This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment (NCT01610336), a non-randomized phase 2 study. The primary outcome is Phase Ib: Frequency of Dose Limiting Toxicities (DLTs).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01610336 |
| Phase | Phase 2 |
| Condition | Non-small Cell Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 161 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Adults with EGFR-mutated, c-MET-amplified non-small cell lung cancer whose disease had progressed after EGFR inhibitor treatment. The study summary describes patients with c-MET pathway dysregulation who had failed after benefiting from prior gefitinib or erlotinib treatment. The primary safety population was phase Ib patients who received at least a full or partial dose of INC280 or gefitinib.
Intervention
INC280, administered with gefitinib. The phase Ib cohorts used different INC280 doses, schedules, and formulations. The phase II cohorts used INC280 400 mg twice daily as a capsule or tablet, with gefitinib. Arm descriptions identify once-daily and twice-daily schedules.
Comparator
There was no randomized control group. The study was non-randomized, open label, and single group in its overall design, with several dose cohorts. These cohorts describe different regimens and should not be treated as equivalent randomized comparison arms.
Primary question
In phase Ib, how many participants experienced a dose-limiting toxicity while receiving INC280 with gefitinib? A dose-limiting toxicity was defined as an adverse event or abnormal laboratory value judged unrelated to disease progression, inter-current illness, or concomitant medications and meeting criteria defined in the protocol. The registry record gives the endpoint definition but does not report its participant count. The study also assessed safety and efficacy, but specific efficacy results are not reported in the registry record.
3. Trial Design
The registry identifies NCT01610336 as a completed Phase IB/II study sponsored by Novartis Pharmaceuticals. Its stated title describes an open-label, multicenter study of oral INC280 combined with gefitinib in adults with EGFR-mutated, c-MET-amplified non-small cell lung cancer after progression on EGFR inhibitor treatment. The recorded start date is 2012-04-05 and the primary completion date is 2016-06-10. Enrollment was 161.
The design is recorded as non-randomized, unmasked, and single group. The presence of multiple dose cohorts does not make this a randomized comparison: treatment allocation was not random, and the arms are not a like-for-like control comparison. Consequently, differences among cohort summaries cannot by themselves be interpreted as effects caused by dose, schedule, or formulation.
Phase Ib explored INC280 dose levels and formulations in combination with gefitinib. The listed regimens include capsules given once daily or twice daily and tablets given twice daily. Phase II included INC280 400 mg twice daily as either a capsule or tablet. The registry does not report the protocol rationale for selecting these regimens, the process used to move between dose cohorts, or any formal dose-selection rule.
The primary outcome listed is the phase Ib frequency of dose-limiting toxicities, measured as a count of participants, with a timeframe of up to 215 weeks. Secondary outcomes include adverse events, serious adverse events, dose reductions of INC280, dose interruptions of gefitinib, phase II overall survival, progression-free survival and duration of response, and phase I pharmacokinetic parameters. The registry lists 15 outcome measures, but no analyses are listed. Detailed statistical methods, assessment schedules beyond the stated endpoint timeframe, and the relationship between each outcome and the enrolled population 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.
Only the first 6 of 11 groups are shown.
Overall Study
| Stage | INC280 100 mg Cap QD Phase Ib | INC280 200 mg Cap QD Phase Ib | INC280 400 mg Cap QD Phase Ib | INC280 800 mg Cap QD Phase Ib | INC280 200 mg Cap BID Phase Ib | INC280 400 mg Cap BID Phase Ib |
|---|---|---|---|---|---|---|
| STARTED | 5 | 7 | 6 | 7 | 4 | 12 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 5 | 7 | 6 | 7 | 4 | 12 |
Reasons for not completing this period:
| Reason | INC280 100 mg Cap QD Phase Ib | INC280 200 mg Cap QD Phase Ib | INC280 400 mg Cap QD Phase Ib | INC280 800 mg Cap QD Phase Ib | INC280 200 mg Cap BID Phase Ib | INC280 400 mg Cap BID Phase Ib |
|---|---|---|---|---|---|---|
| Progressive Disease | 4 | 6 | 6 | 5 | 3 | 10 |
| Adverse Event | 0 | 0 | 0 | 1 | 1 | 1 |
| Subject/Guardian decision | 1 | 1 | 0 | 1 | 0 | 0 |
| Death | 0 | 0 | 0 | 0 | 0 | 1 |
| Non-Compliance with study treatment | 0 | 0 | 0 | 0 | 0 | 0 |
| Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 |
| Protocol Deviation | 0 | 0 | 0 | 0 | 0 | 0 |
| Transfer to another trial | 0 | 0 | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Set: All patients in phase Ib who received at least one full or partial dose of INC280 or gefitinib.
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.
Only the first 6 of 12 groups are shown.
| Characteristic | Unit | INC280 100 mg Cap QD Phase Ib | INC280 200 mg Cap QD Phase Ib | INC280 400 mg Cap QD Phase Ib | INC280 800 mg Cap QD Phase Ib | INC280 200 mg Cap BID Phase Ib | INC280 400 mg Cap BID Phase Ib |
|---|---|---|---|---|---|---|---|
| Participants analysed | 5 | 7 | 6 | 7 | 4 | 12 | |
| Age, Continuous | years | 57.8 (SD 11.05) | 60.4 (SD 15.27) | 59.5 (SD 6.89) | 51.3 (SD 8.88) | 64.5 (SD 8.89) | 55.9 (SD 10.81) |
| Sex: Female, Male: Female | Participants | 2 | 5 | 4 | 5 | 4 | 4 |
| Sex: Female, Male: Male | Participants | 3 | 2 | 2 | 2 | 0 | 8 |
| Race/Ethnicity, Customized: Russian | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Mixed Ethnicity | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Not reported | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Unknown | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 0 | 0 | 0 | 0 | 0 | 1 |
| Race/Ethnicity, Customized: Southeast Asian | Participants | 1 | 1 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 0 | 0 | 0 | 1 | 2 |
| Race/Ethnicity, Customized: East Asian | Participants | 4 | 6 | 6 | 7 | 3 | 9 |
6. Primary Endpoint
The registry lists the primary outcome as Phase Ib: Frequency of Dose Limiting Toxicities (DLTs), measured over Up to 215 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the phase Ib frequency of dose-limiting toxicities. It is a participant count: the endpoint asks how many people in the specified safety set experienced a qualifying event, rather than measuring the severity of an event on a continuous scale or estimating time until an event. The safety set includes phase Ib patients who received at least a full or partial dose of INC280 or gefitinib.
The registry defines a dose-limiting toxicity as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications and meeting criteria defined in the protocol. This kind of endpoint is used in early-phase dose evaluation to characterize treatment tolerability and identify toxicities relevant to dose decisions. That is a general description of the endpoint’s role; the registry does not report the protocol’s specific qualifying criteria or explain how investigators applied them in individual cases.
The listed timeframe is up to 215 weeks. The registry record does not state the observed number of participants with a dose-limiting toxicity, the denominator for the reported endpoint result, or an estimate of uncertainty such as a confidence interval. Therefore, the endpoint definition can be described, but its result and precision cannot be assessed from the registry record. Other safety counts are recorded separately and should not be substituted for the dose-limiting-toxicity count: adverse events and serious adverse events are not necessarily identical to protocol-defined dose-limiting toxicities.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The study addresses a combination regimen in a selected clinical population: adults with EGFR-mutated, c-MET-amplified non-small cell lung cancer after EGFR inhibitor treatment. It includes dose exploration in phase Ib and phase II cohorts with specified INC280 formulations and schedules. The registry records the intended safety and efficacy outcomes, but the information available does not give a primary endpoint result or efficacy estimates. Thus, the study question and endpoint can be described, while the size and precision of the primary endpoint finding cannot be evaluated from the registry record.
The design limits what can be inferred by comparing cohorts. Treatment allocation was non-randomized, masking was absent, and the overall model is recorded as single group. The arms are explicitly not a like-for-like control comparison. Participants in different cohorts may differ for reasons not captured in the registry record, and treatment choices were not assigned through random allocation. General statistical interpretation: randomization is used to reduce systematic differences between treatment groups; without it, an observed difference between cohorts does not isolate a treatment effect. No causal conclusion about a dose, schedule, or formulation follows solely from cross-cohort contrasts.
The posted safety summaries give counts of participants at risk and counts with serious adverse events, other adverse events, and deaths for the listed dose groups. They offer descriptive information about reported events within those cohorts. They do not establish that an event was caused by INC280 or gefitinib. The registry does not report event-level attribution, adjusted comparisons, or inferential estimates for these counts. Some cohort denominators are small, so descriptive counts should be read with their denominators and not as stable estimates of risk for a wider population. This is a general caution about interpreting event counts, not a claim that any particular count is inaccurate.
The registry lists secondary outcomes including overall survival, progression-free survival, and duration of response in phase II, but does not report their results in the information available. The number of outcome measures is listed as 15, while the number of analyses is listed as 0. This means that analysis details such as effect estimates, confidence intervals, hypothesis tests, and adjusted results are not available in the registry record; it does not establish that no analyses were performed outside the registry.
Sample-size values on the site are planning illustrations calculated from an observed effect under stated assumptions, not the trial’s own design calculations. Such illustrations are not observed power and do not remedy the absence of a randomized comparator. The record does not report the trial’s original sample-size justification or statistical analysis plan. Overall, the available material supports a description of the design and selected safety counts, but not a conclusion about comparative efficacy, a treatment effect, or the precision of the primary endpoint.
9. Statistical Methods Explained
Statistical interpretation starts by matching the method to the design and endpoint. This study is recorded as non-randomized and single group, with no masking. Several arms represent different INC280 doses, schedules, formulations, and study phases, but they do not form randomized control groups. General explanation: random allocation helps make groups comparable on average, including on characteristics that are not measured. When allocation is non-random, differences between groups may reflect underlying differences in who entered each cohort as well as differences in treatment. Comparisons across these arms are therefore descriptive rather than a secure estimate of a causal treatment effect.
What does a participant count represent?
The primary endpoint is a count of participants with dose-limiting toxicity, not a count of all events. A participant who experiences more than one event would still be counted as a participant with the endpoint under a participant-level definition. The registry describes the endpoint unit as participants and defines which kinds of events can qualify, but does not report the observed primary endpoint count. It also does not give enough information to reconstruct the denominator or the event-by-event adjudication. The serious adverse event counts are separate posted safety summaries, not a substitute measure for protocol-defined dose-limiting toxicity.
General statistical explanation: for a binary participant outcome, the basic descriptive quantities are the number experiencing the outcome and the number assessed. An estimated proportion can be accompanied by a confidence interval, which expresses the range of values reasonably compatible with the observed data under the chosen method. With limited numbers of participants, uncertainty can be substantial even when the point estimate appears clear. No primary endpoint estimate or confidence interval is reported in the registry record, so neither a numerical proportion nor its precision should be inferred.
Why does the cohort structure matter?
The study includes phase Ib cohorts across several capsule and tablet regimens and phase II cohorts using INC280 400 mg twice daily as a capsule or tablet. General explanation: sequential or otherwise non-randomized dose cohorts may differ in eligibility, clinical characteristics, timing, or other factors. Even when the treatment combinations are related, cohort-to-cohort contrasts can be confounded. Adjustment for measured characteristics may help in some settings, but it cannot guarantee removal of unmeasured differences. The registry record does not report adjusted analyses, covariate choices, or a plan for comparing these arms. It also explicitly notes that they are not like-for-like control comparisons.
How should uncertainty and event variability be considered?
General explanation: confidence intervals communicate uncertainty around an estimate; a narrow interval generally indicates greater precision than a wide interval, given the method and assumptions. For event counts, the number of participants at risk is important context, because the same count can have different meanings in groups of different sizes. A model may also require attention to over-dispersion, which means that outcomes vary more than a basic model assumes. If over-dispersion is ignored, standard errors can be too small and intervals too narrow. The registry does not report an over-dispersion assessment, a model for the safety counts, or uncertainty estimates. It would therefore be inappropriate to attribute a particular modeling method to this study.
For time-to-event outcomes such as overall survival and progression-free survival, general analysis can account for differing follow-up and censoring, rather than treating every participant as having an observed event or no event at a single fixed point. The registry lists these outcomes for phase II, but does not report estimates, event counts, follow-up summaries, censoring details, or analysis methods. Likewise, duration of response is listed, but its result and analysis details are not reported in the registry record. No time-to-event result should be reconstructed from the outcome names alone.
What do the planning illustrations mean?
The sample-size illustrations use the observed effect and state assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event illustrations, the calculation concerns the total number of events; other illustrations express participants per arm. Rows are framed as planning for a stated fraction of the observed effect. These are planning scenarios, not observed trial outcomes and not the trial’s original design calculations. They are not observed power. The registry does not report the original sample-size justification, and the non-randomized cohorts are not a randomized pair of arms. Consequently, an illustrative sample size based on a contrast should not be interpreted as proof that the study could reliably establish a causal difference between these cohorts.
General explanation: a design calculation depends on assumptions about the effect to detect, outcome variability, significance threshold, allocation, and analysis method. If those assumptions differ from the actual study, the resulting planning number may not describe the study’s operating characteristics. The registry record does not give a formal statistical analysis plan, methods for multiplicity, missing-data procedures, or a stated hierarchy of outcomes. These omissions limit assessment of how the posted outcomes were intended to be analyzed and how any reported findings should be interpreted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 15 outcome measures spanning phase Ib and phase II, including safety outcomes, dose changes, survival outcomes, duration of response, and pharmacokinetic parameters. It lists 0 analyses. A statistical analysis plan, primary and secondary hypothesis hierarchy beyond the named primary endpoint, and any multiplicity adjustment are not reported in the registry record.
General explanation: when many outcomes or multiple comparisons are tested, the chance of at least one apparently notable result can increase. Prespecifying a hierarchy or adjusting interpretation can help address that issue. Without the analysis plan and reported analyses, it is not possible to tell which comparisons were planned, whether exploratory analyses were distinguished from confirmatory ones, or how any multiplicity was handled. The outcome list alone does not show that every outcome was tested or that any particular adjustment was used.
Missing-data methods are also not reported in the registry record. There is no stated approach to missing endpoint assessments, withdrawals, incomplete follow-up, or censoring for the time-to-event outcomes. The primary safety-set definition includes phase Ib patients who received at least a full or partial dose of INC280 or gefitinib, but the registry does not report how many participants met that definition for the primary endpoint or how exclusions and missing observations were handled. The record’s overall enrollment is 161, but that total should not be assumed to be the denominator for every outcome or cohort.
General explanation: the analysis population and missing-data rules matter because they determine who contributes to each estimate. For a safety endpoint, a treated-participant population may be appropriate to describe events among exposed participants, while an efficacy outcome may use a different population or follow-up rule. The registry does not state such outcome-specific rules in the information available. Accordingly, denominator choices, missingness assumptions, and sensitivity analyses cannot be evaluated.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| 100 mg Cap QD (Ph Ib) | 1 | 5 | 20.0% |
| 200 mg Cap QD (Ph Ib) | 2 | 7 | 28.6% |
| 400 mg Cap QD (Ph Ib) | 2 | 6 | 33.3% |
| 800 mg Cap QD (Ph Ib) | 3 | 7 | 42.9% |
| 200 mg Cap BID (Ph Ib) | 0 | 4 | 0.0% |
| 400 mg Cap BID (Ph Ib) | 4 | 12 | 33.3% |
| 600 mg Cap BID (Ph Ib) | 3 | 5 | 60.0% |
| 200 mg Tab BID (Ph Ib) | 5 | 7 | 71.4% |
| 400 mg Tab BID (Ph Ib) | 3 | 8 | 37.5% |
| 400 mg Cap BID (Ph II) | 12 | 53 | 22.6% |
| 400 mg Tab BID (Ph II) | 19 | 47 | 40.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| 100 mg Cap QD (Ph Ib) | 1 of 5 |
| 200 mg Cap QD (Ph Ib) | 0 of 7 |
| 400 mg Cap QD (Ph Ib) | 0 of 6 |
| 800 mg Cap QD (Ph Ib) | 1 of 7 |
| 200 mg Cap BID (Ph Ib) | 0 of 4 |
| 400 mg Cap BID (Ph Ib) | 1 of 12 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| 100 mg Cap QD (Ph Ib) | 5 of 5 |
| 200 mg Cap QD (Ph Ib) | 7 of 7 |
| 400 mg Cap QD (Ph Ib) | 6 of 6 |
| 800 mg Cap QD (Ph Ib) | 7 of 7 |
| 200 mg Cap BID (Ph Ib) | 4 of 4 |
| 400 mg Cap BID (Ph Ib) | 12 of 12 |
Most frequent serious adverse event terms
| Event term | Organ system | 100 mg Cap QD (Ph Ib) | 200 mg Cap QD (Ph Ib) | 400 mg Cap QD (Ph Ib) | 800 mg Cap QD (Ph Ib) | 200 mg Cap BID (Ph Ib) | 400 mg Cap BID (Ph Ib) |
|---|---|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | 0 of 5 | 1 of 7 | 0 of 6 | 0 of 7 | 0 of 4 | 0 of 12 |
| Device related infection | Infections and infestations | 0 of 5 | 0 of 7 | 1 of 6 | 0 of 7 | 0 of 4 | 0 of 12 |
| Pneumonia | Infections and infestations | 0 of 5 | 0 of 7 | 1 of 6 | 0 of 7 | 0 of 4 | 0 of 12 |
| Fibula fracture | Injury, poisoning and procedural complications | 0 of 5 | 0 of 7 | 0 of 6 | 0 of 7 | 0 of 4 | 1 of 12 |
| Blood pressure decreased | Investigations | 0 of 5 | 0 of 7 | 0 of 6 | 1 of 7 | 0 of 4 | 0 of 12 |
| Decreased appetite | Metabolism and nutrition disorders | 0 of 5 | 0 of 7 | 0 of 6 | 0 of 7 | 0 of 4 | 1 of 12 |
| Back pain | Musculoskeletal and connective tissue disorders | 0 of 5 | 1 of 7 | 0 of 6 | 0 of 7 | 0 of 4 | 0 of 12 |
| Peritumoural oedema | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 5 | 0 of 7 | 0 of 6 | 0 of 7 | 0 of 4 | 1 of 12 |
| Dizziness | Nervous system disorders | 0 of 5 | 0 of 7 | 0 of 6 | 1 of 7 | 0 of 4 | 0 of 12 |
| Headache | Nervous system disorders | 0 of 5 | 0 of 7 | 1 of 6 | 0 of 7 | 0 of 4 | 0 of 12 |
Most frequent non-serious adverse event terms
| Event term | Organ system | 100 mg Cap QD (Ph Ib) | 200 mg Cap QD (Ph Ib) | 400 mg Cap QD (Ph Ib) | 800 mg Cap QD (Ph Ib) | 200 mg Cap BID (Ph Ib) | 400 mg Cap BID (Ph Ib) |
|---|---|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 2 of 5 | 2 of 7 | 3 of 6 | 6 of 7 | 2 of 4 | 1 of 12 |
| Vomiting | Gastrointestinal disorders | 2 of 5 | 3 of 7 | 2 of 6 | 7 of 7 | 1 of 4 | 1 of 12 |
| Rash | Skin and subcutaneous tissue disorders | 2 of 5 | 3 of 7 | 0 of 6 | 2 of 7 | 2 of 4 | 4 of 12 |
| Hypoalbuminaemia | Metabolism and nutrition disorders | 0 of 5 | 0 of 7 | 0 of 6 | 2 of 7 | 3 of 4 | 7 of 12 |
| Diarrhoea | Gastrointestinal disorders | 1 of 5 | 1 of 7 | 0 of 6 | 2 of 7 | 3 of 4 | 4 of 12 |
| Paronychia | Infections and infestations | 2 of 5 | 1 of 7 | 2 of 6 | 0 of 7 | 2 of 4 | 4 of 12 |
| Decreased appetite | Metabolism and nutrition disorders | 2 of 5 | 2 of 7 | 1 of 6 | 4 of 7 | 1 of 4 | 1 of 12 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 5 | 0 of 7 | 1 of 6 | 2 of 7 | 1 of 4 | 4 of 12 |
| Oedema peripheral | General disorders | 0 of 5 | 0 of 7 | 2 of 6 | 1 of 7 | 1 of 4 | 4 of 12 |
| Amylase increased | Investigations | 2 of 5 | 1 of 7 | 0 of 6 | 0 of 7 | 1 of 4 | 4 of 12 |
Serious events with the highest arm-level rate: dyspnoea (40.0%), angina pectoris (20.0%), myocardial infarction (20.0%), pneumonia (20.0%), cough (20.0%).
The posted safety summaries give, for each listed dose group, the number of participants at risk and the number with serious adverse events, other adverse events, and deaths. These are descriptive counts within each cohort. The serious-event terms listed include dyspnoea, angina pectoris, myocardial infarction, pneumonia, cough, and device related infection, with percentages attached to those terms. The denominator used for those term percentages is not reported in the registry record, so they should not be read as percentages of all enrolled participants without further information.
Counts require their cohort denominators for context. The groups differ in size, phase, formulation, and dosing schedule, so raw counts across groups are not directly comparable. The registry also states that allocation was non-randomized and that the arms are not like-for-like control comparisons. The counts therefore do not estimate a randomized between-treatment contrast.
A serious adverse event is not necessarily a dose-limiting toxicity, and neither category by itself establishes that the study treatment caused the event. The registry does not report attribution details, severity grading beyond the serious-event classification, or inferential comparisons for these counts. Death counts are listed, but their causes and relationship to study treatment are not reported in the registry record. These summaries describe events recorded in the cohorts; they do not establish treatment benefit or harm relative to a control.
12. What the Result Does, and Does Not, Mean
The record identifies a study of INC280 combined with gefitinib in adults with EGFR-mutated, c-MET-amplified non-small cell lung cancer after EGFR inhibitor treatment. It describes a phase Ib dose-exploration component and phase II cohorts, and it specifies a phase Ib dose-limiting-toxicity endpoint. It also records safety counts for serious adverse events, other adverse events, and deaths. Those details support a description of what the study examined and of selected events recorded in its cohorts.
The registry record does not report the observed result for the primary dose-limiting-toxicity endpoint. It lists phase II overall survival, progression-free survival, and duration of response as secondary outcomes, but their results are not reported in the information available. Without those outcome estimates, the registry material does not establish the magnitude or precision of an efficacy finding. A listed outcome is not itself evidence of a favorable, unfavorable, or null result.
The non-randomized design and absence of a like-for-like control arm also limit causal interpretation. Differences between dose or formulation cohorts could reflect differences in the participants or circumstances of the cohorts, not just treatment. The posted adverse-event counts are descriptive and do not establish that treatment caused a reported event. No result should be framed as evidence that the combination works or does not work.
General explanation: a study’s result is most informative when the estimate, uncertainty, population, endpoint definition, and analysis method can all be assessed together. A count without a reported denominator or confidence interval gives less information about precision; an outcome name without a result gives no estimate at all. Here, the primary endpoint definition and some safety counts are available, while the primary endpoint result, efficacy estimates, analysis details, and missing-data procedures are not reported in the registry record.
Sample-size illustrations are planning scenarios based on an observed effect and stated assumptions, not observed power and not evidence that a particular contrast is causal. They should not be used to fill gaps in the registry’s outcome reporting. The appropriate interpretation is limited: this record describes a non-randomized combination study and selected safety observations, but does not report enough outcome and analysis information to determine the size, precision, or comparative meaning of the primary or efficacy results.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way dose exploration, multiple regimens, and outcome reporting intersect. The registry describes several INC280 formulations and schedules alongside gefitinib, with phase Ib and phase II cohorts. Those regimens may be useful to describe as distinct treatment groups, but the non-randomized allocation means their results do not have the protection against group differences that randomization is intended to provide. That design feature is central to interpreting any apparent differences between cohorts.
The primary endpoint is a protocol-defined safety count rather than a comparative efficacy endpoint. Its definition makes clear that not every adverse event qualifies: the event must meet protocol criteria and be assessed as unrelated to disease progression, inter-current illness, or concomitant medications. This highlights the distinction between broad adverse-event summaries and an endpoint designed for dose evaluation. The registry lists the endpoint but does not report its result, so the distinction can be explained without concluding how many participants met the definition.
The record also illustrates why outcome registration and outcome reporting are different. It names several safety, survival, response, and pharmacokinetic outcomes, but lists no analyses. The absence of analysis details prevents review of the statistical methods, precision estimates, missing-data handling, and multiplicity strategy. Those omissions matter because results depend not only on what was measured, but also on who was analyzed and how comparisons were constructed.
Finally, the sample-size illustrations use an observed effect and assumptions for planning, yet the cohorts are not randomized control groups. General statistical lesson: a planning calculation can describe the sample size associated with an assumed target contrast, but it cannot transform a non-randomized comparison into a causal one. For this study, clear separation of descriptive safety counts, planning illustrations, and treatment-effect claims is especially important.
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 registry record gives the study’s overall enrollment and a collection of dose cohorts, but does not report the number of participants contributing to every outcome or the primary endpoint denominator. Enrollment of 161 should not be treated as the analysis population for each endpoint. The primary outcome’s timeframe is listed as up to 215 weeks, but the record does not provide an observed dose-limiting-toxicity count, follow-up distribution, or confidence interval.
The design is non-randomized, unmasked, and single group, and the registry explicitly warns that the arms are not a like-for-like control comparison. This is a specific limitation for interpreting differences among dose and formulation cohorts. The record does not describe whether cohorts were enrolled sequentially, how treatment assignment was made, or whether analyses adjusted for differences among participants. Those details are not reported in the registry record and should not be assumed.
The safety summaries report cohort-level counts, but do not provide attribution details for adverse events or deaths. The denominator underlying the percentages attached to serious-event terms is not stated. The record does not give the primary endpoint result, detailed efficacy results, analysis methods, missing-data procedures, or multiplicity handling. It also does not report the protocol’s specific dose-limiting-toxicity criteria, beyond stating that criteria were defined in the protocol.
Although sample-size illustrations are available, they are planning calculations based on the observed effect and stated assumptions, not the trial’s own sample-size justification. The registry does not report that original justification or the statistical analysis plan. Together, these omissions restrict assessment of precision, robustness, and comparative interpretation. They do not establish that analyses or additional information do not exist outside the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Safety and Efficacy Study of INC280 and Gefitinib in Patients With EGFR Mutated, c-MET-amplified NSCLC Who Have Progressed After EGFRi Treatment — NCT01610336.
- Registry record last updated 2021-04-08; status last verified 2021-03.
- Results first posted 2021-04-08.
- 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.
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18. Record Summary
NCT01610336 is a completed, open-label, non-randomized Phase IB/II study sponsored by Novartis Pharmaceuticals. It evaluated oral INC280 in combination with gefitinib in adults with EGFR-mutated, c-MET-amplified non-small cell lung cancer after EGFR inhibitor treatment. The registry records enrollment of 161 and lists a phase Ib primary endpoint of dose-limiting-toxicity participant count, with a timeframe of up to 215 weeks.
Multiple INC280 doses, schedules, and formulations are described, including phase II regimens of 400 mg twice daily as a capsule or tablet. Secondary outcomes include safety, dose changes, survival, response duration, and pharmacokinetic measures. The registry lists 15 outcome measures and 0 analyses. It reports selected cohort safety counts, but does not report the primary endpoint result, efficacy estimates, analysis methods, or missing-data procedures. Because allocation was non-randomized, the dose groups are not like-for-like control arms, and descriptive differences should not be interpreted as causal treatment effects.