Testing AZD1775 as a Potential Targeted Treatment in Cancers With BRCA Genetic Changes (MATCH-Subprotocol Z1I): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing AZD1775 as a Potential Targeted Treatment in Cancers With BRCA Genetic Changes (MATCH-Subprotocol Z1I) (NCT04439227), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

3. Trial Design

This is a phase II study within the MATCH treatment program, listed as Subprotocol Z1I. Its focus is adavosertib in patients with tumors containing BRCA1 or BRCA2 mutations. The registry records a single-group model, no masking, and allocation as not applicable. There is no listed control arm or randomized treatment assignment. The study therefore describes outcomes among participants treated with adavosertib rather than a direct comparison with another treatment.

The registry lists enrollment as 33. The listed intervention is adavosertib, also called AZD1775 in the study title. Participants receive it orally once daily on days 1–5 and 8–12 of each cycle. Cycles repeat every 21 days if disease progression or unacceptable toxicity has not occurred. The registry does not report the number of cycles received by participants or treatment exposure for individual participants.

The listed conditions include advanced and refractory malignant solid neoplasms and lymphomas, hematopoietic and lymphoid cell neoplasms, and refractory multiple myeloma. This range matters when interpreting a single overall response measure: the registry describes response criteria that accommodate different tumor types, rather than one uniform disease-specific criterion.

The registry records a start date of 2017-03-24, a primary completion date of 2020-05-29, and a status of active, not recruiting. These record fields describe the study’s administrative status and timeline; they do not substitute for outcome results. The primary outcome is objective response rate, and the listed secondary outcomes are 6-month progression-free survival and progression-free survival. The outcome estimates and analysis details are not reported in the registry record.

The registry’s background describes AZD1775 as a potential treatment intended to target WEE1. That rationale is a study premise, not evidence of an observed effect. The single-group design can describe outcomes in treated participants, but without a concurrent comparator it cannot isolate treatment effects from other explanations for those outcomes.

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 were assigned to this NCI-MATCH subprotocol (EAY131-Z1I) using a prospectively defined NCI-designed informatics rules algorithm (MATCHBOX). Adult patients with solid tumors carrying BRCA1/2 PVs were eligible if they had progressed on standard treatment or had no standard treatment available.

Overall Study

Reasons for not completing this period:

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

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 and started protocol therapy 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 3 cycles for the first 33 cycles and every 4 cycles thereafter until disease progression, up to 3 years post registration.

Objective response rate (ORR) is the percentage of analyzable patients whose tumors meet the criteria for complete or partial response. It is a binary-outcome summary: each patient is classified according to whether a response is recorded under the applicable response rules, and the rate summarizes the proportion classified as responders. The registry defines the primary-outcome population as eligible and treated, while its ORR definition refers to analyzable patients. The number included in the endpoint analysis is not reported in the registry record.

The registry specifies 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. It points to the master protocol for details on defining complete and partial response. Those criteria provide standardized rules for classifying tumor changes, with the applicable framework depending on tumor type.

ORR is used to describe the frequency of tumor shrinkage meeting response criteria. It does not, by itself, describe how long a response lasts, whether disease remains controlled, or how outcomes compare with an alternative treatment. The registry lists progression-free survival and 6-month progression-free survival as secondary outcomes, but does not report their estimates. It also specifies a two-sided binomial exact 90% confidence interval for ORR. Neither the observed ORR nor its interval is reported in the registry record, so the endpoint’s numerical result and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary response outcome summarized as a percentage: patients are classified as having a complete or partial response, or not meeting those response criteria. The registry defines ORR among analyzable patients and identifies the primary-outcome population as eligible and treated. Those descriptions do not give the number analyzed. The registry record does not report the response count, analyzed denominator, or ORR estimate, so no numerical interpretation of the endpoint is possible.

What does the confidence interval describe?

The registry specifies a two-sided binomial exact 90% confidence interval for ORR. General statistical explanation: a confidence interval is a range calculated from observed data to convey uncertainty about an underlying response proportion, under the chosen statistical model. The exact binomial method is designed for a binary outcome and does not rely on the same large-sample approximation as a normal-based interval. The interval’s width depends on the observed data and the analysis denominator. Because the registry does not report the estimate or interval, the precision of the study’s ORR cannot be assessed.

A 90% confidence interval is not a guarantee that the true response rate lies within a particular interval, and it is not a measure of the chance that an individual patient will respond. It quantifies statistical uncertainty in a group-level estimate according to a repeated-sampling interpretation. It also does not account for every possible source of uncertainty, such as outcome measurement differences or missing assessments.

Why do response criteria matter?

The registry names different response frameworks for different tumor types: 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. These criteria set rules for classifying complete and partial response. Standardized criteria support consistent assessment, but applying different frameworks across disease types means that an overall response summary combines classifications made under tumor-appropriate rules. The registry refers readers to the master protocol for further details; those details are not reported in this record.

The registry states that 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. This schedule describes planned assessment timing. It does not report how many assessments participants completed, the timing of individual responses, or how incomplete assessments were handled.

What does the single-group design imply?

General statistical explanation: a single-group study estimates outcomes in the participants who receive the intervention, but it has no concurrent randomized comparison to show what would have happened to similar participants under another treatment or care strategy. An observed response rate in such a study is descriptive. It cannot on its own separate the intervention’s contribution from differences in disease characteristics, participant selection, other care, or the natural course of disease.

The study is recorded as unmasked and single group, with allocation not applicable. The registry does not report whether outcome assessment was independently reviewed or whether any other safeguards were used to limit assessment bias. No assumption should be made about those procedures. The absence of masking can be relevant to study conduct, but the record does not establish that it changed any outcome classification.

How should planning illustrations be understood?

The registry includes planning assumptions for an illustration based on an observed effect: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect, and that time-to-event illustrations give total events while other illustrations give participants per arm. These assumptions describe a hypothetical planning exercise, not the actual single-group trial design. No numerical planning results are reported in the registry record.

General statistical explanation: sample-size planning asks how much information a future study might need to detect a specified effect under selected assumptions. It is not a measure of the probability that a completed study’s result is true. In particular, a sample-size calculation based on an observed effect does not constitute observed power and does not replace a prespecified design justification. The registry does not report the trial’s own sample-size justification, analysis plan, significance threshold for the primary endpoint, or any interim analysis plan.

Over-dispersion is a general concern when observed variation is greater than a simple statistical model assumes. For a binary endpoint, meaningful differences in risk across patient subgroups can make a single common response probability an imperfect summary. The registry lists several disease categories and multiple response frameworks, but it does not report a model allowing for over-dispersion, subgroup results, or an adjustment for heterogeneity. No such analysis should be inferred from the endpoint description.

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 (Adavosertib)")
n      <- c(30)
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 (Adavosertib)  30  1  3.3  0.1  17.2  0.6  16.7  0.8  16.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures: ORR as the primary outcome, along with 6-month progression-free survival and progression-free survival as secondary outcomes. It reports no analyses. Numerical results for these outcomes, including response counts and survival estimates, are not reported in the registry record.

When a study assesses multiple outcomes or conducts multiple statistical tests, the chance of obtaining at least one apparently notable result can change. General statistical explanation: multiplicity procedures may be used to control that chance, or a study may distinguish confirmatory outcomes from exploratory ones. The registry record does not report whether multiplicity was considered, whether any adjustment was planned, or how the secondary outcomes were intended to be interpreted. The number and nature of any additional analyses are also not reported.

The ORR definition refers to analyzable patients, and the primary-outcome population is listed as eligible and treated. The record does not explain the operational rules used to determine analyzability, how missing tumor assessments were handled, or whether participants without an evaluable assessment were excluded or classified in another way. The number of participants with missing response data and reasons for missingness are not reported. Without those details, the relationship between the enrolled group and the endpoint analysis population cannot be assessed.

The registry gives an assessment schedule and identifies progression and unacceptable toxicity as conditions affecting continued treatment, but does not report how incomplete follow-up, withdrawals, or censoring were handled for progression-free survival. It also does not report analysis-population definitions beyond the endpoint descriptions. No missing-data method, sensitivity analysis, or prespecified statistical analysis plan is 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: neutrophil count decreased (21.2%), fatigue (12.1%), nausea (12.1%), platelet count decreased (12.1%), white blood cell decreased (12.1%).

The registry lists 33 participants at risk for serious adverse events and 18 participants affected in the treatment group. It lists 33 at risk for other adverse events and 26 affected. These are separate group summaries; the record does not state whether the participants affected in one category overlap with those affected in the other. The figures describe counts, not the number of distinct event episodes.

The listed serious adverse-event terms include neutrophil count decreased at 21.2%, and fatigue, nausea, platelet count decreased, white blood cell decreased, and hyperglycemia each at 12.1%. The registry record does not provide additional detail about event duration, severity grades, timing, resolution, or the denominator used for each listed term. The percentages therefore should be read as registry-reported event figures, not as a full account of each participant’s safety experience.

The record lists 27 deaths in the treatment group. It does not report cause, timing, or attribution for these deaths, so they cannot be interpreted as deaths caused by treatment. Serious adverse events and deaths are safety observations; without further detail, they do not establish causation. The registry’s figures also do not provide a comparison with an untreated or alternative-treatment group.

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

The registry record establishes that a phase II, single-group study evaluated adavosertib in patients with tumors containing BRCA1 or BRCA2 mutations. It specifies the treatment schedule, an ORR primary endpoint, response criteria for different tumor types, and progression-free survival outcomes. These details describe the study question and measurement approach.

The record does not report the ORR result, response counts, or confidence interval. It also does not report results for the secondary progression-free survival outcomes. Therefore, no conclusion about the frequency of observed responses, the precision of an estimate, or the observed time-to-event outcomes can be drawn from the registry record. Missing results should not be interpreted as evidence that no responses occurred or that any outcome had a particular value.

Even if a response estimate were available, a single-group result would describe the treated study population rather than provide a randomized comparison. Such a result alone would not show what would have happened to comparable participants without adavosertib or under a different treatment. Differences in tumor type, participant selection, other care, and the course of disease can affect observed outcomes. The record does not include a control group that could address these alternative explanations through direct comparison.

The study’s broad set of listed disease conditions and tumor-specific response criteria also calls for care when interpreting an overall summary. The registry does not report disease-specific response estimates or subgroup analyses. Likewise, the listed safety counts and terms describe reported events but do not establish that the intervention caused them. They cannot be compared with another group in this single-group record.

Accordingly, the appropriate reading is limited: the record describes a trial designed to assess tumor response and other outcomes in a selected population, but it does not provide the outcome estimates needed to judge what the study observed. It does not establish a treatment effect, comparative benefit, or treatment-related harm.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a defined response-measurement framework and the absence of posted outcome estimates. The registry specifies ORR, identifies the response criteria, and names a two-sided binomial exact 90% confidence interval. Those details make clear what kind of estimate the study intended to report. Without the estimate, response count, denominator, or interval, however, the result’s magnitude and precision remain unknown.

The single-group design is central to interpreting the study. It can describe outcomes among participants who received adavosertib, but it does not create a direct comparison with another treatment. Any outcome estimate from such a design would need to be distinguished from a causal treatment effect. This distinction is especially important where the registry lists a range of tumor and lymphoma conditions and different response frameworks.

The record also makes visible a population-definition issue: the primary outcome population is described as eligible and treated, while the ORR definition refers to analyzable patients. Reporting the analyzed denominator and explaining how participants with missing assessments were handled would help readers understand how the result relates to enrollment. Those details are not reported in the registry record.

Finally, the presence of secondary outcomes and safety summaries does not replace a complete statistical report. Outcome estimates, uncertainty intervals, missing-data methods, multiplicity handling, and analysis details are needed to interpret the results fully. Their absence limits what can be learned from the registry record, without implying that the study did or did not observe a particular outcome.

15. Limitations

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

The main limitation for statistical interpretation is that the registry record does not report the primary ORR estimate, response count, analysis denominator, or confidence interval. The secondary outcomes are named but their results are not reported. As a result, the record does not permit assessment of observed response frequency, precision, progression-free survival, or 6-month progression-free survival.

The single-group design provides no concurrent comparator, and the study is unmasked. The design can describe outcomes among treated participants, but cannot independently separate treatment effects from other explanations for those outcomes. The record does not report procedures for independent response review or other methods that might address assessment concerns.

The listed population spans advanced and refractory solid tumors, lymphomas, hematopoietic and lymphoid cell neoplasms, and refractory multiple myeloma. The registry also names different tumor-response criteria for different disease types. It does not report subgroup estimates or explain how an overall response summary would account for differences among these groups. An aggregate outcome, if reported, could therefore be difficult to apply to any one listed disease category without additional results.

The relationship between enrollment and endpoint analysis is unclear because the registry describes the ORR population as analyzable patients but does not report how many were analyzed. Missing assessments, withdrawals, protocol deviations, censoring rules, and sensitivity analyses are not reported. The registry also does not report a sample-size justification, formal statistical analysis plan, multiplicity approach, or interim analysis plan. These omissions restrict evaluation of the planned and conducted analyses; they do not establish that particular methods were or were not used outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing AZD1775 as a Potential Targeted Treatment in Cancers With BRCA Genetic Changes (MATCH-Subprotocol Z1I) — NCT04439227.
• Registry record last updated 2026-11-03; status last verified 2026-10.
• Results first posted 2026-10-06.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT04439227 is a phase II, single-group, unmasked study of adavosertib (AZD1775) in patients with tumors containing BRCA1 or BRCA2 mutations. The registry lists enrollment as 33 and a regimen of oral treatment once daily on days 1–5 and 8–12 of repeating 21-day cycles, in the absence of disease progression or unacceptable toxicity. The primary endpoint is ORR, defined using tumor-specific response criteria, with a planned two-sided binomial exact 90% confidence interval. Progression-free survival and 6-month progression-free survival are listed as secondary outcomes. The record lists serious and other adverse-event counts and terms, as well as 27 deaths, without further attribution detail. It does not report outcome analyses or numerical efficacy results, and it does not report the statistical analysis plan, missing-data methods, or multiplicity approach.