Non Small Cell Lung Cancer
Conditions
Keywords
non small cell lung cancer, NSCLC, EGF816, INC280, tyrosine kinase inhibitor, c-MET
Brief summary
The purpose of this study was to determine the maximum tolerated dose (MTD) / recommended phase 2 dose (RP2D) of nazartinib (EGF816) in combination with capmatinib (INC280) and to estimate the preliminary anti-tumor activity of nazartinib in combination with capmatinib in participants with advanced non-small cell lung cancer (NSCLC) with documented EGFR mutation.
Detailed description
This study was designed as a Phase Ib/II, multi-center, open-label study starting with a Phase Ib dose escalation part followed by a Phase II expansion part. Oral nazartinib (once daily) and capmatinib (twice daily) was administered on a continuous schedule until participant experienced unacceptable toxicity, progressive disease (PD) and/or treatment was discontinued at the discretion of the investigator or withdrawal of consent/opposition to use data/biological samples. Study treatment could be continued beyond Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) defined PD, in the judgment of the investigator, when there was evidence of clinical benefit and the subject wished to continue with the study treatment. In Phase Ib part, participants with NSCLC harboring EGFR activating mutations were enrolled. At the end of the Phase Ib part, once the MTD or RP2D of nazartinib in combination with capmatinib was declared, additional participants with NSCLC were enrolled in the Phase II part in order to assess the preliminary anti-tumor activity of nazartinib in combination with capmatinib. Participants with locally advanced or metastatic NSCLC were assigned into different groups according to their resistance mechanisms. As per the Protocol amendment 7, an additional group (Group 5) was included into study CINC280X2105C, which was intended to support study CINC280L12301. After thorough and careful assessment of study CINC280L12301 enrollment status, projected study completion timelines, and the changing clinical landscape, Novartis made the decision to discontinue the study. Importantly, this decision was not driven by safety concerns; no new safety signals were observed in the study participants or in the ongoing capmatinib program. As such, Group 5 data was no longer needed and the new arm in study CINC280X2105C was not opened as planned.
Interventions
DRUGCapmatinib
In the Phase 1, capmatinib was administered orally, twice per day, at a dose of 200 mg or 400 mg, in fasted state. In the Phase II, participants received capmatinib at the RP2D (400 mg twice per day) in fasted state (Groups 1, 2 and 3) or fed state (Group 4). Participants in Phase II Group 5 were to start with capmatinib monotherapy (fasted or fed state) and then would have had the opportunity to continue with the combination of nazartinib and capmatinib (fasted or fed state).
DRUGNazartinib
In the Phase 1, nazartinib was administered orally, once a day, at a dose of 50 mg, 75 mg, 100 mg or 150 mg in fasted state. In the Phase II, participants received nazartinib at the RP2D (100 mg once daily) in fasted state (Groups 1, 2 and 3) or fed state (Group 4). Participants in Phase II Group 5 were to start with capmatinib monotherapy (fasted or fed state) and then would have had the opportunity to continue with the combination of nazartinib and capmatinib (fasted or fed state).
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion criteria: \- Participants in Phase Ib and Phase II Groups 1 to 4: histologically documented, locally advanced or recurrent (stage IIIB who were not eligible for combined modality treatment) or metastatic (Stage IV) NSCLC. Participants in Phase II Group 5: stage IIIB/IIIC (not amenable to curative surgery, chemoradiation or radiation) or stage IV NSCLC * Participants in Phase Ib and Phase II Groups 1 to 4: locally documented EGFR mutation L858R and/or ex19del, or a characterized de novo EGFR T790M mutation (or other rare activating mutations that confer sensitivity to 1st and 2nd generation EGFR inhibitors (e.g. L861Q, G719X, S768I), or a characterized de novo EGFRT790M mutation. * Presence of at least one measurable lesion according to RECIST v.1.1 * ECOG performance status ≤1 * Participants had to be screened for HBV. Participants who were either HBsAg positive or HBV-DNA positive had to be willing and able to take antiviral therapy 1-2 weeks prior to 1st dose of EGF816 treatment and continue on antiviral therapy for at least 4 weeks after the last dose of EGF816. * Participants had to be screened for HCV. Participants had to have negative hepatitis C antibody (HCV Ab) or were HCV Ab positive but with an undetectable level of HCV-RNA. Note: participants with detectable HCV-RNA were not eligible for the study. * Phase Ib only: documented progression of disease according to RECIST v1.1 while on continuous treatment with EGFR TKI (e.g.: erlotinib, gefitinib or afatinib). * Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI resistant) only: Participants demonstrated a documented clinical benefit (CR (any duration), PR (any duration), or SD for at least 6 months) on prior EGFR TKI (e.g. erlotinib, gefitinib or afatinib, and subsequently demonstrated progression according to RECIST v1.1. * Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI naïve) only: Advanced NSCLC participants who were not previously treated with any therapy known to inhibit EGFR and harbor de novo T790M mutation . * Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic) only: participants had to harbor an EGFR activating mutation and had to be naïve from any line of systemic antineoplastic therapy in the advanced setting. * Phase II Group 4 (EGFRmut, any T790M, any c-MET, 1L (treatment-naïve), 2//3L antineoplastic): All participants had to harbor an EGFR activating mutation and 2/3L participants had to have failed (defined as intolerance to treatment or documented disease progression) a maximum of 2 prior lines of antineoplastic therapy in the advanced setting * Phase II Group 5 only: Histologically or cytologically confirmed diagnosis of NSCLC (excluding squamous cell carcinoma) with all the following: 1. EGFR mutations known to be associated with EGFR TKI sensitivity. This had to be assessed as part of the participant standard of care by a validated test for EGFR mutations, as per local regulations. Exon 19 del, L858R, either alone or in combination with other EGFR sensitivity mutation assessed by a Clinical Laboratory Improvement Amendments (CLIA) certified USA laboratory or an accredited local laboratory outside the USA had to be documented in the participant source documents before the participant consented for pre-screening for MET amplification status. 2. EGFR T790M negative status for participants who had progressed on first or second generation EGFR TKI, or third generation EGFR TKI other than osimertinib, as per tissue-based result from a CLIA-certified USA laboratory or an accredited local laboratory outside of the USA, by a validated test according to local regulations. 3. MET gene amplification defined as: Gene copy number (GCN) ≥ 5 per tissue-based result from a CLIA-certified USA laboratory or an accredited local laboratory outside of the USA by a test that is validated according to local regulations with results documented in the participant source documents. 4. Histological transformation from NSCLC into small cell lung cancer (SCLC) following previous EGFR TKI treatment were excluded. * Participants had to have progressed on one prior line of therapy either to first/second generation EGFR TKIs, osimertinib or other third generation EGFR TKIs for advanced/metastatic disease (stage IIIB/IIIC \[not amenable to curative surgery, chemoradiation or radiation or stage IV NSCLC). * Participants had to have a life expectancy of at least 3 months. Key
Exclusion criteria
* Phase Ib: * More than one previous treatment line with erlotinib, gefitinib or afatinib * Previous treatment with any investigational agent known to inhibit EGFR (mutant or wild-type) * Participants who had received more than three prior lines of antineoplastic therapies (including EGFR TKI) in advanced setting. * Phase II Group 1 (EGFRmut, any T790M, any c-MET, 2/4L antineoplastic, EGFR TKI resistant): * More than 3 prior lines of systemic antineoplastic therapies (including EGFR TKI) in the advanced setting * More than 1 previous treatment line with 1st or 2nd generation EGFR TKI (e.g. erlotinib, gefitinib, afatinib) in the advanced setting * Previous treatment with an investigational or marketed 3rd generation EGFR TKI (e.g. AZD9291, CO-1686, ASP8273, EGF816) * Previous treatment with an investigational or marketed agent known to inhibit EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor). * Phase II Group 2 (EGFRmut, de novo T790M, any c-MET, 1/3L antineoplastic, EGFR TKI naïve): * More than two previous treatment lines of systemic antineoplastic therapies in the advanced setting * Previous treatment with an investigational or marketed agent that inhibits EGFR. EGFR inhibitors include (but not limited to) all generations of EGFR TKI (e.g.erlotinib, gefitinib, afatinib, AZD9291, CO-1686, ASP8273, EGF816) or other anti-EGFR or EGFR monoclonal antibody therapy or dual TKI inhibitors. * Phase II Group 3 (EGFRmut, T790M negative, any c-MET, 1L antineoplastic): * De novo EGFR T790M mutation identified by central assessment * Previous treatment with any systemic antineoplastic therapy in the advanced setting (NSCLC stage IIIB or IV. Participants who received only one cycle of antineoplastic therapy in the advanced setting were allowed). * Phase II Group 4 (EGFRmut, any T790M, any c-MET, 1/3L antineoplastic): * More than 2 prior lines of systemic antineoplastic therapies in the advanced setting * Previous treatment with an investigational or marketed 3rd generation EGFR TKI (e.g. AZD9291, CO-1686, ASP8273, EGF816) * Previous treatment with an investigational or marketed agent known to inhibit EGFR (e.g. EGF monoclonal antibody therapy, dual TKI inhibitor). * Previous treatment with a c-MET inhibitor or HGF-targeting therapy. * Participants with symptomatic brain metastases. * Phase II Group 5: Participants with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms. * Presence or history of another malignancy. Exception: Participants who had been disease-free for 3 years, or participants with a history of adequately treated in-situ carcinoma of the uterine cervix, completely resected basal or squamous cell carcinoma, non-melanomatous cancer of skin, history of stage IA melanoma that had been cured, were eligible. For Phase II Group 5: Presence or history of a malignant disease other than NSCLC that had been diagnosed and/or required therapy within the past 3 years. Exceptions to this exclusion include completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type. * Undergone a bone marrow or solid organ transplant. * Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory). For Group 5: Participants with known history of testing positive for human immunodeficiency virus (HIV) infection, and with a history of Acquired ImmunoDeficiency Syndrome (AIDS) defining opportunistic infections in the last 12 months prior to the first dose of study treatment had to be excluded * Participants receiving concomitant immunosuppressive agents or chronic corticosteroids used at the time of study entry except for control of brain metastases, topical applications, inhaled sprays, eye drops or local injections * Participants with clinically significant, uncontrolled cardiovascular disease * Presence or history of interstitial lung disease or interstitial pneumonitis * Participants who had not recovered from all toxicities related to prior anticancer therapies to grade ≤1 (CTCAE v 4.03) * Participants who had out of range laboratory values * Participants who received live vaccines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) | Up to first 28 days of treatment | Number of participants with DLTs in the Phase Ib part. A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with EGF816 in combination with INC280 during the escalation part of the study (Phase Ib) |
| Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1 | Up to approximately 4 years | ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by investigator's assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). ORR was assessed in Group 1, 2 and 3 (Phase II part). CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Phase II Group 4: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | From start of treatment up to 30 days after last dose of study treatment, assessed up to 3.7 years | Number of participants in Group 4 (Phase II part) with AEs and SAEs. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE. |
| Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | From start of treatment until end of treatment, assessed up to 3.6 years | Number of participants with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 in the Group 4 (Phase II part). |
| Phase II Group 4: Dose Intensity | From start of treatment until end of treatment, assessed up to 3.6 years | Dose intensity, defined as the ratio of total dose received and actual duration, for participants in Group 4 (Phase II part) |
| Phase II Group 5: ORR Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy | Up to approximately 3 years (while on INC280 monotherapy) | ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by Investigator assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for participants in Group 5 (Phase II part) while on treatment with INC280 monotherapy. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | From date of first dose to first documented disease progression or death, assessed up to approximately 5 years | PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Phase Ib participants |
| Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | From date of first dose to first documented disease progression or death, assessed up to approximately 4 years | PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Group 1, 2, 3 and 4 (Phase II) |
| Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | From the date of the first dose to the date of first documented response, up to approximately 5 years | TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Phase Ib participants. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | From the date of the first dose to the date of first documented response, up to approximately 4 years | TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Group 1, 2, 3 and 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | From date of first documented response to first documented disease progression or death, assessed up to approximately 5 years | DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Phase Ib participants CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | From date of first documented response to first documented disease progression or deaths, assessed up to approximately 4 years | DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Group 1, 2, 3 and 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | Up to approximately 5 years | DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease (SD) determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Phase Ib participants CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. |
| Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | Up to approximately 4 years | DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Group 1, 2, 3 and 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. |
| Phase Ib: Overall Survival (OS) | From date of first dose to death, assessed up to approximately 5 years | OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Phase Ib participants |
| Phase II Groups 1, 2, 3 and 4: Overall Survival (OS) | From date of first dose to death, assessed up to approximately 4 years | OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Group 1, 2, 3 and 4 |
| Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. |
| Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. |
| Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment) |
| Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | From start of treatment until end of treatment, assessed up to approximately 5 years | Number of participants in Phase Ib with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 . |
| Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. |
| Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment) |
| Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. |
| Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. |
| Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment) |
| Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. |
| Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. |
| Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment) |
| Phase II Group 5: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy | From date of first documented response to the date of first documented disease progression or death, assessed up to approximately 3 years (while on INC280 monotherapy) | DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Phase II Group 5: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy | Up to approximately 3 years (while on INC280 monotherapy) | DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. |
| Phase II Group 5: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy | Up to approximately 3 years (while on INC280 monotherapy) | PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment. |
| Phase II Group 5: Number of Participants With Dose Modifications for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy | From start of treatment until end of treatment, up to approximately 3 years | Number of participants with dose modifications for INC280 monotherapy as well as INC280 in combination with EGF816 therapy |
| Phase II Group 5: Dose Intensity for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy | From start of treatment until end of treatment, up to approximately 3 years | Dose intensity is defined as the ratio of total dose received and actual duration for INC280 monotherapy as well as INC280 in combination with EGF816 therapy in Group 5 (Phase II) |
| Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days) | Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. |
| Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | From start of treatment until end of treatment, assessed up to approximately 4 years | Number of participants in Groups 1, 2 and 3 (Phase II part) with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 . |
| Phase Ib: Dose Intensity | From start of treatment until end of treatment, assessed up to approximately 5 years | Dose intensity, defined as the ratio of total dose received and actual duration, in Phase Ib participants |
| Phase II Group 1, 2 and 3: Dose Intensity | From start of treatment until end of treatment, assessed up to approximately 4 years | Dose intensity, defined as the ratio of total dose received and actual duration, in Group 1, 2 and 3 (Phase II) |
| Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | Up to approximately 5 years | ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Phase Ib participants. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
| Phase II Group 4: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | Up to approximately 4 years | ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Group 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. |
Countries
Australia, Canada, France, Germany, Italy, Norway, Singapore, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
Participants took part in 19 investigative sites in 11 countries. Due to early study termination, Group 5 (Phase II part) was never opened
Pre-assignment details
The screening period began once patients had signed the study informed consent. All screening/baseline evaluations were performed ≤ 28 days before Cycle 1 Day 1.
Participants by arm
| Arm | Count |
|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD Combination of INC280 200mg twice daily (BID) and EGF816 50mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment | 4 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD Combination of INC280 200mg twice daily (BID) and EGF816 100mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment | 5 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD Combination of INC280 400mg twice daily (BID) and EGF816 75mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment | 3 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD Combination of INC280 400mg twice daily (BID) and EGF816 100mg once daily (QD) in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment | 16 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD Combination of INC280 400mg twice daily (BID) and EGF816 150mg once daily (QD) in fasted state in NSCLC participants with previously documented EGFR mutation, who progressed on EGFR TKI treatment | 5 |
| Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant) NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received 1 to 3 lines of systemic antineoplastic therapy prior to study entry including one line maximum of 1st or 2nd generation EGFR TKI. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state | 52 |
| Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve) NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who received none to 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state | 3 |
| Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic) NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic therapy. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fasted state | 47 |
| Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic) NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who received none to 2 prior lines of systemic antineoplastic therapy prior to study entry. Participants were treated with 400 mg twice daily for INC280 and 100 mg once daily for EGF816 in fed state. | 42 |
| Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant) NSCLC participants with previously documented EGFR activating mutation, T790M negative, acquired MET amplification who have progressed on one prior line of therapy for advanced/metastatic NSCLC disease. Participants started with 400 mg twice daily for INC280 (monotherapy) (fasted or food state) and then had the opportunity to continue with the combination of 400 mg twice daily for INC280 and 100 mg once daily for EGF816 (fasted or food state) | 0 |
| Total | 177 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Post-treatment Follow-up | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Post-treatment Follow-up | Death | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
| Post-treatment Follow-up | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Post-treatment Follow-up | Progressive Disease | 0 | 0 | 0 | 1 | 0 | 9 | 0 | 2 | 3 | 0 |
| Post-treatment Follow-up | Subject/Guardian Decision | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Post-treatment Follow-up | Terminated by Sponsor | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Treatment Phase | Adverse Event | 2 | 0 | 0 | 2 | 1 | 15 | 0 | 5 | 7 | 0 |
| Treatment Phase | Physician Decision | 0 | 0 | 0 | 1 | 0 | 6 | 1 | 2 | 1 | 0 |
| Treatment Phase | Progressive Disease | 2 | 5 | 2 | 11 | 4 | 25 | 2 | 30 | 27 | 0 |
| Treatment Phase | Study Terminated By Sponsor | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 1 | 1 | 0 |
| Treatment Phase | Subject/Guardian Decision | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 4 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant) | Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve) | Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic) | Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic) | Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 65 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants | 2 Participants | 19 Participants | 2 Participants | 17 Participants | 18 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 112 Participants | 5 Participants | 3 Participants | 2 Participants | 11 Participants | 3 Participants | 33 Participants | 1 Participants | 30 Participants | 24 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 98 Participants | 3 Participants | 2 Participants | 1 Participants | 10 Participants | 4 Participants | 26 Participants | 2 Participants | 30 Participants | 20 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 70 Participants | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 22 Participants | 1 Participants | 16 Participants | 21 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 8 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Female | 118 Participants | 3 Participants | 4 Participants | 1 Participants | 9 Participants | 4 Participants | 38 Participants | 2 Participants | 33 Participants | 24 Participants | 0 Participants |
| Sex: Female, Male Male | 59 Participants | 2 Participants | 0 Participants | 2 Participants | 7 Participants | 1 Participants | 14 Participants | 1 Participants | 14 Participants | 18 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 4 / 4 | 0 / 5 | 3 / 3 | 1 / 3 | 2 / 2 | 2 / 16 | 9 / 13 | 0 / 5 | 3 / 5 | 9 / 52 | 26 / 40 | 2 / 3 | 1 / 1 | 5 / 47 | 25 / 37 | 1 / 42 | 22 / 33 |
| other Total, other adverse events | 4 / 4 | 0 / 0 | 5 / 5 | 0 / 0 | 3 / 3 | 0 / 0 | 16 / 16 | 0 / 0 | 5 / 5 | 0 / 0 | 51 / 52 | 0 / 0 | 3 / 3 | 0 / 0 | 47 / 47 | 0 / 0 | 42 / 42 | 0 / 0 |
| serious Total, serious adverse events | 3 / 4 | 0 / 0 | 2 / 5 | 0 / 0 | 3 / 3 | 0 / 0 | 11 / 16 | 0 / 0 | 4 / 5 | 0 / 0 | 29 / 52 | 0 / 0 | 2 / 3 | 0 / 0 | 33 / 47 | 0 / 0 | 26 / 42 | 0 / 0 |
Outcome results
Primary
Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs)
Number of participants with DLTs in the Phase Ib part. A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 28 days of treatment with EGF816 in combination with INC280 during the escalation part of the study (Phase Ib)
Time frame: Up to first 28 days of treatment
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816, and who either completed a minimum exposure requirement or who had a DLT during the first 28 days of treatment (Cycle 1)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs) | 2 Participants |
Primary
Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1
ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by investigator's assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). ORR was assessed in Group 1, 2 and 3 (Phase II part). CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 4 years
Population: All participants in Group 1, 2 or 3 (Phase II part) who received at least one dose of either INC280 or EGF816
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1 | 28.8 Percentage of participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1 | 33.3 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1 | 61.7 Percentage of participants |
Primary
Phase II Group 4: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, for participants in Group 4 (Phase II part)
Time frame: From start of treatment until end of treatment, assessed up to 3.6 years
Population: All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Dose Intensity | INC280 | 666.2 milligram/day | Standard Deviation 148.97 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Dose Intensity | EGF816 | 87.4 milligram/day | Standard Deviation 14.82 |
Primary
Phase II Group 4: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Number of participants in Group 4 (Phase II part) with AEs and SAEs. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment is categorized as SAE.
Time frame: From start of treatment up to 30 days after last dose of study treatment, assessed up to 3.7 years
Population: All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | AEs | 42 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) | SAEs | 26 Participants |
Primary
Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 in the Group 4 (Phase II part).
Time frame: From start of treatment until end of treatment, assessed up to 3.6 years
Population: All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 30 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 31 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 12 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 35 Participants |
Primary
Phase II Group 5: ORR Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) determined by Investigator assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) for participants in Group 5 (Phase II part) while on treatment with INC280 monotherapy. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 3 years (while on INC280 monotherapy)
Population: Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Secondary
Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 1 | 12300 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 4710 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 2 Day 1 | 11300 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 4050 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 15 | 11600 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 3400 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 15 | 11800 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 3360 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 1 | 10500 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 4320 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 2 Day 1 | 11100 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 1770 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 15 | 48800 hours*nanogram/mililiter (hr*ng/mL) | — |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 1 | 38300 hours*nanogram/mililiter (hr*ng/mL) | — |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 15 | 28900 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 12700 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 1 | 22200 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 10700 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 2 Day 1 | 21600 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 7370 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 15 | 23000 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 3440 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 1 | 23000 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 11600 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 2 Day 1 | 24900 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 5190 |
Secondary
Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 1 | 3920 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 1450 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 2 Day 1 | 4080 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 1130 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 15 | 5200 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 2010 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 15 | 9630 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 4060 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 1 | 5850 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 4380 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 2 Day 1 | 7460 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 2340 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 15 | 7330 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 108 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 1 | 4010 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 534 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 15 | 11100 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 5340 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 1 | 5930 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 3600 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 2 Day 1 | 10500 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 7480 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 15 | 16400 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 5670 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 1 | 10500 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 3400 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 2 Day 1 | 11400 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 2360 |
Secondary
Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment
DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease (SD) determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Phase Ib participants CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Time frame: Up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 100 Percentage of participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 60.0 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 33.3 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 62.5 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 80.0 Percentage of participants |
Secondary
Phase Ib: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, in Phase Ib participants
Time frame: From start of treatment until end of treatment, assessed up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Dose Intensity | INC280 | 319.1 milligram/day | Standard Deviation 101.09 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Dose Intensity | EGF816 | 40.0 milligram/day | Standard Deviation 12.6 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Dose Intensity | INC280 | 356.9 milligram/day | Standard Deviation 71.14 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Dose Intensity | EGF816 | 89.6 milligram/day | Standard Deviation 17.93 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Dose Intensity | INC280 | 596.3 milligram/day | Standard Deviation 200.24 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Dose Intensity | EGF816 | 60.0 milligram/day | Standard Deviation 13.36 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Dose Intensity | EGF816 | 85.2 milligram/day | Standard Deviation 17.28 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Dose Intensity | INC280 | 658.2 milligram/day | Standard Deviation 158.18 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Dose Intensity | INC280 | 463.4 milligram/day | Standard Deviation 212.52 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Dose Intensity | EGF816 | 97.7 milligram/day | Standard Deviation 36.43 |
Secondary
Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Phase Ib participants CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: From date of first documented response to first documented disease progression or death, assessed up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816 and had a documented response (CR or PR)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 8.8 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 14.8 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 25.3 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 8.0 Months |
Secondary
Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants in Phase Ib with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 .
Time frame: From start of treatment until end of treatment, assessed up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 2 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 2 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 2 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 2 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 4 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 2 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 2 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 1 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 2 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 2 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 1 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 2 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 10 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 12 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 11 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 5 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 5 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 3 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 5 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 5 Participants |
Secondary
Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment
ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Phase Ib participants. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | 0 Percentage of participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | 40.0 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | 33.3 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | 50.0 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | 60.0 Percentage of participants |
Secondary
Phase Ib: Overall Survival (OS)
OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Phase Ib participants
Time frame: From date of first dose to death, assessed up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Overall Survival (OS) | 10.1 Months |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Overall Survival (OS) | 56.5 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Overall Survival (OS) | 7.0 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Overall Survival (OS) | 17.2 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Overall Survival (OS) | 31.5 Months |
Secondary
Phase Ib: Peak Plasma Concentration (Cmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 1 | 258 nanogram/mililiter (ng/mL) | Standard Deviation 104 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 2 Day 1 | 269 nanogram/mililiter (ng/mL) | Standard Deviation 90.8 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 15 | 361 nanogram/mililiter (ng/mL) | Standard Deviation 165 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 15 | 677 nanogram/mililiter (ng/mL) | Standard Deviation 321 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 1 | 465 nanogram/mililiter (ng/mL) | Standard Deviation 323 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 2 Day 1 | 583 nanogram/mililiter (ng/mL) | Standard Deviation 261 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 15 | 517 nanogram/mililiter (ng/mL) | Standard Deviation 180 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 1 | 302 nanogram/mililiter (ng/mL) | Standard Deviation 8.49 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 15 | 595 nanogram/mililiter (ng/mL) | Standard Deviation 261 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 1 | 381 nanogram/mililiter (ng/mL) | Standard Deviation 231 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 2 Day 1 | 604 nanogram/mililiter (ng/mL) | Standard Deviation 365 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 15 | 1010 nanogram/mililiter (ng/mL) | Standard Deviation 354 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 1 | 777 nanogram/mililiter (ng/mL) | Standard Deviation 281 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 2 Day 1 | 814 nanogram/mililiter (ng/mL) | Standard Deviation 137 |
Secondary
Phase Ib: Peak Plasma Concentration (Cmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 15 | 3070 nanogram/mililiter (ng/mL) | Standard Deviation 1120 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 2 Day 1 | 3590 nanogram/mililiter (ng/mL) | Standard Deviation 1620 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 1 | 3630 nanogram/mililiter (ng/mL) | Standard Deviation 588 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 1 | 2530 nanogram/mililiter (ng/mL) | Standard Deviation 1080 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 2 Day 1 | 2800 nanogram/mililiter (ng/mL) | Standard Deviation 797 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 15 | 2840 nanogram/mililiter (ng/mL) | Standard Deviation 1350 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 1 | 8000 nanogram/mililiter (ng/mL) | — |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 15 | 12000 nanogram/mililiter (ng/mL) | — |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 15 | 5780 nanogram/mililiter (ng/mL) | Standard Deviation 2640 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 1 | 5100 nanogram/mililiter (ng/mL) | Standard Deviation 2550 |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 2 Day 1 | 4830 nanogram/mililiter (ng/mL) | Standard Deviation 1390 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 2 Day 1 | 6370 nanogram/mililiter (ng/mL) | Standard Deviation 1060 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 15 | 4350 nanogram/mililiter (ng/mL) | Standard Deviation 933 |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 1 | 5930 nanogram/mililiter (ng/mL) | Standard Deviation 1330 |
Secondary
Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Phase Ib participants
Time frame: From date of first dose to first documented disease progression or death, assessed up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 5.6 Months |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 7.4 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 3.5 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 5.7 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 14.5 Months |
Secondary
Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 1 | 3.03 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 2 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 15 | 2.07 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 15 | 3.95 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 1 | 3.90 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 2 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 15 | 4.00 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 1 | 3.00 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 15 | 5.90 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 2 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 15 | 3.93 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 2 Day 1 | 3.05 Hours (hr) |
Secondary
Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 1 | 1.07 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 2 Day 1 | 1.00 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 15 | 1.12 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 15 | 2.00 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 1 | 2.00 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 2 Day 1 | 2.00 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 15 | 1.17 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 1 | 2.00 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 15 | 1.97 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 1 | 2.01 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 2 Day 1 | 1.94 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 15 | 1.50 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 1 | 2.00 Hours |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 2 Day 1 | 1.51 Hours |
Secondary
Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment
TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Phase Ib participants. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: From the date of the first dose to the date of first documented response, up to approximately 5 years
Population: All participants in Phase Ib part who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | NA Months |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | NA Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | NA Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | 3.5 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | 4.5 Months |
Secondary
Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment
DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1. DCR was assessed in Group 1, 2, 3 and 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Time frame: Up to approximately 4 years
Population: All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 59.6 Percentage of participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 100 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 93.6 Percentage of participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment | 81.0 Percentage of participants |
Secondary
Phase II Group 1, 2 and 3: Dose Intensity
Dose intensity, defined as the ratio of total dose received and actual duration, in Group 1, 2 and 3 (Phase II)
Time frame: From start of treatment until end of treatment, assessed up to approximately 4 years
Population: All participants in Group 1, 2 and 3 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 and 3: Dose Intensity | INC280 | 662.9 milligram/day | Standard Deviation 160.73 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 and 3: Dose Intensity | EGF816 | 85.2 milligram/day | Standard Deviation 18.21 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 and 3: Dose Intensity | INC280 | 562.9 milligram/day | Standard Deviation 38.36 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 and 3: Dose Intensity | EGF816 | 76.3 milligram/day | Standard Deviation 15.31 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 and 3: Dose Intensity | INC280 | 634.7 milligram/day | Standard Deviation 172.33 |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 and 3: Dose Intensity | EGF816 | 84.8 milligram/day | Standard Deviation 15.53 |
Secondary
Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618
Number of participants in Groups 1, 2 and 3 (Phase II part) with at least one dose reduction of INC280, at least one dose interruption of INC280, at least one dose reduction of EGF816 and at least one dose interruption of EGF816 .
Time frame: From start of treatment until end of treatment, assessed up to approximately 4 years
Population: All participants in Group 1, 2 and 3 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 33 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 31 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 17 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 34 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 3 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 3 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 2 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 3 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of EGF816 | 40 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Interruption of INC280 | 39 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of EGF816 | 23 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618 | Dose Reduction of INC280 | 34 Participants |
Secondary
Phase II Group 4: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment
ORR is defined as percentage of participants with best overall response of PR+CR determined by Investigator's assessment in accordance to RECIST 1.1. ORR was assessed in Group 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: Up to approximately 4 years
Population: All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Group 4: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment | 42.9 Percentage of participants |
Secondary
Phase II Group 5: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
DCR is defined as the percentage of participants with best overall response of CR, PR, or SD determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.
Time frame: Up to approximately 3 years (while on INC280 monotherapy)
Population: Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Secondary
Phase II Group 5: Dose Intensity for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy
Dose intensity is defined as the ratio of total dose received and actual duration for INC280 monotherapy as well as INC280 in combination with EGF816 therapy in Group 5 (Phase II)
Time frame: From start of treatment until end of treatment, up to approximately 3 years
Population: Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Secondary
Phase II Group 5: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: From date of first documented response to the date of first documented disease progression or death, assessed up to approximately 3 years (while on INC280 monotherapy)
Population: Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Secondary
Phase II Group 5: Number of Participants With Dose Modifications for INC280 Monotherapy as Well as INC280 in Combination With EGF816 Therapy
Number of participants with dose modifications for INC280 monotherapy as well as INC280 in combination with EGF816 therapy
Time frame: From start of treatment until end of treatment, up to approximately 3 years
Population: Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Secondary
Phase II Group 5: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression or death due to any cause determined by Investigator assessment in accordance to RECIST 1.1 for participants in Group 5 (Phase II) while on INC280 monotherapy treatment.
Time frame: Up to approximately 3 years (while on INC280 monotherapy)
Population: Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
Secondary
Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment
DOR is defined as the time from first documented response (PR or CR) to the date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1 or death due to underlying cancer. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. DOR was assessed in Group 1, 2, 3 and 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: From date of first documented response to first documented disease progression or deaths, assessed up to approximately 4 years
Population: All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816 and had a documented response (CR or PR)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 6.5 Months |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 12.0 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 11.6 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment | 14.5 Months |
Secondary
Phase II Groups 1, 2, 3 and 4: Overall Survival (OS)
OS is defined as the time from first dose of the study treatment to the date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant was not known to have died, survival was censored at the date of last contact. OS was assessed in Group 1, 2, 3 and 4
Time frame: From date of first dose to death, assessed up to approximately 4 years
Population: All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 1, 2, 3 and 4: Overall Survival (OS) | 18.8 Months |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Overall Survival (OS) | 5.6 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Groups 1, 2, 3 and 4: Overall Survival (OS) | 25.6 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Overall Survival (OS) | 28.9 Months |
Secondary
Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment
PFS is defined as time from date of first dose of study treatment to date of first documented disease progression determined by Investigator assessment in accordance to RECIST 1.1.or death due to any cause. The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, PFS is censored at the date of last adequate tumor assessment. PFS was assessed in Group 1, 2, 3 and 4 (Phase II)
Time frame: From date of first dose to first documented disease progression or death, assessed up to approximately 4 years
Population: All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 5.6 Months |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 3.8 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 10.1 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment | 10.9 Months |
Secondary
Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment
TTR is defined as the time from the date of the first dose to the date of first documented response (CR or PR) determined by Investigator assessment in accordance to RECIST 1.1. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated. If a participant has not had an event, duration was censored at the date of last adequate tumor assessment. TTR was assessed in Group 1, 2, 3 and 4 (Phase II) CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters.
Time frame: From the date of the first dose to the date of first documented response, up to approximately 4 years
Population: All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | NA Months |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | NA Months |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | 1.9 Months |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment | NA Months |
Secondary
Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 1 | 22000 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 8000 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 2 Day 1 | 19700 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 11200 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 1 Day 1 | 16900 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 7360 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280 | Cycle 2 Day 1 | 20500 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 7440 |
Secondary
Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 1 | 6390 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 2460 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 2 Day 1 | 11100 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 2000 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 1 Day 1 | 3420 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 1700 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816 | Cycle 2 Day 1 | 7670 hours*nanogram/mililiter (hr*ng/mL) | Standard Deviation 3330 |
Secondary
Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 1 | 448 nanogram/mililiter (ng/mL) | Standard Deviation 184 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 2 Day 1 | 658 nanogram/mililiter (ng/mL) | Standard Deviation 117 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 1 Day 1 | 239 nanogram/mililiter (ng/mL) | Standard Deviation 107 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of EGF816 | Cycle 2 Day 1 | 447 nanogram/mililiter (ng/mL) | Standard Deviation 175 |
Secondary
Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 1 | 4770 nanogram/mililiter (ng/mL) | Standard Deviation 1460 |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280 | Cycle 2 Day 1 | 4360 nanogram/mililiter (ng/mL) | Standard Deviation 2060 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280 | Cycle 1 Day 1 | 3420 nanogram/mililiter (ng/mL) | Standard Deviation 1550 |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280 | Cycle 2 Day 1 | 3940 nanogram/mililiter (ng/mL) | Standard Deviation 1660 |
Secondary
Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816
Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr and 24 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 2 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 1 Day 1 | 4.00 Hours (hr) |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of EGF816 | Cycle 2 Day 1 | 4.00 Hours (hr) |
Secondary
Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280
Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Actual time of sample collection was used (not the nominal time point as per scheduled assessment)
Time frame: Pre-dose, 0.5 hours (hr) and 1 hr, 2 hr, 4 hr, 8 hr and 12 hr post-dose on Cycle 1 Day 1 and Cycle 2 Day 1 (Cycle=28 days)
Population: All participants in Group 3 and 4 (Phase II part) who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 1 | 1.99 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 2 Day 1 | 1.47 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 1 Day 1 | 2.08 Hours |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280 | Cycle 2 Day 1 | 3.82 Hours |
Post Hoc
All Collected Deaths
On-treatment deaths were collected from first dose of study medication to 30 days after the last dose of study medication. Post-treatment survival follow-up deaths were collected after 30 days post-treatment. All deaths refer to the sum of on-treatment and post-treatment deaths
Time frame: On-treatment: up to approximately 5 years (Phase Ib) and 4 years (Phase II). Post-treatment survival follow-up: Up to approximately 5 years (Phase Ib) and 4 years (Phase II).
Population: All participants in Phase Ib part and Group 1, 2, 3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816. Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | All Collected Deaths | On-treatment deaths | 0 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | All Collected Deaths | All deaths | 4 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 50mg QD | All Collected Deaths | Post-treatment survival follow-up deaths | 4 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | All Collected Deaths | All deaths | 3 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | All Collected Deaths | Post-treatment survival follow-up deaths | 3 Participants |
| Phase IB Part- INC280 200mg BID/ EGF816 100mg QD | All Collected Deaths | On-treatment deaths | 0 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | All Collected Deaths | Post-treatment survival follow-up deaths | 2 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | All Collected Deaths | On-treatment deaths | 1 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 75mg QD | All Collected Deaths | All deaths | 3 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | All Collected Deaths | All deaths | 11 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | All Collected Deaths | On-treatment deaths | 2 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 100mg QD | All Collected Deaths | Post-treatment survival follow-up deaths | 9 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | All Collected Deaths | Post-treatment survival follow-up deaths | 3 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | All Collected Deaths | On-treatment deaths | 0 Participants |
| Phase IB Part- INC280 400mg BID/ EGF816 150mg QD | All Collected Deaths | All deaths | 3 Participants |
| Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant) | All Collected Deaths | Post-treatment survival follow-up deaths | 26 Participants |
| Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant) | All Collected Deaths | On-treatment deaths | 9 Participants |
| Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant) | All Collected Deaths | All deaths | 35 Participants |
| Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve) | All Collected Deaths | All deaths | 3 Participants |
| Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve) | All Collected Deaths | On-treatment deaths | 2 Participants |
| Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve) | All Collected Deaths | Post-treatment survival follow-up deaths | 1 Participants |
| Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic) | All Collected Deaths | Post-treatment survival follow-up deaths | 25 Participants |
| Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic) | All Collected Deaths | All deaths | 30 Participants |
| Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L Antineoplastic) | All Collected Deaths | On-treatment deaths | 5 Participants |
| Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic) | All Collected Deaths | Post-treatment survival follow-up deaths | 22 Participants |
| Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic) | All Collected Deaths | All deaths | 23 Participants |
| Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic) | All Collected Deaths | On-treatment deaths | 1 Participants |