Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W) (NCT04439240), a na phase 2 study. The primary outcome is Overall Response Rate (ORR).

2. Clinical Question

3. Trial Design

This was a phase II, single-group treatment study sponsored by the National Cancer Institute. The registry lists enrollment of 52 and a completed status. The recorded start date is 2016-05-31, and the primary completion date is 2019-06-06. These dates describe the registry record; they do not provide additional detail about recruitment or follow-up for individual participants.

The intervention was AZD4547, described as an FGFR inhibitor. The treatment group received the drug orally twice daily on days 1-28. Cycles were to repeat every 28 days in the absence of disease progression or unacceptable toxicity. The registry does not report the dose in the information available for this analysis.

Masking is listed as none, and allocation is listed as not applicable. This was therefore not a randomized comparison, and no like-for-like control group is identified. A single-group design can describe outcomes among people receiving the study treatment, but cannot separate treatment effects from other explanations using a concurrent randomized contrast.

The primary outcome was overall response rate. The registry also lists 6-month progression-free survival rate and progression-free survival as secondary outcomes. It reports three outcome measures in total, but does not report numerical results for the primary or secondary outcomes. The registry's eligibility criteria, any detailed statistical analysis plan, and a sample-size justification are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: To be assigned to a specific MATCH subprotocol, patients needed to submit a tumor biopsy for molecular characterization and those with molecular variants addressed by treatments included in the trial entered corresponding MATCH subprotocol. For subprotocol W, patients had to have tumors harboring aberrations in FGFR 1-3.

Overall Study

Reasons for not completing this period:

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

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: Eligible and treated patients

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR), measured over Assessed 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.

Overall response rate is the proportion of eligible and treated patients whose best overall response was either complete response or partial response. The registry describes response assessment using RECIST version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. The assessment schedule began at baseline, continued every 2 cycles for the first 26 cycles, and then every 3 cycles until disease progression, up to 3 years post registration.

As a binary endpoint, each patient contributes either as having had a complete or partial response, or as not meeting that response definition. The endpoint is used to describe the frequency of tumor responses in the defined analysis population. General statistical context: response rate offers a direct summary of whether a prespecified response category was observed, while not by itself describing how long a response lasted or whether progression-free survival improved.

The registry specifies a two-sided binomial exact confidence interval at the 90% level for the response rate. A confidence interval expresses the precision of an estimate under the stated statistical model. However, the observed response rate and interval are not reported in the registry record, so neither the estimated frequency nor its precision can be assessed from the recorded results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary proportion. Each eligible and treated participant is classified according to whether the best overall response met the definition of complete response or partial response. The overall response rate is then the proportion of participants who meet either response category. General statistical context: a proportion is a concise summary for an outcome with two categories, but its interpretation depends on a clear outcome definition and a clearly identified analysis population.

What the confidence interval describes

The registry specifies a two-sided binomial exact confidence interval at the 90% level. General explanation: a confidence interval gives a range of values compatible with the observed data under the statistical model and procedure used. Its width reflects uncertainty in the estimate; a less precise estimate generally has a wider interval. An interval is not a guarantee that the true value lies within its particular limits, nor does it supply a comparison with an untreated or alternative-treatment group.

The exact binomial method is a way to construct an interval for a proportion while accounting for the discrete nature of binary outcome data. The registry explicitly identifies this method for overall response rate. It does not report the estimate, the interval limits, or further details about the analysis beyond the endpoint definition and method. The interval therefore cannot be evaluated from this record.

How response was assessed

The registry states that best overall response was evaluated using RECIST version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. These named criteria provide disease-appropriate rules for classifying response. General explanation: standardized criteria can make outcome definitions more reproducible, but applying different criteria across disease groups does not make their underlying clinical assessments identical. The registry does not report the distribution of participants across these disease groups or subgroup response estimates.

The planned assessment schedule began at baseline, then occurred every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration. This describes the scheduled timing, not the amount of follow-up actually achieved by participants. Actual assessment completion, missed assessments, and the handling of participants without an evaluable response are not reported in the registry record.

What the single-group design allows

The study is recorded as single-group, with allocation not applicable and masking none. General explanation: a single-group study can estimate the frequency of an outcome among participants receiving the intervention, subject to how participants are selected, assessed, and included in analysis. It does not create a randomized concurrent comparison. Without such a comparison, the response proportion cannot on its own distinguish an intervention-associated outcome from other factors that might influence outcomes in the study population.

Non-masking means treatment allocation was not concealed through masking as listed in the registry. The record does not explain whether or how awareness of treatment could have affected response assessment, nor does it report independent review procedures. No additional procedures should be assumed.

What is not described

The registry identifies the primary outcome method but does not report a full statistical analysis plan, a sample-size justification, interim analyses, or numerical analyses. The record lists 52 participants as enrollment, but does not state the size of the eligible and treated population used for the primary endpoint. General explanation: an analysis population and its denominator matter because they determine which participants contribute to the estimated proportion. The distinction cannot be resolved from enrollment alone.

The record also lists 6-month progression-free survival rate and progression-free survival as secondary outcomes. Their analysis methods, estimates, and confidence intervals are not reported in the registry record. Methods for handling missing outcome data are not reported either. In the absence of those details and results, statistical interpretation should stay with the stated design and definitions rather than presume particular procedures or findings.

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 (AZD4547)")
n      <- c(48)
events <- c(4)
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 (AZD4547)  48  4  8.3  2.3  20.0  3.3  19.6  3.4  19.6

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies overall response rate as the primary outcome and lists 6-month progression-free survival rate and progression-free survival as secondary outcomes. It reports three outcome measures in total. No numerical estimates or analyses for these outcomes are reported in the registry record.

Multiplicity concerns arise when a study evaluates multiple outcomes or makes multiple statistical comparisons, because considering many results can affect the interpretation of chance findings. General explanation: a statistical plan may specify which outcome is primary and how other tests or intervals will be interpreted. The registry record identifies outcome roles, but does not report whether any multiplicity adjustment or hierarchy among secondary analyses was planned. No adjustment should therefore be assumed.

The primary endpoint population is described as eligible and treated patients. The registry lists enrollment of 52, but does not report the number of eligible and treated participants in the endpoint analysis or how exclusions, if any, were handled. The missing-data approach is not reported in the registry record. In particular, the record does not state how participants without an evaluable response, incomplete follow-up, or missing assessments were handled.

The listed assessment schedule and follow-up limit do not establish that every participant completed each assessment or was followed for the same duration. Actual follow-up and the amount of missing outcome information are not reported. As a result, it is not possible to assess whether missing data affected the response estimate or secondary outcomes.

The analysis population for safety is not fully described beyond the at-risk counts listed with the adverse-event information. The relation between those counts, the enrollment count, and the primary endpoint population is not reported. The registry also does not provide an analysis plan explaining how safety outcomes were summarized. These omissions limit the ability to reconstruct participant flow or compare outcome populations.

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: mucositis oral (14.3%), aspartate aminotransferase increased (8.2%), palmar-plantar erythrodysesthesia syndrome (6.1%), alanine aminotransferase increased (6.1%), anemia (4.1%).

The registry lists 49 participants at risk for serious adverse events and reports that 19 were affected in the AZD4547 treatment group. For other adverse events, it also lists 49 at risk and 41 affected. These are distinct categories in the safety information and should not be treated as interchangeable counts. General statistical context: seriousness is a regulatory classification, while severity describes how intense an event is; the two concepts are not equivalent.

The listed serious adverse-event terms and registry percentages are mucositis oral, 14.3%; aspartate aminotransferase increased, 8.2%; palmar-plantar erythrodysesthesia syndrome, 6.1%; alanine aminotransferase increased, 6.1%; anemia, 4.1%; and febrile neutropenia, 2.0%. These are the terms and percentages recorded; the information does not establish their cause or relationship to treatment.

The registry also lists 44 deaths for the treatment group. It does not report causes, timing, or attribution for these deaths in the information, so they cannot be interpreted as treatment-related from this count alone. The record does not provide additional detail about event duration, recurrence, or individual clinical courses.

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

The record describes a phase II study designed to assess overall response rate among eligible and treated patients with tumors bearing FGFR pathway aberrations. It names AZD4547 as the intervention and specifies the response definitions and assessment schedule. Those details explain what the study set out to measure, but they are not themselves evidence of an observed response.

The numerical primary outcome is not reported in the registry record. There is no reported overall response rate or confidence interval, and no numerical results are listed for the secondary progression-free survival outcomes. The record therefore cannot establish the frequency of response in the analyzed population, the precision of that estimate, or the observed survival outcomes.

Even if a response proportion were available, general statistical context is that a single-group estimate describes outcomes among people in that study. Without a concurrent randomized comparator, it cannot provide the same evidence as a direct randomized comparison of treatment strategies. The registry lists no control group, and the interpretation should reflect that design.

The study included a range of advanced or refractory cancers and used different response criteria for different disease contexts. The overall endpoint definition is therefore tied to the criteria named for each group. The registry does not report disease-specific results, so the record cannot support conclusions about response in any particular cancer subgroup.

The completed status indicates that the study is recorded as completed; it does not establish that results were posted. The most defensible interpretation is limited to the study design, treatment description, endpoint definitions, and safety counts that are recorded. No conclusion about whether AZD4547 did or did not produce a particular clinical outcome can be drawn from absent outcome estimates.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of a single-group phase II design using a binary response endpoint across several cancer contexts. Its primary outcome is defined as the proportion of eligible and treated participants with a best overall response of complete or partial response. The registry also identifies the response criteria and confidence-interval method, which are important parts of making an endpoint interpretable.

The record illustrates why outcome definitions and analysis populations matter. Enrollment is listed as 52, while the primary endpoint population is eligible and treated patients. Since the number in that analysis population is not reported, enrollment cannot automatically be substituted for the primary endpoint denominator. Clear reporting of participant flow and analysis populations is necessary to understand how an outcome estimate was formed.

The design also highlights the distinction between describing an outcome and comparing treatments. A single-group study can summarize outcomes among treated participants, but it has no randomized concurrent control group in this record. General statistical context: the absence of randomization means a treatment comparison cannot be isolated from other possible influences using the study design alone.

Finally, the registry record separates a detailed endpoint definition from the numerical outcome itself: it states how response was assessed, yet does not report the response estimate or interval. That gap matters because the statistical method explains how a result would be summarized, but cannot replace the result. For interpretation, complete reporting of estimates, uncertainty, analysis populations, and missing-data handling is central.

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 outcome interpretation is that the registry record does not report the overall response rate or its 90% confidence interval. It also does not report numerical results for the listed progression-free survival outcomes. Although the status is completed, the recorded status does not provide those missing estimates.

The single-group design has no randomized concurrent comparator. Results, if available, would describe outcomes in the treated study population rather than establish a randomized contrast. The record lists masking as none, and does not describe any independent response review or other procedures that might affect assessment.

The study covers several categories of advanced or refractory cancer, and response was assessed with different criteria for different disease contexts. The registry does not report subgroup sizes or outcome estimates, limiting interpretation across specific diagnoses. The eligibility criteria beyond the stated disease and FGFR alteration context are not reported in the registry record.

The endpoint population is eligible and treated patients, but its denominator is not reported. Enrollment is listed as 52; the record does not explain the relation between enrollment and the primary analysis population. Handling of missing assessments, incomplete response evaluations, and incomplete follow-up is also not reported. Although the planned assessment period extended up to 3 years post registration, actual follow-up is not stated.

The registry does not report the detailed statistical analysis plan, a sample-size justification, or interim analyses. It lists 49 participants at risk for safety summaries and 44 deaths, but provides no further information about death causes, timing, or attribution in the record available for interpretation. These limitations prevent fuller assessment of outcome precision, participant flow, and safety context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Testing AZD4547 as a Potential Targeted Treatment in Cancers With FGFR Genetic Changes (MATCH-Subprotocol W) — NCT04439240.
• Registry record last updated 2021-06-29; status last verified 2021-06.
• Results first posted 2021-06-29.
• 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

NCT04439240 is a completed phase II, single-group study sponsored by the National Cancer Institute. It studied AZD4547 in patients with tumors with FGFR pathway aberrations. Enrollment is listed as 52; the recorded start date is 2016-05-31 and primary completion date is 2019-06-06.

The primary outcome was overall response rate among eligible and treated patients, defined by complete or partial response and assessed with disease-specific criteria. The registry specifies a two-sided binomial exact 90% confidence interval. Secondary outcomes were 6-month progression-free survival rate and progression-free survival.

The registry record does not report numerical results for the primary or secondary outcomes. Safety information lists 19 of 49 participants affected by serious adverse events, 41 of 49 affected by other adverse events, and 44 deaths; causes and attribution are not reported in the information available.