descriptive. Without that information, the relationship among any statistical tests or confidence intervals cannot be characterized.

The record does not report an analysis plan or interim-analysis details. It therefore does not establish whether additional outcomes, subgroups, or interim looks were planned, or how any such analyses would relate to the primary endpoint. These details should not be inferred from the phase II designation or the number of outcome measures.

The primary population is described as eligible, treated participants with mutation status confirmed. The number of participants meeting that definition, the number with evaluable tumor assessments, and the number included in the response analysis are not reported in the registry record. Handling of missing assessments, withdrawal, or participants who could not be classified is also not reported. These omissions matter because the endpoint is a percentage and its denominator affects both the estimate and its precision.

In general, missing outcome information can affect an estimate if participants without an observed result differ in response from those with an observed result. Statistical methods may define analysis populations or address missing data in different ways, but the registry record does not specify such methods for this endpoint. No assumptions about the missing outcomes or their likely direction are justified by the posted information.

The record’s description of the primary population and confidence-interval method is not enough to establish how every participant was handled. Until analysis details and numerical results are reported, the primary response estimate, its precision, and the interpretation of secondary outcomes remain unavailable.

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: diarrhea (8.8%), rash maculo-papular (5.9%), vomiting (5.9%), anemia (2.9%), cardiac arrest (2.9%).

The registry record lists a treatment group with 34 participants at risk for serious adverse events and 13 affected. For other adverse events, it lists 34 at risk and 27 affected. It also lists 26 deaths. These are counts in the registry’s safety categories; they are not, on their own, a comparison between treatments or proof that ipatasertib caused an event.

The listed serious adverse event terms include diarrhea at 8.8%, rash maculo-papular at 5.9%, vomiting at 5.9%, anemia at 2.9%, cardiac arrest at 2.9%, and fatigue at 2.9%. These values are reproduced as reported. The registry record does not provide additional context in these figures about event timing, severity beyond the serious-event category, recurrence, or attribution. The term list should therefore not be read as a complete account of every safety outcome.

The number of deaths is not identified as treatment-related, and the record does not establish a cause for each death. Counts of participants affected also do not describe duration or clinical course. Safety interpretation requires the categories to be kept distinct and the limits of the posted information to be recognized.

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

The record establishes that MATCH subprotocol Z1K is a phase II, single-group study of ipatasertib in patients with tumors with AKT mutations. It specifies a primary endpoint, objective response rate, and defines the eligible, treated, mutation-confirmed population for that endpoint. It also describes the response criteria and tumor-assessment schedule. These details explain what the primary outcome was intended to measure.

However, the registry record does not report the primary endpoint’s response count, percentage, or 90% confidence interval. It therefore does not show how many participants had an objective response or how precisely a response percentage was estimated. Planned enrollment of 35 cannot be substituted for the unreported analysis denominator, and no conclusion about the primary response outcome can be drawn from its definition alone.

The study has no control group. Even if a response proportion were available, a single-group result would describe outcomes among the analyzed participants and would not provide a randomized comparison with another treatment. It would not by itself isolate the effect of ipatasertib from other influences on observed outcomes. This design limitation is separate from whether the response endpoint was measured according to the stated criteria.

The posted safety counts provide additional descriptive information, but do not establish causation. The record lists serious and other adverse-event counts and deaths, along with several serious-event terms and percentages. It does not provide sufficient context in these figures to attribute events to treatment or to characterize their full clinical course.

In general, a registry entry can report a study’s design and planned outcome definitions without posting the results needed to answer the clinical question. In this case, the protocol description is informative about who was studied, what intervention was given, and how response was defined. The primary result, its uncertainty, and numerical results for the named secondary outcomes are not reported in the registry record. The absence of posted results should not be interpreted as evidence for or against a treatment effect.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way it links a molecularly selected population to a prespecified tumor-response outcome. The record focuses on cancers with AKT mutations and describes a common primary endpoint while recognizing that response classification differs by tumor type. For statisticians and clinical researchers, that makes the analysis population and the operational response criteria central to understanding what the endpoint represents.

Its single-group design also illustrates a basic distinction between describing an outcome and estimating a comparative treatment effect. A response percentage can summarize the experience of the analyzed group. Without a comparator, however, it cannot quantify a randomized contrast. The distinction remains important even when the outcome definition is clear and assessments occur on a planned schedule.

The record also highlights why reporting the denominator and uncertainty matters. An endpoint definition and planned enrollment do not reveal how many participants contributed to the final analysis. For a percentage, the analyzed population and the confidence interval are essential to judging how stable or precise an estimate may be. Here, the registry specifies an exact binomial interval method but does not post its limits or the response estimate.

Finally, named secondary outcomes and safety counts do not replace missing primary results. They provide context about the scope of planned outcomes and the categories recorded, but no numerical secondary outcome results are reported. This trial therefore offers a useful statistical reading exercise: separate design information, endpoint methods, descriptive safety counts, and outcome results, and avoid treating one category as a substitute for another.

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 direct limitation of interpretation is that the primary objective response result is not reported in the registry record. No response count, percentage, or confidence interval is posted, and the number included in the primary analysis is also not reported. This prevents assessment of both the endpoint’s observed value and its precision.

The trial is single-group, with no comparator and no masking. It can describe outcomes in the treatment group but cannot provide a randomized comparison. The registry record lists planned enrollment of 35, but does not state how many participants were ultimately treated, had mutation status confirmed, or were evaluable for tumor response.

Response classification is based on different named criteria for solid tumors, lymphoma, and glioblastoma. The registry record points to the master protocol for details, but those operational details are not reported in the registry record. The record also does not explain how missing or unevaluable assessments were handled, whether response confirmation was required, or how the analysis population was finalized.

Although progression-free survival and 6-month progression-free survival are named as secondary outcomes, their results and detailed analysis methods are not reported. The statistical analysis plan, multiplicity approach, sample-size justification, and interim-analysis details are also not reported in the registry record. These absences limit evaluation of the analysis choices and the context in which any findings would be interpreted.

The safety figures are counts and listed percentages without enough information to establish event attribution or clinical course. The registry status and study dates do not resolve these limitations or supply missing outcome data. Conclusions should remain confined to the design, endpoint definitions, and safety categories that are actually posted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing Ipatasertib as Potentially Targeted Treatment in Cancers With AKT Genetic Changes (MATCH - Subprotocol Z1K) — NCT06400251.
• Registry record last updated 2026-06-01; status last verified 2026-05.
• Results first posted 2025-08-26.
• 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

NCT06400251 is the phase II MATCH Treatment Subprotocol Z1K, testing ipatasertib in patients with tumors with AKT mutations. The study is recorded as single-group, with no masking and no comparator. Planned enrollment is 35; status is active, not recruiting. The National Cancer Institute is listed as sponsor.

Participants received ipatasertib 400 mg by mouth once daily on days 1–28 of 28-day cycles. The primary endpoint is objective response rate among eligible, treated participants with mutation status confirmed, assessed using tumor-type-specific criteria. A two-sided 90% exact binomial confidence interval is specified. The registry record does not report the primary response estimate or interval.

Progression-free survival and 6-month progression-free survival are listed as secondary outcomes. Safety counts include 13 affected by serious adverse events and 27 affected by other adverse events among 34 at risk in each category, and 26 deaths. These figures do not establish event attribution. The analysis plan, missing-data handling, and numerical secondary outcome results are not reported in the registry record.