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

NCT03529084 | Withdrawn Phase 3 DMC FDA Drug

• 2 other identifiers: CEGF816A23022017-003998-34
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Carcinoma, Non-small Cell Lung

Keywords

Non small cell lung cancer; NSCLC; EGFR mutation; EGF816; nazartinib; erlotinib; gefitinib

Outcome Measures

Primary Outcomes (1)

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

  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.

  Approximately 3 years

Secondary Outcomes (16)

• Overall Survival

  Approximately 6 years

• PFS by investigator

  Approximately 3 years

• PFS after next-line of treatment (PFS2) using investigator assessment according to RECIST 1.1

  Approximately 4 years

• Time to progression in Central Nervous System (CNS) per central neuro-radiologist BIRC

  Approximately 3 years

• Overall response rate (ORR) by central BIRC

  Approximately 3 years

Study Arms (2)

EGF816

EXPERIMENTAL

Investigational treatment arm of EGF816 (nazartinib).

Drug: EFG816

Investigator's Choice

ACTIVE COMPARATOR

Investigator's Choice (erlotinib or gefitinib).

Drug: erlotinib or gefitinib

Interventions

EFG816 DRUG

It will be administered orally daily.

Also known as: nazartinib

EGF816

erlotinib or gefitinib DRUG

Investigator's choice between erlotinib or gefitinib. These will be locally sourced. Erlotinib will be administered orally daily. Gefitinib will be administered orally daily.

Investigator's Choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Hemoglobin (Hgb) ≥9 g/dL
• Creatinine Clearance ≥ 45 mL/min using Cockcroft-Gault formula
• Total bilirubin ≤1.5 x ULN
• Aspartate transaminase (AST) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if AST ≤5.0 x ULN
• Alanine transaminase (ALT) ≤ 3.0 x ULN, except for patients with liver metastasis, who may only be included if ALT ≤5.0 x ULN

You may not qualify if:

• 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
• Cardiac or cardiac repolarization abnormality
• Major surgery: ≤4 weeks to starting study treatment or who have not recovered from side effects of such procedure.
• Unable or unwilling to swallow tablets or capsules
• Female patients who are either pregnant or nursing
• Women of child bearing potential who refuse or are not able to use a highly effective method of contraception as defined in the study protocol.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

nazartinib; Erlotinib Hydrochloride; Gefitinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: blinded independent review committee for primary endpoint of PFS
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 18, 2018
• Study Start: July 24, 2018
• Primary Completion: August 13, 2020
• Study Completion: June 3, 2024
• Last Updated: November 22, 2019

Record last verified: 2019-11