Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Nazartinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W

Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W

Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W

EGF816 150 mg once daily (QD) administered orally as a capsule

EGF816

INC280 400 mg twice daily (BID) administered orally as a tablet

INC280

Nivolumab 3 mg/kg every 2 weeks (Q2W) administered by intravenous infusion

Novartis Pharmaceuticals

To determine the efficacy and safety of nivolumab in combination with EGF816 and of nivolumab in combination with INC280 in previously treated NSCLC patients

This was a phase II, multi-center, open-label study in patients with advanced non-small cell lung cancer (NSCLC). Patients were allocated based on their epidermal growth factor receptor (EGFR) status to one of the 2 groups: Group 1 - EGFR T790M NSCLC treated with EGF816 150 mg once daily (QD) + nivolumab 3 mg/kg every 2 weeks (Q2W), and Group 2 - EGFR wild type (wt) NSCLC treated with INC280 400 mg twice daily (BID) + nivolumab 3 mg/kg Q2W. Patients in Group 2 were subdivided into 2 subgroups based on c-Mesenchymal-epithelial transition (cMet) status: Subgroup A - high cMet (referred to as Group 2A) and Subgroup B- low cMet (referred to as Group 2B).

Patients could continue study treatment until patients experienced unacceptable toxicity that precluded any further treatment, disease progression and/or treatment was discontinued at the discretion of the investigator or withdrawal of consent, or the patient was transferred to a Novartis roll-over study or an alternative treatment option that could continue to provide study treatments. Following the approval of a protocol amendment, the maximum treatment duration for nivolumab could not exceed 2 years and patients who had received nivolumab beyond 2 years were discontinued from nivolumab treatment and continued on EGF816 or INC280 alone.

The primary objective of the trial was to estimate the clinical activity of nivolumab in combination with EGF816 or INC280.

Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer

A Phase II, Multicenter, Open-label Study of EGF816 in Combination With Nivolumab in Adult Patients With EGFR Mutated Non-small Cell Lung Cancer and of INC280 in Combination With Nivolumab in Adult Patients With cMet Positive 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

PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution.

Tumor response was based on local investigator assessment as per RECIST v1.1. ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR).

For RECIST v1.1, 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 diameter of all target lesions, taking as reference the baseline sum of diameters.

Tumor response was based on local investigator assessment as per RECIST v1.1. DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD).

For RECIST v1.1, 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 the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. The median PFS was estimated using the Kaplan-Meier method.

Tumor response was based on local investigator assessment as per RECIST v1.1

PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

The PFS rate at 3 months was estimated using the Kaplan-Meier method.

OS represents the percentage of participants who are alive after the start of study treatment. OS at 1 year was estimated using the Kaplan-Meier method.

Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs.

AE grades were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Number of participants with at least one dose reduction of EGF816, INC280 or nivolumab and number of participants with at least one dose interruption of EGF816, INC280 or nivolumab.

Dose reduction was not allowed for nivolumab in this study.

Dose intensity (mg/day) of EGF816 and INC280 was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.

Dose intensity (mg/kg biweekly) of nivolumab was calculated as actual cumulative dose in mg/kg divided by duration of exposure in days and then multiplied by 14 days (2 weeks).

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose.

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.

Nivolumab serum concentrations were assessed in samples taken at pre-dose. Pre-dose samples were collected before the next dose administration.

Any sign or symptom that occurs during the study treatment plus 100 days after last dose.

Nivolumab and EGF816

Nivolumab and INC280, High cMet

Nivolumab and INC280, Low cMet

Group 2A+2B (low and high cMet): INC280 400 mg BID + Nivolumab 3 mg/kg Q2W

Nivolumab and INC280, High+Low cMet

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Study Director

All patients who had received at least 1 dose of INC280, EGF816 or nivolumab.

Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1

Overall Response Rate (ORR) Per RECIST v1.1

Disease Control Rate (DCR) Per RECIST v1.1

Median Progression-Free Survival (PFS) Per RECIST v1.1

Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1

Overall Survival (OS) at 1 Year

Treatment-related AEs

AEs with grade 3/4

Treatment-related AEs with grade 3/4

SAEs

Treatment-related SAEs

Fatal SAEs

Treatment related fatal SAEs

AEs leading to discontinuation

Treatment-related AEs leading to discontinuation

AEs leading to dose adjustment/interruption

All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

EGF816, dose reduction

EGF816, dose interruption

INC280, dose reduction

INC280, dose interruption

Nivolumab, dose reduction

Nivolumab, dose interruption

Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab

Dose Intensity of EGF816 and INC280

Dose Intensity of Nivolumab

All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast).

Maximum Observed Plasma Concentration (Cmax) of EGF816

Time to Reach Maximum Plasma Concentration (Tmax) of EGF816

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EGF816

Minimum Observed Plasma Concentration (Cmin) of EGF816

All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile.

Maximum Observed Plasma Concentration (Cmax) of INC280

Time to Reach Maximum Plasma Concentration (Tmax) of INC280

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of INC280

Minimum Observed Plasma Concentration (Cmin) of INC280

Cycle 1 Day 1

Cycle 1 Day 15

Cycle 2 Day 1

All patients who had provided at least 1 evaluable nivolumab PK concentration. For a nivolumab PK concentration to be evaluable in pre-dose samples, a patient was required to have the sample collected before the next dose administration. Samples were not collected in Group 1 on Cycle 1 Day 1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer	NCT02323126	Non Small Cell ...	EGF816 INC280 Nivolumab	18 Years -	Novartis
Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer	NCT02323126	Non Small Cell ...	EGF816 INC280 Nivolumab	18 Years -	Novartis
Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer	NCT02323126	Non Small Cell ...	EGF816 INC280 Nivolumab	18 Years -	Novartis

Spots Global Cancer Trial Database for cmet negative nsclc