A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer (NCT02019693), a na phase 2 study. The primary outcome is Percentage of Participants With Response.

2. Clinical Question

The study was framed as a proof-of-concept evaluation of blocking the HGF/MET pathway in papillary renal cell cancer. The registry background describes MET mutations in some hereditary and sporadic cases and identifies a need for treatment options in advanced disease. These points explain the biological rationale recorded for studying INC280; they do not establish that participants in this trial had a particular MET mutation or that an individual response was caused by MET inhibition.

The main question is descriptive for the enrolled group: how many participants met the registry's response criteria during the stated observation period? A single-group study can characterize outcomes among people who received the investigational drug, but without a concurrent comparator it cannot estimate the difference attributable to treatment relative to another treatment or no treatment. The actual primary response percentage and its uncertainty are not reported in the registry record.

3. Trial Design

This was a phase 2, single-group study of INC280 in papillary renal cell cancer. The National Cancer Institute (NCI) is listed as the sponsor. The registry record lists enrollment of 20, a start date of 2014-01-24, primary completion on 2021-12-17, and status as completed. These dates describe the registry record and do not, by themselves, explain the duration of participation or the timing of any individual outcome assessment.

The intervention description identifies capmatinib (INC280) as a drug administered continuously by mouth at 400 mg twice every day. Masking is listed as none, allocation as NA, and the study model as single group. No separate control group is listed, so the design is not a randomized comparison. The registry explicitly cautions that the arms are not a like-for-like control comparison.

The primary outcome is the percentage of participants with response, assessed under RECIST version 1.1. Its timeframe is from study start until permanent treatment discontinuation, with a stated range of 2 weeks-238 weeks. The secondary outcomes listed are progression-free survival, overall survival, disease control rate, and the number of grades 1-5 adverse events related to treatment. The registry record lists six outcome measures overall, but details for the additional measure are not reported in the registry record.

Design details beyond these entries—including the eligibility criteria, recruitment procedures, planned statistical analysis, and rationale for the enrollment target—are not reported in the registry record. The study's completed status indicates that the record marks it as completed; it does not supply the missing response estimate or analysis details.

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 Percentage of Participants With Response, measured over From start of study until permanent treatment discontinuation (range 2 weeks-238 weeks).

The primary endpoint is the percentage of participants with response. The registry says response was measured using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Under the recorded definitions, complete response means disappearance of all target lesions, while partial response requires at least a 30% decrease in the sum of target-lesion diameters relative to baseline. Progressive disease includes at least a 20% increase relative to the smallest sum on study, or the appearance of one or more new lesions. Stable disease is neither enough shrinkage for partial response nor enough increase for progressive disease, using the smallest on-study sum as the reference.

A response proportion is a compact way to describe how many people in a defined group met the response criteria over the stated follow-up period. It is useful for summarizing tumor response in a study focused on clinical activity. It does not describe how long a response lasted, and it is not interchangeable with progression-free or overall survival. The registry timeframe runs from study start until permanent treatment discontinuation and gives a range of 2 weeks-238 weeks.

The registry record does not report the observed number or percentage of participants with response, nor a confidence interval. Consequently, the endpoint definition is available, but the primary response result and the precision of that result cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A clinical endpoint turns observations into a prespecified summary that can be interpreted consistently. For this study, the primary endpoint is the percentage of participants with response under RECIST version 1.1. The statistical quantity is a proportion: the number meeting the response definition relative to the participants included in the relevant analysis. The registry record does not report that proportion or identify the analysis population used to calculate it.

What does a proportion describe?

A proportion describes the observed frequency of an outcome in a group. It is not a measure of how long the outcome lasted, and it does not automatically identify the effect of an intervention. In a single-group study, the proportion is a description of the enrolled and assessed group. A control group would be needed for a direct comparison with outcomes under a different study condition. No such comparator is listed for this trial.

Because a proportion is estimated from a finite group, its value is subject to sampling uncertainty. A confidence interval is a statistical range intended to communicate that uncertainty under the method's assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. No confidence interval for the primary response outcome is reported in the registry record, so its precision cannot be assessed from the posted results. This general explanation does not supply an estimate for this study.

How should RECIST definitions be read?

The RECIST definitions distinguish changes in target lesions and new lesions. The registry defines complete response as disappearance of all target lesions and partial response as at least a 30% decrease in the sum of target-lesion diameters relative to baseline. Progressive disease is defined by at least a 20% increase relative to the smallest sum on study or the appearance of one or more new lesions. Stable disease occupies the space between the partial-response and progressive-disease thresholds. These categories operationalize radiographic response; they are not, on their own, measures of survival or quality of life.

For an endpoint labeled percentage with response, the response category is the outcome of interest. The registry does not explain additional analysis choices such as whether response required confirmation, how missing scans were classified, or which analysis population was used. Those details are not reported in the registry record and should not be inferred from the RECIST definitions alone.

Why does the design affect the analysis?

A single-group proportion can be summarized without estimating a treatment contrast. In a comparative study, an analysis may estimate a difference between groups, but this study has no like-for-like control arm. Its design therefore cannot support a direct randomized treatment comparison. General statistical methods for comparing groups do not create a comparator that the study did not include.

The registry's sample-size description refers to a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. It explicitly distinguishes this illustration from the trial's own design. These assumptions describe a hypothetical planning calculation, not the method used to analyze the single-group trial and not an observed-power calculation. The trial's original sample-size justification is not reported in the registry record.

What can and cannot be learned from the posted analysis information?

The registry lists zero analyses. It does not report a statistical model, test, confidence interval, p-value, or adjustment procedure for the primary endpoint. Consequently, there is no sponsor-reported inferential result to interpret for response. The record also does not report whether analyses were planned at interim points. Neither a particular model nor an analysis plan should be assumed from the outcome definitions.

In general, model choice depends on the endpoint, design, and data structure. A single-group binary outcome can be described with a proportion and an uncertainty interval, while a time-to-event outcome calls for methods that account for event timing and censoring. These are general methodological distinctions; the registry does not say which methods were used for the listed secondary outcomes.

Over-dispersion is a general concern when observed variability exceeds what a statistical model assumes. If a model assumes less variability than the data contain, uncertainty estimates may be too narrow and inferential conclusions may be overconfident. The registry record does not report a model for which over-dispersion can be assessed, so it is not possible to say whether this issue arose in this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response outcome and secondary outcomes including progression-free survival, overall survival, disease control rate, and treatment-related adverse events. It reports six outcome measures in total. When a study examines multiple outcomes or multiple analyses, the chance of at least one apparently notable result can rise if no adjustment or prioritization is used. This is the general issue of multiplicity; its relevance depends on the analysis plan and the claims being made.

The record identifies the primary endpoint but does not report a multiplicity procedure, a hierarchy among secondary outcomes, or whether any outcomes were exploratory. It also lists zero analyses. Therefore, it is not possible to determine from the registry record how multiplicity was handled or whether the reported outcomes were analyzed according to a prespecified plan. No adjustment should be assumed.

Information about missing outcome data is also not reported in the registry record. The record does not state how many participants had evaluable response assessments, whether anyone discontinued before an assessment, how unavailable scans were treated, or whether missingness was examined by reason. Nor does it specify the analysis population, such as whether the primary endpoint used all enrolled participants or a subset with evaluable assessments.

These omissions matter because outcome denominators and missing-data rules can change the interpretation of a proportion. If participants with unavailable assessments differ from those assessed, a result restricted to assessed participants may not describe the full enrolled group. This is a general methodological concern, not a claim that such a pattern occurred in this trial. Without the analysis population and missing-data handling, the primary result cannot be reconstructed or its robustness evaluated from the registry record.

11. 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: alanine aminotransferase increased (5.0%), atrial fibrillation (5.0%), fever (5.0%), hyponatremia (5.0%), neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, thyroid mass (5.0%).

The registry safety summary lists the Capmatinib (INC280) group with 20 participants at risk for serious adverse events and 6 affected. It lists 20 participants at risk for other adverse events and 20 affected, and records 0 deaths. These are descriptive counts for the study group, not comparative estimates against a control arm.

The serious adverse-event terms listed include alanine aminotransferase increased, atrial fibrillation, fever, hyponatremia, thyroid mass, and pain; each is reported as 5.0%. The registry does not clarify whether people could contribute to more than one term or whether the terms represent events rather than unique participants. The percentages should therefore be read as the record's reported values, not converted into assumed participant counts.

Seriousness and frequency are distinct concepts. A serious adverse event is classified by regulatory seriousness criteria; the registry's summary does not provide full event narratives, duration, grade, timing, or causal assessment for each event. The secondary outcome list separately refers to grades 1-5 adverse events related to treatment, but detailed results for that outcome are not reported in the registry record. These safety entries do not establish comparative risk or causation.

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

The registry record establishes that a phase 2, single-group study of INC280 in papillary renal cell cancer was completed and that its primary endpoint was response under RECIST version 1.1. It also describes continuous oral dosing and reports selected safety counts. However, the primary response percentage is not reported in the registry record. That missing result prevents a numerical assessment of the study's observed response frequency or its precision.

Even if a response proportion were available, a single-group study would not show how outcomes compare with a control group under the same conditions. The observed course of disease can reflect multiple influences, and a single-arm design does not separate those influences from the intervention. The registry's biological rationale is not itself evidence that the drug produced a response in this study.

The serious-adverse-event count and the other safety counts are also descriptive. Without a comparison group and fuller details about event definitions, timing, severity, and attribution, they cannot establish whether the intervention increased or decreased risk. The listed absence of deaths in the safety summary should be interpreted only as the recorded count for this group, not as proof that the intervention carries no risk.

The outcome definitions and design are useful for understanding what the study intended to assess. The missing response estimate, analysis methods, analysis population, and missing-data handling place substantial limits on what can be concluded from the registry record. No claim about treatment effectiveness or lack of effectiveness follows from the information recorded.

13. Why This Trial Matters Statistically

This study illustrates an important distinction between a clinical rationale and an interpretable treatment estimate. A mechanism-based proof-of-concept question can motivate a trial, but the statistical evidence still depends on a reported outcome, its uncertainty, and a design that matches the intended claim. The record describes the MET-inhibition rationale and a RECIST response endpoint, yet does not report the primary response result.

The single-group structure also defines the scope of inference. A response proportion in one treated group can be informative as a description, but it is not a randomized contrast. The registry explicitly notes that arms are not a like-for-like control comparison. This is a reminder that statistical summaries cannot compensate for the absence of a comparator when the question concerns relative outcomes.

Completeness of outcome reporting is central to statistical interpretation. Definitions are not substitutes for results, and counts alone do not reveal precision or address missing assessments. Without the primary estimate, analysis population, and uncertainty measure, readers cannot assess the magnitude of response or how stable the estimate might be.

The safety summary likewise demonstrates why event counts need context. Serious and other adverse events are listed, but causal attribution and detailed analysis are not available in the record. Clear reporting of denominators, event definitions, missingness, and analysis methods enables readers to distinguish what was observed from what can be inferred. In this record, those distinctions set firm limits on conclusions.

14. 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 response result. It also provides no confidence interval or other measure of uncertainty for that endpoint. Although the response criteria and timeframe are described, the outcome's numerical estimate cannot be assessed.

The study is single group, with allocation listed as NA and masking as none. There is no concurrent control group for a like-for-like comparison. The record therefore does not support a direct estimate of treatment effect relative to another intervention or to no study drug. The registry background and biological rationale do not resolve this design limitation.

Enrollment is listed as 20, but the number included in the primary analysis and the number with evaluable response assessments are not reported in the registry record. The handling of missing scans, discontinuations, and other unavailable assessments is also not reported. Because the outcome timeframe ranges from 2 weeks-238 weeks, the extent and timing of observation may differ among participants; details needed to evaluate that variation are absent.

The registry lists six outcome measures and zero analyses, but does not report the analysis methods, multiplicity handling, or analysis populations. It is also not clear from the record how response was operationalized beyond the listed RECIST definitions. Eligibility criteria, the original sample-size justification, and any interim-analysis plan are not reported in the registry record. These gaps restrict both reproducibility and evaluation of selective reporting.

Safety information is limited to summary counts and selected terms. Detailed event-level information, causal assessments, and comparative safety results are not reported in the registry record. These limitations do not imply that unreported analyses or events were absent; they mean that the registry record does not provide the information needed to evaluate them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 2 Study of the MET Kinase Inhibitor INC280 in Papillary Renal Cell Cancer — NCT02019693.
• Registry record last updated 2023-03-21; status last verified 2023-03.
• Results first posted 2023-03-21.
• 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.

18. Record Summary

NCT02019693 is a completed phase 2, single-group study sponsored by the National Cancer Institute (NCI), with enrollment listed as 20. The intervention was capmatinib (INC280), given continuously by mouth at 400 mg twice every day. The primary endpoint was the percentage of participants with response measured using RECIST version 1.1, from study start until permanent treatment discontinuation.

The registry lists secondary outcomes including progression-free survival, overall survival, disease control rate, and treatment-related adverse events. Its safety summary reports serious adverse events in 6 of 20 participants, other adverse events in 20 of 20 participants, and 0 deaths. The primary response result, its uncertainty, analysis methods, analysis population, and missing-data handling are not reported in the registry record. The single-group design does not provide a like-for-like control comparison.