Osimertinib and Necitumumab in Treating Patients With EGFR-Mutant Stage IV or Recurrent Non-small Cell Lung Cancer Who Have Progressed on a Previous EGFR Tyrosine Kinase Inhibitor

Description

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of osimertinib (AZD9291) in combination with necitumumab in patients with EGFR-mutant non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVE:

I. To observe and record anti-tumor activity in these NSCLC patients in select cohorts of patients with EGFR-activating mutations including EGFR Exon 20 insertion mutations.

TRANSLATIONAL OBJECTIVES:

I. To characterize the pharmacokinetics of osimertinib (AZD9291) in combination with necitumumab.

II. To explore biomarkers of response and resistance to previous EGFR-tyrosine kinase inhibitors (TKIs) and with the combination by studying biopsied tumor tissue at baseline and at progression, as well as serial plasma deoxyribonucleic acid (DNA) specimens.

III. To create patient derived xenograft (PDX) models of patients with EGFR-mutant NSCLC both prior to study initiation and at acquired resistance to treatment.

OUTLINE: This is a dose-escalation study of necitumumab.

Patients receive osimertinib orally (PO) once daily (QD) on days 1-21 and necitumumab intravenously (IV) over 60 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) or multigated acquisition scans (MUGA) and computed tomography (CT) scan, magnetic resonance imaging (MRI) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, every 12 weeks for 1 year, and annually thereafter.