Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET (NCT02544633), a non-randomized phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The question is about observed tumor response in a selected population with MET alterations, not about a randomized comparison of MGCD265 with another treatment. The four arms distinguish tumor-tissue findings from ctDNA findings and MET activating mutations from MET gene amplifications. Those groups are not interchangeable control groups: allocation was non-randomized, and the registry does not report a like-for-like comparator.

The planned primary measure is objective response rate, a proportion based on confirmed complete or partial responses. The registry identifies the modified Intent-to-Treat population as patients who received at least one dose. The total enrollment is reported as 68, but the number analyzed for the primary endpoint is not reported in the registry record. Enrollment and the primary analysis population therefore should not be assumed to be identical.

3. Trial Design

This was a Phase 2, parallel-arm study with non-randomized allocation and no masking. It evaluated MGCD265 in patients with non-small cell lung cancer and activating genetic alterations in MET. The registry reports enrollment of 68 and a completed study. The recorded start was 2015-10, and primary completion was 2018-04-30.

The four arms were defined by the source and type of MET finding: activating mutations in tumor tissue, gene amplifications in tumor tissue, activating mutations in ctDNA, and gene amplifications in ctDNA. All arms received MGCD265; the record does not describe a placebo or active control arm. As allocation was not randomized, differences between these groups cannot be interpreted as treatment effects of one group versus another. The registry does not report how assignment among the arms was determined.

The summary describes MGCD265 as an oral receptor tyrosine kinase inhibitor targeting MET and other receptors, taken twice daily. Patients had locally advanced, unresectable or metastatic disease, and previous chemotherapy was required. The registry describes testing for MET alterations in either tumor tissue or blood samples.

The study summary says that the number of patients to be enrolled would depend on how many enrolled patients experienced tumor size reduction. The registry record does not report further details about that enrollment approach, a sample-size justification, or the statistical design behind it. It also does not report whether interim analyses were planned or conducted. These details should not be inferred from the Phase 2 designation or from the listed enrollment.

The primary endpoint was objective response rate, assessed by investigators using RECIST 1.1 and measured up to 3 months. Secondary outcomes included duration of response, progression-free survival, one-year survival rate, overall survival, treatment-emergent adverse events, and plasma concentration measures for MGCD265. The registry lists 17 outcome measures and 4 analyses, but does not identify the analysis methods for each measure in the information available for this description.

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: Sponsor approval of each potential patient's genetic testing following prescreening, whether performed by the study central lab or a Sponsor-approved local lab, was filed prior to proceeding to full clinical screening. All patients considered eligible for the study following clinical screening were submitted to Sponsor for registration approval.

Treatment Period

Reasons for not completing this period:

Survival Follow-up Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat (mITT) Population defined as all patients who received at least one dose of MGCD265

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: These figures are based on the safety population.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate, measured over Up to 3 months.

The primary endpoint is objective response rate: the percentage of patients with a confirmed complete response or partial response, based on investigator assessment under RECIST 1.1. The assessment timeframe is up to 3 months, and the defined analysis population is the modified Intent-to-Treat population, consisting of patients who received at least one dose of MGCD265.

RECIST 1.1 classifies tumor response using changes in target and non-target lesions assessed by CT or MRI. A complete response requires disappearance of all target lesions, with an exception for nodal disease. A partial response requires at least a 30% decrease from baseline in the sum of diameters of target measurable lesions. Stable disease is a response that does not meet the criteria for complete response, partial response or progression. Progressive disease includes a 20% increase above the smallest observed sum of target lesion diameters, with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions.

Objective response is used to describe whether tumor shrinkage meeting specified criteria was documented. It is a proportion, not a measure of how long response lasts or whether it changes survival; duration of response and survival outcomes are listed separately as secondary outcomes. A confirmed response also depends on the study’s assessment and confirmation procedures. The registry gives the endpoint definition but does not report the observed response percentage, its confidence interval, or the number included in that endpoint analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a percentage endpoint and a 95% confidence interval. The statistical concepts below are general explanations; the analysis choices actually used in this study are not fully reported in the registry record.

What does a response percentage describe?

A response percentage is a proportion: the number of patients meeting the response definition relative to the number assessed in the analysis population. For this study, a response required a confirmed complete or partial response under RECIST 1.1. The intended population is defined as patients who received at least one dose of MGCD265. The record does not give the response count, the number analyzed, or the resulting percentage. Without those values, the endpoint cannot be independently checked or interpreted quantitatively.

A proportion depends on its denominator. If some patients do not have a usable endpoint assessment, the handling of those patients can affect the estimated response percentage. For example, a protocol may define how to treat missing assessments or early discontinuations, but the registry record does not report such rules. It is also not reported whether the response assessment was reviewed independently or only by investigators; the endpoint description specifies investigator assessment.

What does a confidence interval add?

In general, a confidence interval describes statistical uncertainty around an estimate. For a response percentage, it indicates a range of values compatible with the observed data under the interval method’s assumptions. A wider interval indicates less precision, while a narrower interval indicates greater precision. The registry specifies a 95% confidence interval as the dispersion measure but does not report the interval limits or the method used to calculate it. The confidence level alone cannot show whether the estimate is precise.

A confidence interval is not a guarantee that the true response percentage lies within its limits, and it does not by itself establish a treatment effect. Interpretation also depends on the study design, outcome definition, analysis population and possible sources of bias. In this study, the lack of a randomized comparator means that a response estimate, even if reported, would be descriptive of the treated population unless a valid comparison is separately established.

Why does the non-randomized design matter?

Randomization is a general design method for balancing measured and unmeasured patient characteristics across treatment groups, on average. This study is explicitly non-randomized and has no masking. Its parallel arms classify patients by alteration type and source of testing; they are not like-for-like controls. Comparisons across those groups could be confounded by patient or disease differences. The registry does not report an adjustment strategy that would address such differences.

Masking is intended in general to reduce the influence of treatment knowledge on assessments or reporting. Since masking is listed as none and response is based on investigator assessment, assessment could be influenced by knowledge of treatment or other study context. This is a methodological consideration, not evidence that any assessment was biased. The record does not describe blinded review procedures.

What is the role of sample-size planning?

General sample-size planning estimates how much information a study may need to detect a specified effect under chosen assumptions. The planning illustrations associated with the study use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For time-to-event outcomes, the stated illustration is based on the total number of events; other illustrations refer to participants per arm. These are planning illustrations based on the observed effect, not the trial’s own design justification and not observed power.

The registry does not report the actual sample-size calculation used to plan this trial, its target effect, or its rationale. The summary says enrollment would depend on the number of patients experiencing tumor size reduction, but does not provide further methodological detail. No sample-size illustration values are reported in the record, so none can be compared with enrollment.

What can secondary outcomes contribute?

Duration of response, progression-free survival, one-year survival rate and overall survival address outcomes different from whether a confirmed response occurred. Time-to-event outcomes generally describe the time until a specified event, with methods that account for differing follow-up and censoring. The registry lists these outcomes but does not provide their results, definitions in detail, follow-up information, or statistical methods. Plasma concentration measures describe drug exposure, while adverse event outcomes describe safety events; neither answers the primary response question directly.

Overall, the record identifies several statistical ingredients—the response definition, analysis population, timeframe and confidence-interval level—but does not report the numerical efficacy estimate or enough analysis details to reproduce it. General statistical principles can clarify what such information would mean, but they cannot replace the missing study-specific results.

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("MET Activating Mutations in Tumor Tissue", "MET Gene Amplifications in Tumor Tissue", "MET Activating Mutations in ctDNA", "MET Gene Amplifications in ctDNA")
n      <- c(28, 20, 8, 12)
events <- c(3, 3, 2, 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  MET Activating Mutations in Tumor Tissue  28  3  10.7  2.3  28.2  3.7  27.2  3.9  27.4
ARM  MET Gene Amplifications in Tumor Tissue  20  3  15.0  3.2  37.9  5.2  36.0  5.4  36.3
ARM  MET Activating Mutations in ctDNA  8  2  25.0  3.2  65.1  7.1  59.1  7.5  60.0
ARM  MET Gene Amplifications in ctDNA  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures and 4 analyses. Multiple outcomes and analyses can create a multiplicity issue: when many statistical questions are examined, the chance of at least one apparently notable result can increase. General approaches include prespecifying a primary analysis, adjusting for multiple comparisons, or interpreting secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or which of the listed analyses were confirmatory.

The primary endpoint is identified as objective response rate, with a 95% confidence interval, but the registry record does not report a p-value, a testing procedure, or the numerical result. It also does not report whether any interim analyses were planned or performed. These details should not be inferred from the number of outcome measures or the Phase 2 designation.

The primary population is defined as patients who received at least one dose of MGCD265. The record does not report the number in that population or the number with an evaluable response assessment. It does not describe the treatment of missing or unevaluable response data, withdrawals, or patients without confirmation. Those omissions matter because different handling rules can change the denominator and estimate.

The total enrollment is 68, but that figure should not be substituted for the primary analysis denominator without confirmation. The record does not report how many enrolled patients received treatment or contributed to each secondary outcome. It also does not report imputation methods, sensitivity analyses for missing data, or analysis-population definitions for the secondary outcomes. As a result, the completeness and robustness of the endpoint analyses cannot be assessed from the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: malignant neoplasm progression (33.3%), dehydration (25.0%), pneumonia (15.0%), nausea (12.5%), vomiting (12.5%).

The registry reports serious adverse event figures by the four MET alteration groups and in total. In the total group, 33 affected are listed among 68 at risk for serious adverse events. The group figures are 12 among 28 for mutations in tumor tissue, 10 among 20 for amplifications in tumor tissue, 4 among 8 for mutations in ctDNA, and 7 among 12 for amplifications in ctDNA. The record also lists 67 affected among 68 at risk for other adverse events in total. These are descriptive registry figures, not randomized comparisons.

The record lists deaths as 38 in total, with group figures of 12, 14, 3 and 9 in the same group order. It does not provide enough information in the available record to interpret these figures as caused by MGCD265. The listed serious adverse event terms are malignant neoplasm progression at 33.3%, dehydration at 25.0%, pneumonia at 15.0%, nausea at 12.5%, vomiting at 12.5%, and lower respiratory tract infection at 12.5%. The denominator and method used for these term percentages are not reported in the registry record.

Serious and other adverse event categories should not be treated as mutually exclusive without further information: a patient may experience more than one event. The registry figures do not establish comparative risk against another treatment, and the record does not describe attribution or event-level timing. They should be read as reported safety counts and terms, not as evidence of causation or as a complete account of each patient’s experience.

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

The registry record establishes that a completed Phase 2 study evaluated MGCD265 in patients with non-small cell lung cancer and activating MET alterations. It defines a primary endpoint based on confirmed complete or partial response under RECIST 1.1, assessed by investigators up to 3 months. It also reports enrollment and descriptive safety figures.

The record does not report the observed objective response rate or its confidence interval. It therefore does not show the size or precision of the primary endpoint estimate, and it cannot answer from the posted information whether response was more frequent than an external expectation. A definition of an endpoint is not itself a result. The listed secondary outcomes also do not have reported results in the information available for this description.

The study had no randomized control group, and its arms were based on the MET alteration type and whether the finding came from tumor tissue or ctDNA. Consequently, the study design does not support treating differences among those groups as randomized treatment comparisons. The record also does not report a statistical adjustment that would make those groups comparable.

The safety figures provide counts for serious and other adverse events, deaths, and selected serious event terms. They do not, on their own, establish that MGCD265 caused an event, nor do they compare safety with another treatment. The term percentages have no reported denominator in the record.

In short, the registry supplies important definitions and design information but not the primary efficacy result or the analysis details needed to judge its precision and robustness. Statistical interpretation must remain limited to what is reported: study structure, outcome definitions, enrollment, and descriptive safety information. It cannot be extended into a conclusion about treatment benefit or lack of benefit.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between a clearly defined outcome and a reported outcome estimate. Objective response rate is defined using RECIST 1.1, an investigator assessment, a specified analysis population and a timeframe. Those details indicate what the endpoint is intended to measure. Yet without the observed percentage, confidence interval and analysis denominator, readers cannot assess the amount of response or its precision.

The non-randomized design also makes the study’s comparison question important. The registry summary refers to response relative to what might be expected with other available treatments, but it does not report a randomized comparator or a numerical external benchmark. Historical expectations can differ across populations, assessment methods and follow-up. The registry record does not describe a method for establishing or adjusting such a comparison, so it should not be assumed.

The four parallel groups make clear that alteration type and testing source are central to the study’s organization. They also illustrate why subgroup descriptions do not automatically provide fair comparisons. Without random allocation, patient characteristics may differ across groups, and any observed differences could have explanations other than the grouping variable or treatment.

The record additionally lists many outcome measures and analyses. That makes it important to know which analyses were prespecified, how multiplicity was handled, and how missing endpoint data were treated. Those statistical details are not reported in the registry record. Their absence limits assessment of how securely a result could be interpreted, even if a numerical estimate were available.

These points make the record valuable as a case study in reading registry information carefully: design, endpoint definition and result reporting answer different questions. Here, the first two are described in detail, while the primary efficacy result and important analysis details are not reported.

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 principal limitation for statistical interpretation is that the registry record does not report the primary objective response rate, its confidence interval, the response count, or the primary endpoint denominator. The endpoint definition is detailed, but it is not possible to evaluate the observed effect or its precision without those results.

The total enrollment is reported as 68, but the number treated, the number meeting the modified Intent-to-Treat definition, and the number with an evaluable response are not reported in the registry record. Missing-data rules, handling of unevaluable assessments, and sensitivity analyses are also not reported. The completeness of endpoint ascertainment therefore cannot be assessed.

Non-randomized allocation and no masking limit the strength of comparisons. The arms are categorized by MET alteration and sample source rather than by randomized treatment assignment. The record does not report how patients were assigned, whether baseline characteristics differed, or whether analyses adjusted for relevant differences. Investigator assessment is specified, but independent or blinded response review is not reported.

The summary describes a question about response relative to other available treatments, but the record does not report a concurrent comparator, a defined external benchmark, or a method for making that comparison. The statistical plan, sample-size justification, multiplicity strategy and interim-analysis status are not reported. Although several secondary outcomes are listed, their results and methods are not reported in the information.

Safety reporting is also limited for interpretation: the listed serious event term percentages have no reported denominator, and the record does not provide event-level attribution or comparative safety data. The study status is completed, but completion alone does not resolve the missing efficacy and analysis details.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Study of MGCD265 in Patients With Non-Small Cell Lung Cancer With Activating Genetic Alterations in MET — NCT02544633.
• Registry record last updated 2020-03-04; status last verified 2020-02.
• Results first posted 2019-09-10.
• 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

This completed Phase 2 study evaluated oral MGCD265 in patients with locally advanced, unresectable or metastatic non-small cell lung cancer and activating MET alterations. Enrollment was 68. The parallel, non-randomized, unmasked arms were defined by mutation or amplification findings in tumor tissue or ctDNA. The summary describes twice-daily administration and previous chemotherapy as a patient requirement.

The primary endpoint was objective response rate, defined as confirmed complete or partial response by investigator assessment under RECIST 1.1, up to 3 months. The analysis population was defined as patients who received at least one dose. The registry record does not report the primary response result, confidence interval, or analysis denominator.

Secondary outcomes included response duration, progression-free survival, survival measures, adverse events and plasma concentration measures. Serious and other adverse event counts and selected serious event terms are reported, but the record does not establish comparative safety or causation. The registry lists 17 outcome measures and 4 analyses; the statistical plan, missing-data handling and multiplicity approach are not reported.