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 Pharmaceuticals0 sitesJuly 24, 2018

ConditionsCarcinoma, Non-small Cell Lung

InterventionsEFG816 erlotinib or gefitinib

DrugsEFG816 erlotinib or gefitinib

Overview

Phase: Phase 3
Intervention: EFG816
Conditions: Carcinoma, Non-small Cell Lung
Sponsor: Novartis Pharmaceuticals
Primary Endpoint: Progression Free Survival (PFS) by Blinded independent review committee (BIRC)
Status: Withdrawn
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

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).

Registry

clinicaltrials.gov

Start Date

July 24, 2018

End Date

June 3, 2024

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Written informed consent obtained prior to any screening procedures.
•Histologically documented locally advanced or metastatic, stage IIIB/ IIIC or stage IV NSCLC with documented EGFR activating mutation (L858R or ex19del)
•Provision of a tumor tissue sample to allow for retrospective analysis of EGFR mutation status
•No prior treatment with any systemic antineoplastic therapy in the advanced setting
•Recovered from all toxicities related to prior treatment
•Presence of at least one measurable lesion according to RECIST 1.1
•Eastern Cooperative Oncology Group (ECOG) performance ≤1
•Meet the following laboratory values at the screening visit:
•Absolute Neutrophil Count ≥1.5 x 109/L
•Platelets ≥75 x 109/L

Exclusion Criteria

•Prior treatment with EGFR-TKI.
•Known T790M positive mutation. Any other known EGFR activating mutations other than L858R or ex19del. Patients whose tumors harbor other EGFR mutations concurrent with L858R or ex19del EGFR mutations are eligible.
•Symptomatic brain metastases
•History of interstitial lung disease or interstitial pneumonitis
•Any medical condition that would, in the investigator's judgment, the patient's in the study due to safety concerns, compliance with clinical study procedures or interpretation of study results
•Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years..
•Presence of clinically significant ophthalmologic abnormalities
•Bullous and exfoliative skin disorders of any grade
•Presence or history of microangiopathic hemolytic anemia with thrombocytopenia.
•Known history of testing positive for human immunodeficiency virus (HIV) infection

Arms & Interventions

EGF816

Investigational treatment arm of EGF816 (nazartinib).

Intervention: EFG816

Investigator's Choice

Investigator's Choice (erlotinib or gefitinib).

Intervention: erlotinib or gefitinib

Outcomes

Primary Outcomes

Progression Free Survival (PFS) by Blinded independent review committee (BIRC)

Time Frame: Approximately 3 years

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.

Secondary Outcomes

Time to progression in Central Nervous System (CNS) per central neuro-radiologist BIRC(Approximately 3 years)
Disease control rate (DCR) by central BIRC(Approximately 3 years)
CNS DoR per central neuro-radiologist BIRC(Approximately 3 years)
Charactise Plasma PK (Cmax) of EGF816(Day 1 of Cycles 1 to 6 inclusive (21 day cycle))
Charactise Plasma PK (AUC) of EGF816(Day 1 of Cycles 1 to 6 inclusive (21 day cycle))
Charactise Plasma PK (t1/2) of EGF816(Day 1 of Cycles 1 to 6 inclusive (21 day cycle))
Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-C30 Questionnaire(Approximately 4 years)
PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1(Approximately 4 years)
Overall response rate (ORR) by central BIRC(Approximately 3 years)
Duration of response (DOR) by central BIRC(Approximately 3 years)
Time to response (TTR) by central BIRC(Approximately 3 years)
CNS ORR per central neuro-radiologist BIRC(Approximately 3 years)
Overall Survival(Approximately 6 years)
Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by QLQ-LC13 Questionnaire(Approximately 4 years)
Patient Reported Outcome: Health Related Quality of Life (HRQoL) as measured by EuroQoL-5 Dimension-5 (EQ-5D-5L) Questionnaire(Approximately 4 years)
PFS by investigator(Approximately 3 years)