A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor (NCT02750215), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The primary outcome is objective response rate (ORR), defined as the percentage with a complete response or partial response. The registry describes complete response as disappearance of all target lesions and partial response as a decrease of at least 30% in the sum of the longest diameters of target lesions. The listed timeframe is through study completion, an average of 14 months.

This question concerns response observed among participants in this particular single-group study. Without a separate comparator, the design cannot by itself distinguish the treatment-associated response pattern from changes that might occur under another treatment or without capmatinib. The registry record lists enrollment of 20, but does not report the primary outcome result, the number included in its analysis, or the statistical uncertainty around an estimate. It therefore describes the study question and design, but does not establish an estimate of ORR from the posted outcome information.

3. Trial Design

The registry describes a phase 2, single-group study of capmatinib (INC280) in NSCLC patients with MET exon 14 alterations who had received a prior MET inhibitor. The study is listed as completed, with enrollment of 20. The condition recorded is malignant non-small cell neoplasm of lung stage IV. Massachusetts General Hospital is listed as the sponsor.

Participants who fulfilled eligibility criteria were to receive capmatinib after screening. The treatment description specifies oral dosing twice daily in 21-day cycles. The record lists no allocation between treatment groups and describes masking as none. There is no separate concurrent control arm listed, so the study is not a randomized comparison and cannot be read as a direct comparison of capmatinib with another intervention.

The registry lists a start of 2016-05 and primary completion of 2021-05. The primary outcome is objective response rate, assessed according to RECIST 1.1 through study completion, an average of 14 months. Secondary outcomes listed include progression-free survival, disease control rate, intracranial response rate, duration of response, overall survival, and treatment-related adverse events by grade. The registry lists seven outcome measures, but does not list outcome analyses.

Some design details needed to interpret the results are not reported in the registry record. These include the eligibility criteria in full, how response assessments were scheduled and reviewed, whether review was independent, and how the analysis population was defined. No statistical analysis plan or sample-size justification is reported in the registry record. The planned treatment description is not evidence that every enrolled participant received the same exposure or completed treatment; those details 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

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, measured over through study completion, an average of 14 months.

Objective response rate measures the percentage of participants whose tumors meet the registry’s criteria for complete or partial response. Under the stated RECIST 1.1 definition, complete response means disappearance of all target lesions. Partial response requires a decrease of at least 30% in the sum of the longest diameters of target lesions. ORR combines those two response categories.

Response rate is used to describe the proportion of a study group that reaches a prespecified tumor-response category during a defined observation period. It is a binary-outcome summary at the participant level: each participant is classified according to whether a complete or partial response was recorded, and the percentage expresses the group frequency. It does not, by itself, describe how long a response lasts, whether disease remained controlled without meeting response criteria, or how participants fare over time. The registry lists duration of response and disease control rate separately as secondary outcomes.

The primary outcome timeframe is through study completion, an average of 14 months. That wording identifies the stated observation window, but does not give each participant’s actual follow-up duration or explain the assessment schedule. The primary response estimate and its uncertainty are not reported in the registry record. Consequently, the endpoint’s definition is available, but its observed value cannot be interpreted from the posted primary outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies objective response rate as a percentage of participants and defines it as the combined proportion with complete or partial response. This is a binary-outcome analysis in general: a participant is classified as having met the response definition or not, and the group result is expressed as a proportion or percentage. The registry does not report the observed response count or percentage, so no numerical estimate can be interpreted.

What would a response estimate describe?

In general, a response proportion summarizes the frequency of a defined event in a specified analysis group over a specified observation period. Here, the event definition is based on RECIST 1.1, and the timeframe is through study completion, an average of 14 months. The registry record does not state the response assessment schedule, whether assessments were reviewed by investigators or independently, or the rules used to classify participants with missing or unevaluable assessments. Those choices can affect how a response proportion is constructed.

A percentage alone would not communicate precision. In general, a confidence interval gives a range of values compatible with the observed data under the method’s assumptions; wider intervals indicate less precision. For a binary outcome, uncertainty depends in part on the number of participants included and the number meeting the outcome definition. No confidence interval or primary response analysis is reported in the registry record, and the analysis denominator is not stated. It is therefore not possible to assess the precision of an ORR estimate from the posted primary outcome information.

Why does the single-group structure matter?

In general, a single-group study can describe outcomes among its participants, but it cannot estimate a randomized contrast with a concurrent control group. Without such a comparator, changes in disease status cannot be separated from other explanations through a between-group comparison. The record lists allocation as not applicable and masking as none, and the study model as single group. The primary endpoint is therefore best understood as a proposed descriptive response measure, rather than evidence from a randomized treatment comparison.

Open-label conduct can matter for outcomes that depend on assessment or classification. The registry’s definition refers to lesion measurements under RECIST 1.1, but it does not report who performed or reviewed those measurements, or whether any independent review was used. This is an unreported methods detail, not evidence that the response assessments were biased. It limits the ability to assess how assessment procedures might have influenced classification.

What can safety counts tell a reader?

General safety summaries count participants or events meeting specified adverse-event definitions. The registry safety data list 20 participants at risk, 2 affected by serious adverse events, and 18 affected by other adverse events in the capmatinib group. These are participant counts, not a comparative risk estimate. The record also lists 15 deaths, but does not report enough detail in this entry to attribute them to treatment or to interpret their timing and causes. A participant may experience more than one event; the registry record does not state whether the listed event categories overlap.

Seriousness and severity are distinct concepts in general safety reporting. Serious adverse events are classified by their consequences or criteria, while grade describes severity. The registry lists treatment-related adverse events by grade as a secondary outcome, but the posted safety figures do not provide a grade distribution. The serious-event terms and percentages should not be mistaken for a complete account of all event types, durations, or grades.

What statistical plan is available?

The registry record lists no outcome analyses. It does not report a statistical analysis plan, the method used to calculate a confidence interval, a hypothesis test, a missing-data approach, or a definition of the primary analysis population. No sample-size justification is reported in the registry record. These omissions mean that readers cannot verify whether the planned analysis matched the endpoint definition or determine how the analysis addressed incomplete follow-up.

In general, prespecified methods help distinguish planned analyses from decisions made after observing outcomes. The registry record names a primary outcome and several secondary outcomes, but does not describe how multiple outcomes or analyses were handled. It is not possible to infer an adjustment strategy, interim analysis, or other analytic procedure from the outcome list alone. The absence of a listed analysis should not be read as evidence that no analysis was conducted outside the registry; it means that an analysis is not reported in the registry record.

The registry also includes a planning-illustration framework based on an observed effect and assumptions such as equal allocation. Those assumptions are not a description of this study’s single-group design, which has no two-arm randomized allocation. Planning sample sizes are not observed study outcomes or observed power. Since the primary response result and its analysis are not reported, no sample-size illustration can supply the missing observed response estimate or its uncertainty.

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("Capmatinib (INC280)")
n      <- c(20)
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  Capmatinib (INC280)  20  2  10.0  1.2  31.7  2.8  30.1  3.0  30.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists objective response rate as the primary outcome and names several secondary outcomes: progression-free survival, disease control rate, intracranial response rate, duration of response, overall survival, and treatment-related adverse events by grade. It does not report how the study handled the possibility of interpreting multiple outcomes. Any prespecified hierarchy, testing sequence, or adjustment for multiple statistical tests is not reported in the registry record. No statistical analysis plan or outcome analyses are listed.

In general, when multiple outcomes or repeated statistical tests are examined, the chance of at least one apparently unusual result can increase. A prespecified strategy can help define which findings are confirmatory and which are exploratory. The registry’s outcome list alone does not establish such a strategy, and it does not justify assuming either that an adjustment was used or that results were treated as independent confirmatory tests.

Missing-data procedures are also not reported in the registry record. The record does not state how participants with no response assessment, incomplete follow-up, or unevaluable scans were handled in the ORR denominator. Nor does it identify an analysis population, such as all enrolled participants or only those with evaluable response assessments. Enrollment of 20 does not establish that all 20 contributed to every outcome analysis.

The registry lists an average timeframe of 14 months for the primary outcome, but does not describe participant-level follow-up or censoring rules. Those details can be particularly important for time-to-event secondary outcomes. The registry record does not report how deaths, withdrawals, treatment discontinuation, or missing assessments were incorporated into those analyses. These gaps limit assessment of attrition, outcome completeness, and the potential effect of analysis choices on the reported estimates.

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: hip fracture (5.0%), edema limbs (5.0%), wound infection (5.0%), seizure (5.0%), stroke (5.0%).

The registry safety entry lists 20 participants at risk in the capmatinib group. It records 2 participants affected by serious adverse events and 18 affected by other adverse events. These are separate registry categories; the entry does not explain whether an individual could be included in both. The record also lists 15 deaths. These counts are descriptive and do not, on their own, establish that capmatinib caused an event or death.

The listed serious adverse-event terms are hip fracture, edema limbs, wound infection, seizure, stroke, and thromboembolic event. Each is shown with a frequency of 5.0%. The record does not supply event-level narratives, timing, duration, severity grades, or information about overlap among those terms. These terms should therefore be read as selected registry-listed serious events, not as a complete account of the safety experience.

The registry names treatment-related adverse events by grade as a secondary outcome, but it does not report a grade breakdown in the posted results. Seriousness and grade are not interchangeable: seriousness describes regulatory criteria, while grade generally describes severity. The available figures should not be used to infer the overall tolerability profile or treatment causality. Further safety-analysis details are not reported in the registry record.

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

The registry record establishes that this was a phase 2, single-group study of capmatinib in people with NSCLC and MET exon 14 alterations who had previously received a MET inhibitor. It defines objective response rate as the primary outcome and gives a RECIST 1.1-based definition of complete and partial response. It also lists secondary outcomes and selected adverse-event counts.

It does not report the primary response percentage, the number of participants who responded, or an uncertainty interval. Without those elements, the posted record cannot quantify the observed response pattern or its precision. The listed enrollment of 20 is not a substitute for an outcome denominator, and it does not show how many participants had evaluable assessments.

The single-group design also means that the study does not provide a randomized comparison with a control group. Even a reported response rate would describe outcomes among study participants rather than establish a comparative treatment effect. The record does not provide evidence from which to separate treatment effects from other potential influences on response.

The safety counts likewise require restrained interpretation. The listed counts and serious-event terms describe what the registry records, but do not establish causation. The listed deaths are not accompanied in this entry by details sufficient to explain their timing or attribution. Absence of those details in the registry record is not evidence that events did or did not occur beyond the reported categories.

Accordingly, the available information supports a description of the study design, endpoint definitions, timeframe, and selected safety data. It does not support a numerical conclusion about the primary endpoint, a treatment comparison, or a complete assessment of benefits and harms. Those conclusions would require outcome analyses and methods not reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry carefully defines objective response rate using complete and partial response categories, but does not report an observed ORR analysis. A reader can understand what the study intended to measure without being able to estimate how often the endpoint occurred or how precise such an estimate would be.

The single-group structure is also central to statistical interpretation. A response proportion in one group can describe the enrolled population, but it does not create a concurrent comparison. Statistical methods cannot remove the design limitation that there is no separately assigned control group in the registry record. This distinction is especially important when outcomes are discussed as treatment effects rather than as descriptive observations.

Enrollment and analysis denominators should not be conflated. The record lists enrollment of 20, but gives no primary outcome analysis population or response denominator. Without these, a percentage cannot be checked against the number assessed, and the influence of missing outcome information cannot be evaluated. The timeframe of through study completion, an average of 14 months, also does not reveal each participant’s follow-up.

Finally, the record shows the value of transparent statistical reporting. An analysis plan, primary estimate, uncertainty interval, and clear missing-data rules would allow readers to judge the numerical evidence and its limits. Their absence does not establish that analyses were never performed; it means that the registry record does not report them. For biostatisticians and clinical researchers, the distinction between what a protocol measures and what the posted results document is essential to calibrated 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.

Several limitations specific to this study record constrain interpretation. The most consequential is that objective response rate, the primary outcome, has a definition and timeframe but no reported result or analysis. The registry record does not report the number of complete or partial responses, the percentage responding, or a confidence interval. It also does not identify the analysis population or denominator.

The study is single group, with allocation not applicable and no separate control arm listed. It therefore cannot provide a randomized comparison with another treatment or control. Masking is listed as none, while details about response-assessment procedures, assessor roles, or independent review are not reported in the registry record.

The registry lists enrollment of 20, but does not report how many participants started treatment, completed treatment, had evaluable scans, or remained under observation through the primary outcome timeframe. The stated average follow-up timeframe does not describe participant-level follow-up or missing assessments. Eligibility criteria beyond the general population description, dose modifications, adherence, and reasons for treatment discontinuation are not reported in the registry record.

Although secondary outcomes are listed, their analyses and estimates are not reported. The statistical analysis plan, missing-data methods, handling of multiple outcomes, and sample-size justification are not reported in the registry record. Safety information is limited to selected counts and terms; event timing, causes, grades, overlap, and details of the listed deaths are not given. These limitations do not establish that the underlying data or analyses do not exist, but they restrict what can be concluded from the registry entry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor — NCT02750215.
• Registry record last updated 2022-03-14; status last verified 2022-03.
• Results first posted 2022-03-14.
• 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

NCT02750215 is a completed phase 2, single-group study sponsored by Massachusetts General Hospital. It enrolled 20 participants and evaluated capmatinib (INC280) in people with advanced NSCLC and MET exon 14 alterations who had received a prior MET inhibitor. The treatment description specifies oral dosing twice daily in 21-day cycles.

The primary outcome is objective response rate by RECIST 1.1 through study completion, an average of 14 months. The registry lists progression-free survival, disease control rate, intracranial response rate, duration of response, overall survival, and treatment-related adverse events by grade as secondary outcomes. It does not report outcome analyses or the primary response result.

The safety entry lists 2 participants with serious adverse events, 18 with other adverse events, and 15 deaths among 20 at risk. These figures are descriptive and do not establish causality. Analysis populations, statistical methods, and further outcome details are not reported in the registry record.