Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Erlotinib Hydrochloride

Gefitinib

Nazartinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Investigational treatment arm of EGF816 (nazartinib).

Investigator's Choice (erlotinib or gefitinib).

EFG816

Investigator's choice between erlotinib or gefitinib. These will be locally sourced.

Erlotinib will be administered orally daily. Gefitinib will be administered orally daily.

erlotinib or gefitinib

Novartis Pharmaceuticals

This is a phase III, open label, randomized controlled multi-center global study designed to evaluate the safety and efficacy of single agent nazartinib (EGF816) compared with investigator's choice (erlotinib or gefitinib) in patients with locally advanced or metastatic NSCLC who are treatment naïve and whose tumors harbor EGFR activating mutations (L858R or ex19del).

blinded independent review committee for primary endpoint of PFS

Phase III Study of Nazartinib (EGF816) Versus Erlotinib/Gefitinib in First-line Locally Advanced / Metastatic NSCLC With EGFR Activating Mutations

A Randomized, Open-label, Phase III Study of Single Agent Nazartinib Versus Investigator's Choice (Erlotinib or Gefitinib) as First-Line Treatment in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring EGFR Activating Mutations

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

PFS using central BIRC assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by BIRC per RECIST 1.1) or death due to any cause, whichever occurs first.

Overall survival is defined as the time from date of randomization to date of death due to any cause.

PFS by Investigator assessment according to RECIST 1.1, is defined as the time from the date of randomization to the date of the first documented progression (as assessed by Investigator per RECIST 1.1) or death due to any cause, whichever occurs first.

PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1 is defined as time from date of randomization to the first documented disease progression (clinical or radiologic) as per investigator assessment on next-line therapy or death from any cause, whichever occurs first.

Time to progression in CNS, defined as time from date of randomization to the date of first documented progression of brain metastases as assessed by central neuro-radiologist BIRC per modified RECIST 1.1 for patients with at least one non-measurable and/or measurable lesion in the brain at baseline.

ORR in accordance with RECIST 1.1. ORR is defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR)

DOR is defined as the time from date of first documented response (CR and PR) to the date of the first documented progression or death due to underlying cancer, whichever occurs first.

DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD).

TTR is defined as the time from the date of randomization to the first documented response CR or PR.

CNS ORR in patients with brain metastases who have measurable disease in the brain at baseline review per modified RECIST 1.1

CNS DoR in patients with brain metastases who have measurable disease in the brain at baseline per modified RECIST 1.1

Peak plasma concentration (Cmax) of EGF816 and its metabolite (LMI258)

Area under the plasma concentration versus time curve (AUC) of EGF816 and its metabolite (LMI258)

Elimination half life (t1/2) of EGF816 and its metabolite (LMI258)

HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life score

HRQoL as measured by European Organization for Research and Treatment of Cancer (EORTC) QLQ-LC13 quality of life score

Global health status/quality of life score of the EQ-5D-5L

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

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

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

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

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

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

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).

Capmatinib

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).

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.

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.

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.

A Phase Ib/II, Multicenter, Open-label Study of EGF816 in Combination With INC280 in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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)

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.

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.

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).

Dose intensity, defined as the ratio of total dose received and actual duration, for participants in Group 4 (Phase II part)

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.

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 .

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 .

Dose intensity, defined as the ratio of total dose received and actual duration, in Phase Ib participants

Dose intensity, defined as the ratio of total dose received and actual duration, in Group 1, 2 and 3 (Phase II)

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.

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.

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

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)

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.

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.

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.

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.

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.

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.

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

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

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods.

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)

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods.

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)

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.

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.

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.

Number of participants with dose modifications 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)

Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events. The total number at risk in the post treatment survival includes patients that entered the post treatment survival follow-up period.

Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)

AEs collected during on-treatment period (up to 30 days post-treatment)

Phase IB Part- INC280 200mg BID/ EGF816 50mg QD (On-treatment)

Deaths collected in the post- treatment survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period

Phase IB Part- INC280 200mg BID/ EGF816 50mg QD (Post-treatment FU)

Phase IB Part- INC280 200mg BID/ EGF816 100mg QD (On-treatment)

Phase IB Part- INC280 200mg BID/ EGF816 100mg QD (Post-treatment FU)

Phase IB Part- INC280 400mg BID/ EGF816 75mg QD (On-treatment)

Phase IB Part- INC280 400mg BID/ EGF816 75mg QD (Post-treatment FU)

Phase IB Part- INC280 400mg BID/ EGF816 100mg QD (On-treatment)

Phase IB Part- INC280 400mg BID/ EGF816 100mg QD (Post-treatment FU)

Phase IB Part- INC280 400mg BID/ EGF816 150mg QD (On-treatment)

Phase IB Part- INC280 400mg BID/ EGF816 150mg QD (Post-treatment FU)

Phase II- EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant (On-treatment)

Phase II- EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant (Post-treatment FU)

Phase II- EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve (On-treatment)

Phase II-EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve (Post-treatment FU)

Phase II- EGFRmut, T790M Negative, Any MET, 1L Antineoplastic (On-treatment)

Phase II- EGFRmut, T790M Negative, Any MET, 1L Antineoplastic (Post-treatment FU)

Phase II-EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic (On-treatment)

Phase II-EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic (Post-treatment FU)

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

Phase IB Part- INC280 200mg BID/ EGF816 50mg 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

Phase IB Part- INC280 200mg BID/ EGF816 100mg 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

Phase IB Part- INC280 400mg BID/ EGF816 75mg 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

Phase IB Part- INC280 400mg BID/ EGF816 100mg 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

Phase IB Part- INC280 400mg BID/ EGF816 150mg QD

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

Phase II- Group 1 (EGFRmut, Any T790M, Any MET, 2/4L Antineoplastic, EGFR TKI Resistant)

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

Phase II- Group 2 (EGFRmut, de Novo T790M, Any MET, 1/3L Antineoplastic, EGFR TKI naïve)

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

Phase II- Group 3 (EGFRmut, T790M Negative, Any MET, 1L 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.

Phase II- Group 4 (EGFRmut, Any T790M, Any MET, 1/3L Antineoplastic)

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)

Phase II- Group 5 (EGFRmut, T790M-, MET GCN≥5, 2L Antineoplastic, EGFR TKI Resistant)

Total

Age, Categorical

Sex: Female, Male

Race/Ethnicity, Customized

No participants were enrolled in Phase II-Group 5 arm due to early study termination.

Study Director

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)

Phase Ib: Number of Participants With Dose Limiting Toxicities (DLTs)

All participants in Group 1, 2 or 3 (Phase II part) who received at least one dose of either INC280 or EGF816

Phase II Group 1, 2 and 3: Overall Response Rate (ORR) by Investigator's Assessment Per RECIST 1.1

SAEs

All participants in Group 4 (Phase II part) who received at least one dose of INC280 or EGF816

Phase II Group 4: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

Dose Reduction of INC280

Dose Interruption of INC280

Dose Reduction of EGF816

Dose Interruption of EGF816

Phase II Group 4: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618

INC280

EGF816

Phase II Group 4: Dose Intensity

Due to early termination of the study, no participants were enrolled in Group 5 (Phase II part)

Phase II Group 5: ORR Per RECIST 1.1 Based on Investigator's Assessment for INC280 Monotherapy

All participants in Phase Ib part who received at least one dose of INC280 or EGF816

Phase Ib: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618

All participants in Group 1, 2 and 3 (Phase II part) who received at least one dose of INC280 or EGF816

Phase II Group 1, 2 and 3: Number of Participants With Dose Reductions and Dose Interruptions of INC280 and EGF618

Phase Ib: Dose Intensity

Phase II Group 1, 2 and 3: Dose Intensity

Phase Ib: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment

Phase II Group 4: Overall Response Rate (ORR) Per RECIST 1.1 Based on Investigator's Assessment

Phase Ib: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment

All participants in Group 1, 2 ,3 and 4 (Phase II part) who received at least one dose of INC280 or EGF816

Phase II Groups 1, 2, 3 and 4: Progression Free Survival (PFS) Per RECIST 1.1 Based on Investigator's Assessment

Phase Ib: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment

Phase II Groups 1, 2, 3 and 4: Time to Response (TTR) Per RECIST 1.1 Based on Investigator's Assessment

All participants in Phase Ib part who received at least one dose of INC280 or EGF816 and had a documented response (CR or PR)

Phase Ib: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment

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)

Phase II Groups 1, 2, 3 and 4: Duration of Response (DOR) Per RECIST 1.1 Based on Investigator's Assessment

Phase Ib: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment

Phase II Group 1, 2 3 and 4: Disease Control Rate (DCR) Per RECIST 1.1 Based on Investigator's Assessment

Phase Ib: Overall Survival (OS)

Phase II Groups 1, 2, 3 and 4: Overall Survival (OS)

Cycle 1 Day 1

Cycle 1 Day 15

Cycle 2 Day 1

All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for INC280.

Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280

Phase Ib: Peak Plasma Concentration (Cmax) of INC280

Phase Ib: Time to Reach Maximum Concentration (Tmax) of INC280

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

Phase II Groups 3 and 4: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 12 Hours (AUC0-12) of INC280

Phase II Groups 3 and 4: Peak Plasma Concentration (Cmax) of INC280

Phase II Groups 3 and 4: Time to Reach Maximum Concentration (Tmax) of INC280

All participants in Phase Ib part who provided at least one evaluable PK concentration and at least one evaluable PK profile for EGF816.

Phase Ib: Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24) of EGF816

Phase Ib: Peak Plasma Concentration (Cmax) of EGF816

Phase Ib: Time to Reach Maximum Concentration (Tmax) of EGF816

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase III Study of Nazartinib (EGF816) Versus Erlotinib/Gefitinib in First-line Locally Advanced / Metastatic NSCLC With EGFR Activating Mutations	NCT03529084	Carcinoma, Non-...	EFG816 erlotinib or ge...	18 Years -	Novartis
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.	NCT02335944	Non Small Cell ...	Capmatinib Nazartinib	18 Years -	Novartis
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.	NCT02335944	Non Small Cell ...	Capmatinib Nazartinib	18 Years -	Novartis
Study to Allow Patients Previously Participating in a Novartis Sponsored Trial to Continue Receiving Capmatinib Treatment as Single Agent or in Combination With Other Treatments or the Combination Treatment Alone	NCT03040973	Advanced Solid ...	Capmatinib Nazartinib Gefitinib Osimertinib	18 Years -	Novartis

Spots Global Cancer Trial Database for nazartinib

Every month we try and update this database with for nazartinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for nazartinib

Every month we try and update this database with for nazartinib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for nazartinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.