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

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).

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
  • 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

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
• 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.
• Sexually active males unless they use a condom during intercourse while taking drug and for 3 months after the last dose of study treatment.

Other protocol-defined inclusion/exclusion criteria may apply