Osimertinib With Ramucirumab in EGFR-mutated, T790M-positive Patients With Progression During EGFR-TKI Therapy: Phase Ib Study

Abstract

BackgroundEpidermal growth factor receptor (EGFR) T790M mutation is the most frequent mechanism of resistance among patients with progression during EGFR-tyrosine kinase inhibitor (TKI) therapy. A third-generation EGFR-TKI, osimertinib, demonstrated durable efficacy with mild adverse events in a phase III trial and is considered a novel standard regimen. The tolerability of osimertinib monotherapy has allowed for the development of a more efficacious combination regimen. Preclinical and clinical study data have suggested that vascular endothelial growth factor inhibition can enhance EGFR-TKI activity with tolerable toxicity. AimsThe aim of the present single-arm, phase Ib study is to assess the tolerability of osimertinib combined with ramucirumab in patients with EGFR-mutated, T790M+ lung cancer with progression during EGFR-TKI therapy. The primary endpoint is to assess the safety of osimertinib plus ramucirumab at a fixed dose. The secondary endpoints are the overall response rate, progression-free survival, overall survival, and safety. Six patients will be enrolled in the trial.