Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation (NCT04390243), a na phase 2 study. The primary outcome is Objective Response Rate (ORR) at 24 Weeks.

2. Clinical Question

The clinical question is about response observed during treatment, rather than whether the combination improves outcomes relative to another treatment. In a single-group trial, response can be described among participants who received the regimen, but there is no randomized concurrent group to establish a comparative treatment effect. The listed secondary outcomes include progression-free survival, overall survival, duration of response, time to response, and the number of patients with Grade 3+ adverse events. Those outcomes provide different views of disease course, response duration, and safety, but their results are not reported in the registry record.

3. Trial Design

This is a phase II, single-group trial sponsored by Academic and Community Cancer Research United. The registry lists an enrollment of 6 and a status of terminated. The recorded start date is 2020-11-16, and the primary completion date is 2023-11-01. The reason for termination is not reported in the registry record.

All participants were assigned to the treatment group described as encorafenib and binimetinib. The treatment description specifies oral encorafenib once daily and oral binimetinib twice daily on days 1-25. Cycles repeat every 28 days for up to 36 cycles, unless disease progression or unacceptable toxicity occurs. The registry record does not provide further information about treatment adherence, dose changes, or how many cycles participants received.

Allocation is recorded as NA, masking as none, and the model as single group. These details indicate that the design is not a blinded randomized comparison. Consequently, the record cannot support a direct randomized estimate of how outcomes differ between the combination and a control treatment. Although the brief summary refers to usual treatment, no concurrent usual-treatment group is described.

The primary endpoint is objective response rate at 24 weeks. The registry defines an objective response as a complete or partial response confirmed by a scan at least 4 weeks after the initial scan, with disease status assessed using RECIST version 1.1. Six outcome measures are listed, including the primary endpoint and secondary measures. The registry record contains no analysis entries and does not report outcome estimates. Details such as the planned analysis population, handling of participants without an evaluable scan, and reasons for termination 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.

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 Objective Response Rate (ORR) at 24 Weeks, measured over 24 weeks.

The primary endpoint, objective response rate at 24 weeks, is intended to describe the proportion of participants who have a complete or partial response by the specified assessment time. The registry requires a confirmation scan not less than 4 weeks after the initial scan and identifies RECIST version 1.1 as the assessment standard. This confirmation requirement helps distinguish a response sustained long enough to be confirmed from a finding on a single scan.

General: An objective response endpoint gives a categorical summary of tumor response under prespecified assessment criteria. It can be useful in a phase II study because it focuses on whether participants meet a defined response threshold. It does not, by itself, describe how long a response lasts, how long participants live, or how outcomes compare with another treatment. The registry lists duration of response, progression-free survival, and overall survival as separate secondary outcomes, reflecting that these questions are distinct from response occurrence.

The registry identifies the endpoint unit as a percentage of patients and states that a final point estimate and corresponding 95% confidence interval will be reported. However, the observed response estimate, its confidence interval, the denominator used for the calculation, and the number of participants with an evaluable assessment are not reported in the registry record. Therefore, the endpoint definition is available, but its observed value and precision cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical feature of this trial is its single-group design. The primary question concerns the observed objective response rate at 24 weeks among participants treated with binimetinib and encorafenib. The registry record does not report an observed response estimate or a corresponding confidence interval, so statistical interpretation must focus on what the planned measure means and what information is missing.

What does the response rate represent?

The registry defines an objective response as a complete or partial response with a confirmation scan not less than 4 weeks after the initial scan. Disease status is assessed using RECIST version 1.1. In general, a response rate is a proportion: participants meeting the response definition form the numerator, and a defined analysis population forms the denominator. The registry lists the unit as a percentage of patients, but does not report the numerator, denominator, or analysis population. The resulting rate cannot be reconstructed from the information in the registry record.

The assessment time is 24 weeks. This makes the endpoint a time-specific summary rather than a statement that participants responded at any point during all follow-up. The definition requires confirmation, which makes the timing of scans and the availability of follow-up relevant. The registry record does not say how assessments outside the planned time, missing scans, or early discontinuations were handled.

What does a confidence interval add?

The registry states that the final point estimate and its 95% confidence interval will be reported. General: a confidence interval expresses the uncertainty associated with an estimate under a statistical procedure. It helps readers judge how compatible the data are with a range of possible underlying response rates. It is not a guarantee that the true value lies within the interval, and it does not address limitations such as selection, missing assessments, or the absence of a comparator.

For a response percentage, the amount of information depends in part on how many participants contribute to the estimate and how many meet the response definition. The registry lists enrollment of 6, but enrollment alone does not establish the endpoint denominator. Without the response count and analysis population, neither the estimate nor its precision can be evaluated. The interval itself is not reported in the registry record.

Why does the single-group design matter?

In a randomized comparative trial, treatment groups can support a direct estimate of the difference between assigned strategies, subject to the study's assumptions and conduct. This trial is listed as a single group, with allocation NA and no masking. There is no concurrent control arm in the registry description. Accordingly, the primary endpoint is descriptive for the treated group rather than a randomized contrast. A response rate, if reported, would not isolate the effect of the combination from other influences on response.

The brief summary's reference to usual treatment does not establish a control group. The record does not describe a direct comparison with usual treatment, a historical control analysis, or a benchmark threshold. Any such protocol details or statistical comparisons are not reported in the registry record.

What can be learned from the secondary outcomes?

The registry lists progression-free survival, overall survival, duration of response, time to response, and the number of patients with Grade 3+ adverse events among the secondary outcomes. These measures address different aspects of the clinical course. General: time-to-event outcomes account for the time until a defined event, while duration of response is relevant only to participants who achieve a response. Their interpretation depends on event definitions, follow-up, censoring rules, and analysis populations. Those details and the corresponding results are not reported in the registry record.

The entry lists six outcome measures and zero analysis entries. This means the registry record does not contain posted analysis results to assess for these outcomes. It does not establish why analyses are absent or whether analyses were conducted outside the registry record. Statistical methods for the secondary outcomes, including any censoring rules or adjustment procedures, are not reported in the registry record.

How should planning calculations be understood?

General: a sample-size calculation is a planning exercise that describes the number of observations needed under stated assumptions. It is not an outcome and it is not observed power. A planning illustration based on an observed effect does not establish that the trial was originally designed with those assumptions, and it cannot substitute for the trial's observed estimate or confidence interval. The registry record does not report the trial's sample-size justification or its design assumptions.

The planning illustration uses equal allocation between two arms, while the registered trial is single group. That mismatch means the illustration's assumptions do not describe the enrolled trial design. Since the primary outcome result is not reported in the registry record, the observed effect on which an effect-based illustration would depend is unavailable in the record. No interpretation of such a planning calculation can establish the trial's power, adequacy, or efficacy findings.

What remains essential for statistical interpretation?

Readers would need the response count, the denominator and analysis population, the confidence interval, and the handling of missing or unevaluable assessments to interpret the primary endpoint. For the secondary outcomes, event counts, follow-up information, definitions, censoring methods, and estimates are also important. These items are not reported in the registry record. Without them, the statistical account is limited to the endpoint definitions, design description, enrollment, status, and posted safety counts.

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 (Encorafenib, Binimetinib)")
n      <- c(6)
events <- c(2)
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 (Encorafenib, Binimetinib)  6  2  33.3  4.3  77.7  9.7  70.0  9.9  71.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists an objective response endpoint as primary and identifies secondary outcomes including progression-free survival, overall survival, duration of response, time to response, and the number of patients with Grade 3+ adverse events. It also lists six outcome measures in total. The registry record does not report how many hypotheses were formally tested, whether any outcomes were designated exploratory, or whether the analyses used an adjustment for multiple comparisons. A multiplicity strategy is not reported in the registry record.

General: when multiple outcomes or multiple statistical tests are examined, the chance of obtaining a seemingly notable result by chance can increase. Prespecifying a primary endpoint and distinguishing it from secondary or exploratory analyses can help readers understand the intended hierarchy. Without a reported statistical analysis plan or results, the role of any such hierarchy cannot be assessed.

The registry record contains zero analysis entries. This indicates that analysis results are not posted in the record; it does not explain whether analyses were performed elsewhere. No primary endpoint estimate, confidence interval, or secondary outcome results are reported in the registry record.

The record does not describe the analysis population for the primary endpoint, how participants without a 24-week assessment were treated, or how missing data were handled. It also does not report whether participants who discontinued treatment or lacked a confirmation scan were included in an analysis. These details are important because missing outcome information can affect both the denominator and the interpretation of a response rate.

The registry lists enrollment of 6, but the number enrolled is not necessarily the number assessed or included in each outcome analysis. Analysis populations, missing-data methods, and sensitivity analyses are not reported in the registry record. As a result, the extent to which the posted safety counts and intended efficacy outcome refer to the same participants or follow-up period cannot be determined.

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: disease progression (16.7%), acute kidney injury (16.7%).

The registry reports safety figures for the treatment group, with six participants at risk for serious adverse events and one affected. It reports six participants at risk for other adverse events and six affected. The record also lists 4 deaths. These are descriptive counts; the registry does not provide enough detail to establish whether an event or death was caused by treatment.

The most frequently listed serious adverse event terms are disease progression and acute kidney injury, each reported as 16.7%. These percentages are presented as registry entries and should be read in the context of the small enrollment. The record does not state the timing, duration, severity details beyond the serious-event classification, or the number of events per affected participant for these terms.

General: serious adverse events and other adverse events are distinct reporting categories, and counts can describe participants rather than the total number of event episodes. The registry record does not define the counting rules for these figures or clarify whether the categories overlap. The six participants reported with other adverse events should therefore not be interpreted as six separate event types or as evidence of a particular severity level.

The 4 deaths are a count, not an attribution statement. Cause, timing, and relationship to treatment are not reported in the registry record. Safety counts from a small single-group trial cannot establish comparative risk without a suitable comparator and fuller context.

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

The registry record establishes that a phase II, single-group study evaluated binimetinib and encorafenib in patients with pancreatic malignancies and a somatic BRAF V600E mutation. It describes an objective response rate at 24 weeks as the primary endpoint, defines response using RECIST version 1.1, and specifies a confirmation scan. It also records enrollment of 6, a terminated status, and selected safety figures.

However, the registry record does not report the primary response rate, its confidence interval, or the analysis population. It therefore does not show how many participants met the response definition or how precisely any estimated response rate was measured. Missing results cannot be interpreted as a null result, a positive result, or an estimate of zero.

The design also does not establish a comparative treatment effect. Since the trial is listed as single group and has no concurrent comparator, outcomes among its participants cannot by themselves show how the combination compares with usual treatment or another regimen. The summary's mention of usual treatment does not change the registered design or establish that a comparison was conducted.

The registry's safety counts describe events recorded in the treatment group, but do not establish causality. The record does not report the cause or timing of deaths, or whether events were judged related to treatment. Likewise, the terminated status does not reveal why the study ended; the reason is not reported in the registry record.

General: a trial result is best understood by considering its estimate, uncertainty, design, analysis population, and completeness of follow-up together. Here, essential outcome estimates and analysis details are absent from the registry record. The entry can be used to understand the planned endpoint and basic study structure, but it cannot support a conclusion about the magnitude or precision of the observed response, comparative benefit, or causal safety effects.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported endpoint result are both necessary for statistical interpretation. The registry specifies objective response rate at 24 weeks, defines a confirmed response, and identifies RECIST version 1.1. Those details describe what the study intended to measure. But without the observed response count, denominator, and confidence interval, readers cannot assess the estimated response or its precision.

The single-group structure is also statistically important. It permits description of outcomes among the treated participants, but it does not provide a randomized comparison. That distinction remains important even when a study's summary refers to usual treatment. A comparator must be part of the design or a clearly described analysis before a comparative effect can be assessed.

The small enrollment makes transparent reporting particularly important. General: in a small study, outcomes for individual participants can have considerable influence on a summary proportion, and uncertainty may be substantial. Reporting the denominator and interval allows readers to see that uncertainty rather than relying on a percentage alone. Neither is reported for the primary endpoint in the registry record.

The entry also demonstrates the difference between planned outcome definitions and posted analyses. Several secondary outcomes are named, but the record contains no analysis entries. Without estimates and methods, readers cannot determine how those outcomes were analyzed or interpret their uncertainty. The same principle applies to missing-data methods and analysis populations: they shape the meaning of the result and should be described for an endpoint to be fully evaluated.

Finally, the status and safety counts are not self-explanatory. A terminated status does not provide its own explanation, and event counts do not establish treatment attribution. The reason for termination and important safety context are not reported in the registry record. These distinctions help prevent conclusions that go beyond what the record documents.

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 of the registry information is the absence of a posted efficacy result. Although the primary endpoint and assessment criteria are specified, the response rate, confidence interval, response count, and analysis denominator are not reported in the registry record. The planned endpoint can be described, but its observed magnitude and precision cannot be evaluated.

The study is registered as a single group, with allocation NA and no masking. There is no concurrent control group described, so the study cannot yield a randomized comparison against usual treatment. The brief summary's reference to usual treatment does not provide the missing comparator. Any external benchmark, if used, and its methods are not reported in the registry record.

Enrollment is listed as 6, but the number of participants assessed at 24 weeks, completing follow-up, or included in each analysis is not reported. The registry also does not describe how missing assessments, unconfirmed responses, treatment discontinuation, or unevaluable scans were handled. These omissions limit assessment of potential bias and the meaning of the endpoint denominator.

The trial is marked terminated, but the reason is not reported in the registry record. The recorded completion date does not explain the circumstances of termination. The record does not provide further details about treatment exposure, dose modifications, adherence, or participant characteristics that could help contextualize the results.

Safety interpretation is also limited. The record lists serious and other adverse event counts, serious event terms, and 4 deaths, but does not report the timing, causal attribution, event-level detail, or death causes. Analysis methods for the listed secondary outcomes, multiplicity procedures, and sample-size justification are not reported in the registry record. Together, these gaps prevent a complete evaluation of efficacy, precision, comparative effects, and safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation — NCT04390243.
• Registry record last updated 2024-05-06; status last verified 2023-09.
• Results first posted 2024-01-23.
• 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

NCT04390243 is a phase II, single-group trial sponsored by Academic and Community Cancer Research United. It enrolled 6 and is listed as terminated. The recorded start date is 2020-11-16, and the primary completion date is 2023-11-01. The reason for termination is not reported in the registry record.

The intervention is binimetinib plus encorafenib for pancreatic malignancies with a somatic BRAF V600E mutation. The primary endpoint is objective response rate at 24 weeks, defined using a confirmed complete or partial response assessed with RECIST version 1.1. The registry record does not report the primary endpoint result or its 95% confidence interval.

Secondary outcomes include progression-free survival, overall survival, duration of response, time to response, and Grade 3+ adverse events. No analysis entries are listed. Safety information includes one participant with a serious adverse event among six at risk, six with other adverse events among six at risk, and 4 deaths. Event attribution and the cause of death are not reported in the registry record.