Futibatinib and Pembrolizumab for Treatment of Advanced or Metastatic FGF19 Positive BCLC Stage A, B, or C Liver Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Futibatinib and Pembrolizumab for Treatment of Advanced or Metastatic FGF19 Positive BCLC Stage A, B, or C Liver Cancer (NCT04828486), a na phase 2 study. The primary outcome is Progression-free Survival (PFS).

2. Clinical Question

3. Trial Design

This is a phase II, single-group study sponsored by Mayo Clinic. The registry lists an enrollment of 14 and identifies the study as completed. The start date is 2021-08-17, and the primary completion date is 2024-09-18. Allocation is recorded as NA, and masking is listed as none. These design features mean the study evaluates outcomes among participants receiving the combination but does not provide a randomized, concurrent treatment comparison.

The treatment group received futibatinib and pembrolizumab. The registry description specifies oral futibatinib on days 1-21 for cycles 1-9 and days 1-42 for later cycles, with pembrolizumab given intravenously on day 1. It describes cycles as repeating every 21 days for cycles 1-9 and every 42 days thereafter, for up to 2 years in the absence of disease progression or unacceptable circumstances. The treatment description in the registry record is truncated at its final phrase, so further details are not reported there.

The study focused on patients with FGF19-positive hepatocellular carcinoma at BCLC stage A, B, or C, described as advanced or metastatic and treated after first-line therapy. Other eligibility requirements, the definition or measurement procedure for FGF19 expression, and baseline participant characteristics are not reported in the registry record. The record lists overall response rate, overall survival, incidence of adverse events, and change in quality of life among the secondary outcomes. It does not provide outcome estimates for those endpoints in the registry record for this analysis.

A single-group phase II design can describe outcomes observed among participants who received the treatment regimen. Without a concurrent control group, outcomes cannot establish how the same participants would have fared under another treatment. The design and limited enrollment also mean that estimates, if reported, would need to be read with attention to their uncertainty and the trial’s specific population.

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.

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS), measured over 6 months.

The primary endpoint is the percentage of participants alive and progression free at 6 months. The record defines 6 months as 27 weeks and describes progression-free survival as the length of time from study registration until disease progression. Progression was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The endpoint is estimated using the Kaplan-Meier method and is to be reported with a 95% confidence interval.

In general, a time-to-event endpoint accounts for both how long participants are observed and whether the event of interest is recorded during that observation. The Kaplan-Meier method estimates the probability of remaining free of the specified event over time, including when participants have differing follow-up. For this study, the reported quantity of interest is the estimated percentage alive and progression free at the specified time point. It is not a comparison of treatment groups, because the trial has only one group.

This endpoint offers a time-specific summary of disease progression experience, while retaining information about when progression occurs. Its interpretation depends on the endpoint definition, how progression is assessed, follow-up, and the handling of participants whose outcome status is not fully observed. Those operational details are not reported in the registry record. The registry record also does not report the estimated percentage at 27 weeks or its confidence interval, so the magnitude and precision of the primary result cannot be assessed from the available results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the Kaplan-Meier estimate represent? The primary outcome is a time-to-event measure summarized as the percentage alive and progression free at 6 months, which the registry defines as 27 weeks. The study defines progression-free survival as time from registration until disease progression and describes progression assessment using RECIST version 1.1. The Kaplan-Meier method estimates the proportion remaining free of the specified event over time. In general, it can use partial follow-up from participants who have not experienced the event by their last observation, rather than requiring every participant to have the same follow-up duration.

The method relies on information about event times and follow-up status. In general, participants whose event status is not observed through the analysis time may be censored at their last known follow-up. The method’s interpretation depends on appropriate handling of censoring and adequate follow-up. The registry record does not report the censoring rules, follow-up distribution, event count for the primary endpoint, or the number of participants contributing information at 27 weeks. These details are therefore not available for assessing how much information supports the time-specific estimate.

How should the confidence interval be understood? The primary endpoint is described as a percentage with a 95% confidence interval. In general, a confidence interval communicates statistical uncertainty around an estimate under the assumptions of the estimation procedure. A narrower interval indicates greater precision than a wider interval, but precision is not the same as freedom from bias. It also does not make a single-group study into a controlled comparison. The record does not report the endpoint estimate or its interval, so neither the location nor width of the interval can be interpreted.

What does the study design permit? The study is single-group, with allocation marked NA and no masking. There is no randomized comparator in the record. In general, randomization helps make treatment groups comparable with respect to measured and unmeasured factors, while a concurrent control helps distinguish outcomes under different treatment strategies. Without those features, observed outcomes in this study describe participants receiving the combination; they do not directly quantify what would have happened to comparable participants under another strategy. The registry record does not report a prespecified statistical analysis plan or adjusted comparative analysis.

What can the safety counts say? The safety summary lists participants at risk and participants affected for serious and other adverse events. In general, a count of affected participants describes whether at least one event was recorded for each participant under the relevant summary definition; it need not convey the total number of event episodes. The registry record does not report the detailed definitions used for these safety categories, event duration, severity grading, attribution, or whether individual participants experienced more than one listed event term. The listed term percentages should be read as entries in the registry summary, not as a complete description of each participant’s experience.

The record also lists deaths, but does not provide the timing, causes, or attribution needed to interpret that entry as a treatment-related safety measure. In general, an all-cause death count, a treatment-emergent event count, and a count of deaths attributed to treatment are different quantities. They should not be assumed to be interchangeable. The registry record does not report which interpretation applies to the death entry beyond listing it in the safety summary.

How should planning illustrations be distinguished from trial findings? Any sample-size calculations in the surrounding material are planning illustrations based on the observed effect, with assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These calculations do not describe the actual design of this single-group trial, and they are not observed power. The registry record does not report that these assumptions formed part of the trial’s own planning or statistical design. In general, planning calculations explore what a hypothetical design might require under stated assumptions; they do not establish the reliability of the observed result.

For time-to-event calculations, the planning description refers to a total number of events, while other planning illustrations refer to participants per arm. Such hypothetical planning quantities should not be confused with observed enrollment, observed endpoint events, or the number of participants in this study. The registry record lists enrollment of 14 but does not report the primary endpoint event count or the numerical estimate required to evaluate the observed effect.

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 (Futibatinib, Pembrolizumab)")
n      <- c(13)
events <- c(3)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Treatment (Futibatinib, Pembrolizumab)  13  3  23.1  5.0  53.8  8.2  50.3  8.4  50.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes: overall response rate, overall survival, incidence of adverse events, and change in quality of life. It does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a strategy for interpreting multiple statistical tests. These details are not reported in the registry record. In general, when multiple outcomes are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of the tests. The outcome list alone does not show how this issue was handled.

Missing-data procedures are also not reported in the registry record. The primary endpoint is time-to-event, for which follow-up and censoring are relevant; the registry does not state how incomplete follow-up, withdrawal, or unavailable progression assessments were handled. It does not report a missing-data strategy for quality-of-life assessments. In general, the consequences of missing observations depend on why data are absent and on the assumptions used in the analysis. Those assumptions cannot be evaluated from the outcome descriptions alone.

The analysis population is not reported in the registry record. The record does not specify which participants were included in the primary analysis, whether any participants were excluded from particular outcome analyses, or how participants who did not complete treatment were handled. The enrollment figure should not be assumed to equal the number analyzed for every endpoint, especially because endpoint-specific analysis populations and available follow-up are not stated.

The record lists 5 outcome measures and no analyses. It does not provide outcome estimates, analysis populations, or detailed statistical methods for the secondary endpoints. Consequently, there is insufficient information to assess how missing observations, multiple outcomes, or analysis-set choices may affect the reported findings.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anemia (7.7%), myocarditis (7.7%), abdominal pain (7.7%), nausea (7.7%), vomiting (7.7%).

The registry safety summary lists 13 participants at risk for serious adverse events and 5 affected. It lists 13 at risk for other adverse events and 12 affected. These are separate summary categories, and the record does not explain whether a participant could be represented in both. The counts describe affected participants in the registry summary; they do not indicate the total number of event episodes or the duration of events.

The listed serious adverse-event terms are anemia, myocarditis, abdominal pain, nausea, vomiting, and edema limbs. Each term is accompanied by a reported percentage of 7.7%. These entries do not show the full event descriptions, timing, severity grades, outcomes, or attribution to study treatment. The registry record does not report whether the listed terms include all serious events or only selected terms.

Deaths are listed as 8. The record does not report when these deaths occurred, their causes, whether they were considered treatment related, or how they relate to the adverse-event categories. The death entry should therefore be read as a registry summary count, not as evidence of a specific causal relationship. Differences between the safety-summary counts should not be used to infer unreported participant-level overlap or event histories.

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

This study addresses a defined clinical research question: the experience of patients with FGF19-positive advanced or metastatic hepatocellular carcinoma after first-line therapy who received futibatinib with pembrolizumab. Its primary endpoint is the estimated percentage alive and progression free at 6 months, defined as 27 weeks. The record gives the endpoint definition and planned use of Kaplan-Meier estimation, but does not report the numerical estimate or its 95% confidence interval. The observed primary result and its precision therefore cannot be evaluated from the registry record.

The single-group design means the study can describe outcomes among participants who received the combination, but it does not provide a randomized comparison with another treatment. Any outcome observed in that group would not, by itself, establish that the combination caused the outcome or show how it compares with an alternative. The record also cannot isolate the contribution of futibatinib from that of pembrolizumab.

The safety summary gives affected-participant counts and selected serious adverse-event terms, as well as a death count. It does not give the clinical context needed to determine event timing, attribution, severity grading, or causal relationships. These registry entries therefore support only a limited description of the recorded safety information.

In general, statistical estimates summarize observed data under specific methods and assumptions. They do not remove uncertainty, and a confidence interval—when reported—does not overcome a design’s lack of a concurrent comparator. Here, the absence of primary endpoint results and analysis details limits interpretation further. The registry record does not report numerical results for the listed secondary outcomes, nor does it report the analysis population, missing-data approach, or multiplicity strategy. The study’s question and design are identifiable, but its treatment effect and comparative performance are not established by the information reported in the registry record.

14. Why This Trial Matters Statistically

The study is statistically notable because it focuses on a specified population: patients with FGF19-positive advanced or metastatic hepatocellular carcinoma at BCLC stage A, B, or C after first-line therapy. It evaluates a combination regimen in a phase II, single-group design and names a time-specific progression-free survival outcome. That makes the research question and its target population clear at a high level, even though further eligibility and participant-characteristic details are not reported in the registry record.

The primary endpoint uses time-to-event information rather than only a simple count at the end of treatment. In general, a time-to-event approach can make use of follow-up over time and estimate the proportion remaining event free at a defined point. The record specifies Kaplan-Meier estimation, a 95% confidence interval, and an assessment of progression using RECIST version 1.1. Those choices make the intended form of the primary outcome understandable.

The limits are equally important. A single-group study does not provide a randomized comparison, and enrollment is listed as 14. The primary numerical result and its confidence interval are not reported in the registry record, preventing assessment of the observed endpoint or its precision. The registry’s safety summary gives selected counts and terms but lacks detailed event context. The listed secondary outcomes also have no reported estimates in the available record.

For statistical interpretation, this case illustrates why a clearly defined endpoint and estimation method do not alone provide enough information to judge a treatment result. Numerical results, uncertainty, analysis populations, follow-up, and the design’s capacity for comparison all matter. The record identifies several of these design elements, while leaving the primary result and important analysis details unreported.

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 interpreting efficacy is that the registry record does not report the primary endpoint estimate or its 95% confidence interval. Without those values, the six-month progression-free survival result cannot be described quantitatively, and its precision cannot be assessed. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study is single-group and has no concurrent randomized comparator. Its findings, if available, would describe outcomes among participants receiving futibatinib with pembrolizumab rather than establish a comparative treatment effect. The record does not report details that would permit assessment of baseline prognostic characteristics, the representativeness of the enrolled group, or variation in clinical care.

The enrollment is listed as 14, while the safety summary lists 13 participants at risk for serious and other adverse events. The registry record does not explain this difference or provide endpoint-specific analysis populations. The number of participants contributing to the primary endpoint estimate, the amount of follow-up, and the number of progression events are not reported.

Other limitations include the absence of reported methods for missing data, censoring, multiplicity, and analysis-set selection. The safety information does not include event timing, severity grades, attribution, or detailed death context. The registry record also does not report participant characteristics or fuller eligibility criteria. These gaps limit both the statistical assessment of the results and the clinical context in which the recorded outcomes could be understood.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Futibatinib and Pembrolizumab for Treatment of Advanced or Metastatic FGF19 Positive BCLC Stage A, B, or C Liver Cancer — NCT04828486.
• Registry record last updated 2025-11-18; status last verified 2025-10.
• Results first posted 2025-10-29.
• 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

The registry record describes a completed phase II, single-group study sponsored by Mayo Clinic, with enrollment of 14. It began on 2021-08-17 and has a primary completion date of 2024-09-18. Participants had FGF19-positive advanced or metastatic hepatocellular carcinoma at BCLC stage A, B, or C after first-line therapy and received futibatinib with pembrolizumab.

The primary endpoint was the percentage alive and progression free at 6 months, defined as 27 weeks, estimated using Kaplan-Meier and assessed for progression with RECIST version 1.1. Its numerical estimate and 95% confidence interval are not reported in the registry record. Listed secondary outcomes include overall response rate, overall survival, adverse events, and change in quality of life; their estimates are not reported in the record.

The safety summary lists serious and other adverse-event counts, selected serious-event terms, and deaths, but does not provide detailed attribution or clinical context. The record does not report the analysis population, missing-data strategy, or multiplicity approach.