MEK162 for Patients With RAS/RAF/MEK Activated Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MEK162 for Patients With RAS/RAF/MEK Activated Tumors (NCT01885195), a na phase 2 study. The primary outcome is Clinical Benefit Rate (CBR) for Solid Tumors at Week 16 as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.

2. Clinical Question

3. Trial Design

This was a completed, single-group Phase II study of MEK162 for patients with RAS/RAF/MEK-activated tumors. The study title describes a modular trial linking targeted therapy to tumors with pathway activation. Its stated purpose was signal seeking: to determine whether MEK162 showed sufficient efficacy in selected pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

The registry lists an enrollment of 110 and records Pfizer as the sponsor. The study start date is 2013-10-10, and the primary completion date is 2015-10-01. The status is COMPLETED. The intervention is MEK162, with a recorded dose of 45 mg twice daily on a continuous schedule.

The primary endpoint applies to solid tumors and measures clinical benefit at Week 16 using RECIST version 1.1. The listed secondary outcomes include response rates for solid tumors and for multiple myeloma and acute myeloid leukemia, progression-free survival, overall survival, duration of response, and treatment-emergent adverse events. The record also lists vital-sign abnormalities at or above Grade 3. These outcomes cover different tumor groups and different kinds of benefit and harm; the primary endpoint should not be treated as a summary of all of them.

Because the design is single group and allocation is NA, there is no randomized control arm. Findings from the treated group can describe outcomes during the study, but they cannot by themselves separate treatment effects from other explanations for those outcomes. The registry record does not report a protocol-level sample-size justification, detailed schedule of assessments, or an account of interim analyses.

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: Participants diagnosed with select solid tumors or hematological malignancies pre-identified (prior to study consent) and had an activation of the v-raf murine sarcoma viral oncogene (RAF)/ RAS oncogene \[rat sarcoma viral oncogene homologue\] (RAS)/mitogen-activated erk kinase (MEK) pathway and whose disease had progressed on or after standard treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set included all the participants who had received at least 1 dose of study drug. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

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: Full analysis set included all participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Benefit Rate (CBR) for Solid Tumors at Week 16 as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, measured over Week 16.

The primary endpoint is the clinical benefit rate for solid tumors at Week 16, assessed according to RECIST version 1.1. It counts participants with a complete response, partial response, or stable disease lasting at least 16 weeks. The endpoint is expressed as a percentage of participants, with a 95% confidence interval specified as the measure of uncertainty.

These response categories distinguish tumor disappearance or shrinkage from a period without sufficient change to meet the criteria for either response or progression. Complete response requires disappearance of target and non-target lesions, normalization of tumor marker level, and the specified lymph-node criterion. Partial response requires at least a 30% decrease in the sum of target-lesion diameters relative to baseline. Stable disease means neither sufficient shrinkage for partial response nor sufficient increase for progressive disease, using the smallest sum of diameters as the reference. Progressive disease includes the specified increase in target-lesion diameters, unequivocal progression of existing non-target lesions, or appearance of new lesions.

A clinical benefit endpoint combines response with sustained stable disease, so it captures more than tumor shrinkage alone. Its fixed Week 16 time point also makes the duration requirement part of the outcome definition. Interpretation depends on both the number meeting these criteria and the number evaluable for the endpoint. Neither the numerical clinical benefit rate nor its confidence interval is reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a percentage estimate?

For a binary outcome such as meeting or not meeting a clinical benefit definition, the percentage is the proportion of participants classified as having the event among those analyzed. Here, the event is meeting one of the specified response categories, with stable disease required to last at least 16 weeks. The relevant denominator is the evaluable population for this endpoint, not automatically everyone enrolled or everyone who received treatment. The registry says the full analysis set included participants who received at least 1 dose, and clarifies that the stated analyzed number for this outcome means participants evaluable for it. The actual endpoint denominator is not reported in the registry record.

What does a confidence interval add?

A confidence interval expresses statistical uncertainty around an estimate. It helps readers judge whether a reported percentage is precise or compatible with a broader range of values. It does not correct for limitations in study design, missing outcome data, or differences between the study population and other populations. The registry specifies a 95% confidence interval for the primary percentage, but neither the estimate nor the interval bounds are reported in the registry record. Precision therefore cannot be evaluated from the available endpoint record.

Why does the endpoint definition matter?

RECIST version 1.1 supplies operational rules for classifying tumor response and progression. Operational definitions aim to make outcome classification more consistent by specifying how lesion measurements are interpreted. In this study, clinical benefit includes complete response, partial response, or stable disease maintained for the stated duration. Consequently, the endpoint combines distinct outcome states rather than measuring a single degree of tumor shrinkage. A percentage for the composite would not identify the contribution of each state unless those component results were also reported.

The criteria distinguish changes in target lesions, non-target lesions, tumor markers, lymph nodes, and new lesions. Complete response requires disappearance of lesions and the specified additional conditions. Partial response requires at least a 30% decrease in the sum of target-lesion diameters from baseline. Stable disease is defined by not meeting the response or progression thresholds, using the smallest sum of diameters as reference. Progressive disease includes at least a 20% increase in target-lesion diameter sum with the stated absolute increase, unequivocal progression of existing non-target lesions, or new lesions. These rules explain what is classified; they do not supply the study’s observed result.

Why does a single-group design limit comparison?

A single-group study can describe the outcomes observed among treated participants. It does not include a randomized concurrent control group, so it cannot estimate a treatment-versus-control contrast under the same allocation process. Comparisons with historical expectations or other studies would require additional information and assumptions; such comparisons are not reported in the registry record. The study’s stated signal-seeking purpose should therefore be kept distinct from a confirmatory claim of comparative efficacy.

How should planning calculations be understood?

General sample-size calculations depend on assumptions about the outcome to detect, the significance level, allocation, and statistical approximation. The planning assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of the observed effect. They are described as planning illustrations, not as the trial’s own design. The observed effect and numerical planning outputs are not reported in the registry record, so no numerical planning conclusion can be drawn from those assumptions alone. Planning sample sizes are not observed power and do not describe the probability that this completed study produced a significant result.

For event counts that use time-to-event methods, the planning note describes total events; for other outcomes, it describes participants per arm. Those are different quantities and should not be interchanged. The actual trial design remains single group, so hypothetical equal-allocation calculations do not create a comparator or change how the study was conducted.

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("Binimetinib (MEK162)")
n      <- c(104)
events <- c(24)
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  Binimetinib (MEK162)  104  24  23.1  15.4  32.4  16.0  32.0  16.0  32.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary solid-tumor clinical benefit endpoint and secondary outcomes covering response, survival, duration of response, and safety. When several outcomes are examined, the chance of at least one apparently unusual result can increase if each is interpreted separately without accounting for the number of comparisons. General approaches to multiplicity include prespecifying a primary outcome, adjusting inferential thresholds, or treating secondary findings as exploratory. The registry record does not report a multiplicity adjustment or a detailed hierarchy for interpreting the outcomes.

The registry record lists 0 analyses. This does not supply an analysis plan or explain how outcomes were selected, modeled, or reported. The numerical result for the primary endpoint and the secondary outcomes is not reported in the registry record, so the effect of any multiplicity approach cannot be assessed.

The primary endpoint description says that the full analysis set included participants who received at least 1 dose of study drug, and that the number analyzed for this outcome means participants evaluable for it. These statements do not establish how many participants were evaluable, how missing assessments were handled, or whether participants without an evaluable Week 16 assessment were excluded, imputed, or classified in another way. The method for handling missing data is not reported in the registry record.

These details matter because the percentage can depend on who enters the denominator and how missing outcomes are treated. The denominator, missing-data method, and sensitivity analyses are not reported in the registry record. Readers should therefore distinguish the stated endpoint definition from the unreported analysis decisions needed to reproduce its estimate.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: dyspnoea (10.9%), abdominal pain (3.6%), small intestinal obstruction (3.6%), dehydration (3.6%), pneumonia (2.7%).

The registry lists serious adverse event terms with percentages: dyspnoea, 10.9%; abdominal pain, 3.6%; small intestinal obstruction, 3.6%; dehydration, 3.6%; pneumonia, 2.7%; and urinary tract infection, 2.7%. It records 110 participants at risk and 50 affected for serious adverse events in the MEK162 group. The registry record does not provide the numerical primary efficacy result in the same record details.

These terms describe safety events, not the clinical benefit endpoint. A listed percentage is not a measure of treatment benefit, and event percentages should not be combined to create an overall rate: a participant may experience more than one type of event. The listed terms are only the terms identified in the record, and their percentages do not describe every possible safety outcome. The registry also lists treatment-emergent adverse events and vital-sign abnormalities as outcomes, but their numerical results are not reported in the registry record.

Safety counts and percentages describe events observed in the study group. With no randomized control group, they do not establish how often the same events would have occurred under another treatment or without study treatment. The record’s serious-event figures should therefore be read as descriptive safety information from this single-group study, not as a comparative estimate.

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

The registry record establishes that the study examined MEK162 in a signal-seeking, single-group Phase II setting and defined a primary endpoint for solid tumors. It gives the endpoint’s criteria, time point, and intended uncertainty measure. It does not report the numerical clinical benefit rate, confidence interval, or evaluable denominator. Consequently, the endpoint’s observed level and precision cannot be assessed from the registry record.

Even if the numerical endpoint were available, its meaning would remain specific to the enrolled study population, the RECIST version 1.1 criteria, the Week 16 assessment, and the rule that stable disease must persist for at least 16 weeks. A composite clinical benefit percentage would not by itself show the separate frequencies of complete response, partial response, and stable disease. The registry lists other outcomes, but their numerical results are not reported in the registry record.

The design also limits what can be concluded. Because the study has one group and no randomized comparator, outcomes observed among participants cannot be interpreted as a controlled estimate of the effect of MEK162. This distinction applies whether a result appears favorable, unfavorable, or uncertain. The record’s stated aim was to assess a signal that might warrant further study; it does not provide a randomized comparison or a basis for causal attribution.

The serious adverse event figures provide descriptive information for the treated group, but they do not quantify comparative safety. Nor do the listed event terms represent every safety outcome in the study. The registry’s listed secondary outcomes indicate what was intended to be assessed, not what those outcomes showed.

In short, the registry record explains the study question and measurement framework, but does not report the numerical primary outcome needed to characterize the observed clinical benefit. It also leaves the analysis denominator, missing-data handling, and detailed statistical plan unreported. Those limits should guide any interpretation of the study record.

14. Why This Trial Matters Statistically

This trial illustrates a common statistical distinction between defining an outcome and reporting its result. A detailed endpoint definition can make clear what qualifies as clinical benefit, yet it cannot show the observed frequency or the precision of that frequency when the estimate and interval are absent. For this study, the Week 16 endpoint is explicitly defined, while its numerical value is not reported in the registry record.

It also highlights why denominators matter. The record distinguishes participants who received at least 1 dose from those evaluable for the primary outcome. Those populations need not be interchangeable. Without the evaluable denominator and a description of missing assessments, readers cannot reconstruct or fully assess a percentage estimate.

The single-group design is another important teaching point. Descriptive results can characterize outcomes within a treated group, but a randomized comparison is needed to estimate a contrast protected by random allocation. The study’s signal-seeking purpose is relevant context, but it does not remove the distinction between a within-group observation and a comparative treatment effect.

Finally, the record lists multiple outcome domains, including response, survival, and safety. Multiple outcomes call for a clear analysis strategy and cautious interpretation, especially when numerical estimates and multiplicity procedures are unavailable. The case therefore shows how endpoint definitions, analysis populations, uncertainty, design, and reporting completeness jointly shape what clinical trial statistics can support.

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 interpreting efficacy from the registry record is that it does not report the clinical benefit rate or its 95% confidence interval. The endpoint denominator is also not reported. Although the record explains that the analyzed number refers to participants evaluable for the endpoint, it does not give that number or describe how missing assessments were handled.

The study is single group, with allocation recorded as NA. There is no randomized control group for a like-for-like comparison, so the design cannot provide a randomized estimate of treatment effect. The signal-seeking objective should be understood in that context rather than as evidence of a comparative result.

The clinical benefit endpoint combines complete response, partial response, and sustained stable disease. The record does not report the numerical contribution of each category. Outcomes for the listed hematologic groups and secondary outcomes are also not numerically reported in the registry record. Thus, the primary endpoint definition cannot stand in for the missing results across these separate outcome domains.

The registry record does not report a detailed statistical analysis plan, a multiplicity adjustment, a missing-data method, sensitivity analyses, or the rationale for the enrollment target. It also does not report interim-analysis procedures. These omissions limit assessment of how the outcomes were analyzed and how robust any estimate might be. The serious adverse event terms are descriptive and do not provide a randomized safety comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: MEK162 for Patients With RAS/RAF/MEK Activated Tumors — NCT01885195.
• Registry record last updated 2021-02-21; status last verified 2021-02.
• Results first posted 2021-02-21.
• 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

NCT01885195 is a completed, single-group Phase II study of MEK162 for RAS/RAF/MEK-activated tumors. The registry records an enrollment of 110, Pfizer as sponsor, a start date of 2013-10-10, and a primary completion date of 2015-10-01. The recorded regimen is 45 mg twice daily on a continuous schedule.

The primary endpoint is clinical benefit rate for solid tumors at Week 16 by RECIST version 1.1, defined as complete response, partial response, or stable disease lasting at least 16 weeks. The registry specifies a 95% confidence interval, but the endpoint estimate, interval, and evaluable denominator are not reported in the registry record. The single-group design has no randomized comparator, and the registry does not report the detailed analysis or missing-data methods.