INSIGHT 2: a Phase II Study of Tepotinib Plus Osimertinib in <i>MET</i> -Amplified NSCLC and First-Line Osimertinib Resistance

Abstract

<i>MET</i> amplification <i>(MET</i>amp), a mechanism of acquired resistance to EGFR tyrosine kinase inhibitors, occurs in up to 30% of patients with non-small-cell lung cancer (NSCLC) progressing on first-line osimertinib. Combining osimertinib with a MET inhibitor, such as tepotinib, an oral, highly selective, potent MET tyrosine kinase inhibitor, may overcome <i>MET</i>amp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic <i>EGFR</i>-mutant NSCLC and acquired resistance to first-line osimertinib and <i>MET</i>amp, determined centrally by fluorescence <i>in situ</i> hybridization (gene copy number ≥5 and/or <i>MET/CEP7</i> ≥2) at time of progression. Patients will receive tepotinib 500 mg (450 mg active moiety) plus osimertinib 80 mg once-a-day. The primary end point is objective response, and secondary end points include duration of response, progression-free survival, overall survival and safety. Trial registration number: NCT03940703 (clinicaltrials.gov).