Study of Safety and Efficacy of EGFR-TKI EGF816 in Combination With cMET Inhibitor INC280 in Adult Patients With EGFR Mutated Non Small Cell Lung Cancer.

Phase 1

Terminated

Conditions: Non Small Cell Lung Cancer

Interventions: Drug: Capmatinib
Drug: Nazartinib

Registration Number: NCT02335944

Lead Sponsor: Novartis Pharmaceuticals

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 177

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Phase IB part- NSCLC with EGFR activating mutations	Capmatinib	NSCLC participants who have previously documented EGFR mutation and progressed on EGFR TKI treatment. Participants were treated at a starting dose of 50 mg once a day for EGF816 and 200 mg twice a day for INC280 in fasted state
Phase II- Group 1 (EGFRmut, any T790M, any MET, 2/4L antineoplastic, EGFR TKI resistant)	Capmatinib	NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received one to three lines of systemic antineoplastic therapy prior to study entry including one line maximum of first or second generation EGFR TKI and who progressed on this EGFR TKI treatment line. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Phase II- Group 2 (EGFRmut, de novo T790M, any MET, 1/3L antineoplastic, EGFR TKI naïve)	Capmatinib	NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who are treatment naïve or received maximum 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Phase II- Group 3 (EGFRmut, T790M negative, any MET, 1L antineoplastic)	Capmatinib	NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic systemic therapy prior to study entry. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Phase II- Group 4 (EGFRmut, any T790M, any MET, 1L (treatment naïve) 2-3L antineoplastic)	Capmatinib	NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who were treatment naïve or failed maximum 2 prior lines of any systemic antineoplastic therapy for advanced disease. Participants were treated at the RP2D of INC280 and EGF816 in fed state
Phase II- Group 3 (EGFRmut, T790M negative, any MET, 1L antineoplastic)	Nazartinib	NSCLC participants with previously documented EGFR activating mutation, T790M negative, and any MET status who never received any prior line of systemic antineoplastic systemic therapy prior to study entry. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L, EGFR TKI resistant)	Capmatinib	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 were to start with INC280 monotherapy (twice a day) and would have had the opportunity to continue to combination of EGF816 (once a day) and INC280 (twice a day) based on radiological disease progression evaluation by investigator's assessment per RECIST 1.1
Phase IB part- NSCLC with EGFR activating mutations	Nazartinib	NSCLC participants who have previously documented EGFR mutation and progressed on EGFR TKI treatment. Participants were treated at a starting dose of 50 mg once a day for EGF816 and 200 mg twice a day for INC280 in fasted state
Phase II- Group 1 (EGFRmut, any T790M, any MET, 2/4L antineoplastic, EGFR TKI resistant)	Nazartinib	NSCLC participants with previously documented activating EGFR mutation, with any T790M and MET dysregulation status, who received one to three lines of systemic antineoplastic therapy prior to study entry including one line maximum of first or second generation EGFR TKI and who progressed on this EGFR TKI treatment line. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Phase II- Group 2 (EGFRmut, de novo T790M, any MET, 1/3L antineoplastic, EGFR TKI naïve)	Nazartinib	NSCLC participants harboring T790M mutation in de novo setting, irrespective of the activating mutation status who are treatment naïve or received maximum 2 lines of systemic antineoplastic therapy prior to study entry, but no therapy known to inhibit EGFR. Participants were treated at the RP2D of INC280 and EGF816 in fasted state
Phase II- Group 4 (EGFRmut, any T790M, any MET, 1L (treatment naïve) 2-3L antineoplastic)	Nazartinib	NSCLC participants with previously documented EGFR activating mutations and any T790M and MET status who were treatment naïve or failed maximum 2 prior lines of any systemic antineoplastic therapy for advanced disease. Participants were treated at the RP2D of INC280 and EGF816 in fed state
Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L, EGFR TKI resistant)	Nazartinib	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 were to start with INC280 monotherapy (twice a day) and would have had the opportunity to continue to combination of EGF816 (once a day) and INC280 (twice a day) based on radiological disease progression evaluation by investigator's assessment per RECIST 1.1

Primary Outcome Measures

Name	Time	Method
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.
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)

Secondary Outcome Measures

Name	Time	Method
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 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 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 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: 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 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.
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 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: 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 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 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 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 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 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 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: 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 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.

Trial Locations

Locations (2): Novartis Investigative Site
🇨🇳
Taipei, Taiwan ROC, Taiwan
Massachusetts General Hospital Mass General
🇺🇸
Boston, Massachusetts, United States