Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors (NCT01927341), a non-randomized phase 1, phase 2 study. The primary outcome is Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2.

2. Clinical Question

The study addressed two different aims across its phases. The Phase Ib purpose was to estimate MTD/RPD2, while the Phase II purpose was to assess anti-tumor activity of the combination. The Phase II response endpoint therefore asks how often participants had a qualifying tumor response during treatment, not whether the combination outperformed another treatment.

The study record reports 53 participants enrolled overall. The Phase II cohorts separate participants by tumor RAS status and prior EGFR-inhibitor exposure, characteristics that define different clinical groups in the registry. Since treatment assignment was not randomized and no comparator is listed, any differences between cohorts would not constitute a randomized treatment contrast. The record does not report a result for the primary endpoint, so the clinical question cannot be answered from the posted primary-outcome information.

3. Trial Design

This completed study is recorded as Phase Ib and Phase II, open-label, multi-center, non-randomized, and single-group. Its title describes dose escalation of MEK162 with panitumumab in adults with mutant or wild-type RAS metastatic colorectal cancer. The registry lists Pfizer as sponsor, an enrollment of 53, a start date of 2013-11-19, and a primary completion date of 2016-01-25.

Phase Ib is described as dose escalation. The stated primary purpose for that phase was to estimate MTD/RPD2. The registry does not report the dose-escalation procedure, dose levels, stopping rules, or an estimate of MTD/RPD2. Those design details should not be inferred from the phase label alone.

Phase II is divided into four RAS and treatment-history groups. These are mutant RAS disease without prior EGFR inhibitor treatment; acquired mutant RAS disease after anti-EGFR monoclonal antibody therapy but without prior EGFR tyrosine kinase inhibitor therapy; wild-type RAS disease after EGFR-inhibitor treatment; and wild-type RAS disease without prior EGFR-inhibitor treatment. The record describes the EGFR-inhibitor history as including tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy where applicable.

Because the study is non-randomized and single-group, the cohorts are not like-for-like control arms. They differ by tumor and treatment-history characteristics, and the record does not describe random assignment or a concurrent standard-treatment comparator. Open-label status means masking is listed as none. The record does not report further details about assessment procedures intended to limit bias.

The registry lists MEK162 and panitumumab as interventions. The adverse-event cohort labels use the name binimetinib plus panitumumab. The registry record does not explain this naming difference, so it is safest to preserve the wording used for each part of the record rather than assume how the names relate.

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: The study used binimetinib 45 mg twice a day (BID) and panitumumab 6 mg/kg intravenous infusion once every second week without planned dose escalation.

Phase 1b

Reasons for not completing this period:

Phase 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Dose determining set included all phase 1b participants who received at least 1 dose of binimetinib or panitumumab and had at least 1 valid post baseline safety assessment, and those who had either experienced a DLT at any time during Cycle 1 or had met the following minimum treatment and safety evaluation requirements without experiencing a DLT during Cycle 1.

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 full or partial dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2, measured over From the start of the treatment until CR or PR (approximately up to 11 months).

The Phase II primary endpoint is overall response rate (ORR), defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) under RECIST version 1.1, based on local radiology assessment. The assessment period is from the start of treatment until CR or PR, approximately up to 11 months.

In the registry definition, CR requires disappearance of all non-nodal target lesions and all non-target lesions, with pathological lymph nodes assigned as target or non-target lesions reduced to a short axis under 10 mm. PR requires at least a 30 percent decrease in the sum of target-lesion diameters, using the baseline sum as the reference. These criteria turn changes in tumor measurements into a prespecified categorical response outcome.

General statistical context: a response percentage is a concise summary of how many participants in an analysis population met the response definition. It is useful for describing observed tumor shrinkage according to the stated criteria, but it does not by itself establish that treatment caused the responses. A comparator and an appropriate design are needed to estimate a treatment contrast. The record defines a full analysis set as participants who received at least 1 full or partial dose of study drug, but it does not post the Phase II ORR value or its uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an open-label, non-randomized, single-group Phase Ib/II study. These design labels matter for interpretation: they identify how participants were assigned and whether treatment masking was used. They do not, on their own, specify the statistical analysis plan. The registry record does not report a detailed statistical plan for the Phase II response analysis.

What does ORR measure?

ORR is the percentage of participants whose best overall response was complete response or partial response under RECIST version 1.1. The registry specifies local radiology assessment and defines the response criteria. In general, a percentage is a proportion expressed on a 0-to-100 scale: its interpretation depends on the number of participants assessed and the response definition. The registry names a full analysis set of participants who received at least 1 full or partial dose of study drug, but does not state the number analyzed for the primary endpoint or provide the response count.

General statistical context: an estimate of a proportion is subject to sampling variability. A confidence interval expresses the range of values reasonably compatible with the observed data under the analysis assumptions. It communicates precision, not certainty that the true value lies within a particular interval. No confidence interval for ORR is reported in the registry record, so precision cannot be assessed.

Why does the study design matter?

In a randomized trial, random assignment is intended to balance measured and unmeasured participant characteristics across treatment groups on average. This study is explicitly non-randomized and single-group, and no separate comparator is listed. Its Phase II patient categories are cohorts distinguished by RAS status and prior EGFR-inhibitor exposure, not randomized control groups. General statistical context: comparisons between non-randomized cohorts can reflect differences in prognosis, prior therapy, or other participant characteristics as well as treatment response. Such comparisons should not be interpreted as randomized treatment effects.

The study is also open-label, with masking listed as none. The primary response endpoint uses local radiology assessment. General statistical context: a clearly defined response rule improves consistency, while knowledge of treatment can still be relevant to assessment and other trial processes. The registry does not report whether any independent assessment was used, so that cannot be assumed.

What can the adverse-event counts establish?

The record lists, for each adverse-event group, the number at risk and the number affected for serious adverse events and for other adverse events. These are participant counts, not estimates comparing randomized treatments. General statistical context: event counts are most interpretable alongside their denominators, follow-up period, event definitions, and method of collection. The registry gives group-specific at-risk counts, but does not provide a detailed safety analysis plan, exposure-adjusted rates, or a comparator. It also does not report death counts in the death entries.

The serious-event term list includes Small Intestinal Obstruction, Septic Shock, Deep Vein Thrombosis, Hypovolaemic Shock, Diarrhoea, and Anaemia, each with a percentage. The registry record does not identify the denominator used for these percentages or explain whether the entries represent participants, events, or another summary. They should therefore be read as listed terms and percentages rather than used to infer a specific risk in the whole study population.

How should sample-size illustrations be understood?

The stated sample-size assumptions describe a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is a stated fraction of the observed effect. The record specifies that non-time-to-event illustrations use participants per arm, while time-to-event illustrations use total events under the Schoenfeld method.

General statistical context: these assumptions describe a hypothetical planning exercise, not a report of the original trial's design or an observed power calculation. The registry record does not report the original sample-size justification. It also contains no posted primary response estimate from which to interpret an observed-effect-based illustration. The number of participants per arm for 80% power or any other planning output is not reported in the registry record. No planned sample-size figure should be inferred from the enrollment of 53.

What analysis information is missing?

The registry record lists 11 outcome measures and no analysis records. It does not report hypothesis tests, confidence intervals, covariate adjustments, handling of missing endpoint assessments, or a multiplicity strategy. General statistical context: these choices affect how estimates and tests should be interpreted, especially when multiple endpoints or cohorts are considered. Without a stated analysis plan and posted results, those methods cannot be reconstructed responsibly.

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("Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Pan", "Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Pani", "Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumu", "Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitum")
n      <- c(15, 5, 15, 8)
events <- c(0, 0, 1, 0)
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  Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Pan  15  0  0.0  0.0  21.8  0.0  20.4  0.2  20.6
ARM  Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Pani  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9
ARM  Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumu  15  1  6.7  0.2  31.9  1.2  29.8  1.6  30.2
ARM  Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitum  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the Phase II primary ORR, safety outcomes, and several additional tumor outcomes. It lists no analysis records. The registry record does not report whether hypotheses were tested across multiple outcomes, whether any adjustment for multiplicity was planned, or how the primary endpoint analysis was prioritized relative to secondary outcomes.

General statistical context: when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis strategy accounts for the number and relationship of tests. This concern is particularly relevant when results are reported across multiple endpoints or subgroups. The existence of multiple registered outcomes does not by itself establish that formal tests were conducted, and no such tests are posted in the record.

The record defines the full analysis set as participants who received at least 1 full or partial dose of study drug. It does not report the number included in the primary endpoint analysis, the number with missing response assessments, or how missing or unevaluable assessments were handled. It also does not report whether the analysis population differed across outcomes or cohorts. Those details are important for understanding the denominator and potential selection in a response percentage.

The sample-size assumptions describe a planning illustration using an observed effect, but the original sample-size justification is not reported in the registry record. The record also does not report interim analyses or stopping rules. These omissions do not establish that such procedures were absent; they mean they are not described in the registry record. No multiplicity-adjusted or missing-data method can therefore be attributed to the study based on the posted information.

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: small intestinal obstruction (20.0%), septic shock (20.0%), deep vein thrombosis (20.0%), hypovolaemic shock (20.0%), diarrhoea (13.3%).

The adverse-event information is presented by five groups: Phase Ib, and four Phase II cohorts classified by RAS status and prior EGFR-inhibitor treatment. The registry reports the number at risk and the number affected for serious adverse events and for other adverse events. These counts should be read within each named group; they are not randomized comparisons.

For serious adverse events, the recorded at-risk and affected counts are 10 and 3 for Phase Ib; 15 and 6 for mutant RAS EGFRi-naive Phase II; 5 and 2 for mutant RAS anti-EGFRi Phase II; 15 and 9 for wild-type RAS anti-EGFRi Phase II; and 8 and 5 for wild-type RAS EGFRi-naive Phase II. The record also lists other adverse-event counts of 10 of 10, 15 of 15, 5 of 5, 15 of 15, and 8 of 8, respectively.

The serious-event term list names Small Intestinal Obstruction, Septic Shock, Deep Vein Thrombosis, and Hypovolaemic Shock at 20.0% each, Diarrhoea at 13.3%, and Anaemia at 12.5%. The denominator for these percentages is not reported in the registry record, so they should not be treated as whole-study incidence estimates. Death counts are not reported in the registry record. The counts do not establish comparative risk or causality.

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

The record establishes the study's stated objectives and the framework for assessing Phase II anti-tumor activity. It identifies ORR as the primary Phase II endpoint, defines complete and partial response using RECIST version 1.1, and specifies local radiology assessment. It also records participant counts for adverse-event categories in the listed cohorts.

However, the registry record does not report the primary ORR result, the response count, or a confidence interval. It does not report analyses for the other registered outcomes. Accordingly, the posted information cannot show the size or precision of the observed response proportion. An unreported result must not be read as no responses or no effect.

The design also does not include a randomized comparator. General statistical context: an outcome observed in a single-group study describes what happened among participants receiving the study treatment, but cannot establish what would have happened to comparable participants under another treatment or no treatment. Cohort differences based on RAS status and prior treatment do not supply that missing counterfactual because these groups were not randomized to treatment strategies.

The adverse-event counts indicate that serious adverse events were recorded among participants in each listed group, and the record names several serious-event terms with percentages. These entries do not by themselves establish that treatment caused an event, quantify comparative risk, or characterize the full safety profile. The percentages' denominator and death counts are not reported in the registry record.

Thus, the record is informative about the study's design, registered endpoint, cohort definitions, and selected safety counts. It is not sufficient to determine whether a particular response rate was observed, how precise it was, whether outcomes differed across groups, or how treatment compared with an alternative. Those conclusions require posted outcome analyses and, for comparative effects, an appropriate comparator design.

14. Why This Trial Matters Statistically

This study illustrates why a trial's design and its posted results need to be read together. The registry identifies a Phase Ib dose-escalation component and a Phase II anti-tumor activity component, but the primary Phase II response result is not reported. Knowing the endpoint definition is useful, yet it cannot substitute for the estimate, denominator, and uncertainty needed to interpret an outcome.

The cohort structure also illustrates the distinction between stratified description and controlled comparison. The Phase II cohorts group patients by RAS status and prior EGFR-inhibitor exposure. These details help define the populations addressed by the study, but the non-randomized, single-group design does not make the cohorts exchangeable treatment arms. Differences across them could reflect their differing clinical characteristics rather than treatment effects.

Statistically, the record also provides a useful reminder that safety counts and percentages require context. Group-specific denominators are listed, but the denominator for the serious-event term percentages is not. Without that information, those percentages cannot safely be interpreted as incidence in the overall study population. The null death entries likewise do not provide death counts.

Finally, the registry lists numerous outcome measures but no analysis records. That gap makes it impossible to assess reported uncertainty, missing-data handling, multiplicity, or the statistical treatment of subgroup results. These are not details that can be reconstructed from the study title or endpoint labels. The record therefore demonstrates the difference between an endpoint being registered and an analysis being available for statistical interpretation.

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 interpretation is that the registry record does not post the Phase II primary ORR result or its analysis. No response count, denominator for the endpoint, confidence interval, or test result is reported. Without these, neither the response magnitude nor its precision can be assessed.

The study is non-randomized, open-label, and single-group, and no separate comparator is listed. Consequently, any observed outcome would be descriptive rather than a randomized estimate of comparative treatment effect. The Phase II cohorts also differ by RAS status and prior EGFR-inhibitor exposure, so they should not be treated as interchangeable control groups.

The record gives an overall enrollment of 53, but does not report the number analyzed for the primary outcome or the number with missing or unevaluable response assessments. It does not state how such cases were handled. Although the full analysis set is defined by receipt of at least 1 full or partial dose, the endpoint-specific denominator is not reported.

Further details not reported in the registry record include the original sample-size justification, the Phase Ib dose-escalation method and result, the statistical analysis plan, multiplicity procedures, interim analyses, stopping rules, and the use of any independent response assessment. Safety interpretation is constrained by the absence of a comparator, the lack of a reported denominator for serious-event term percentages, and unreported death counts. The adverse-event group labels use binimetinib, while the intervention listing uses MEK162; the registry record does not explain the naming difference.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors — NCT01927341.
• Registry record last updated 2021-02-18; status last verified 2021-01.
• Results first posted 2021-02-18.
• 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, open-label, non-randomized, single-group Phase Ib/II study of MEK162 with panitumumab in adults with metastatic colorectal cancer. It reports an enrollment of 53 and includes Phase II cohorts defined by RAS status and prior EGFR-inhibitor treatment.

The Phase II primary endpoint is ORR by RECIST version 1.1, assessed by local radiology, with the response period described as approximately up to 11 months. The registry record does not report the primary endpoint result or any analysis records. It lists safety counts for five groups and serious-event terms with percentages, but the denominator for those percentages is not reported. The posted information therefore supports description of the design and registered measures, but not a conclusion about the magnitude or precision of Phase II response.