INSIGHT 2: a Phase II Study of Tepotinib Plus Osimertinib in <i>MET</i> -Amplified NSCLC and First-Line Osimertinib Resistance
Egbert F. Smit, Christophe Dooms, Jo Raskin, Ernest Nadal, Lye Mun Tho, Xiuning Le, Julien Mazières, How Soon Hin, Masahiro Morise, Viola W. Zhu, Daniel S.W. Tan, Kristina Holmberg, Barbara Ellers‐Lenz, Svenja Adrian, Sabine Brutlach, Karl Maria Schumacher, Niki Karachaliou, Yi‐Long Wu
Abstract
MET amplification (METamp), 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 METamp-driven resistance. INSIGHT 2 (NCT03940703), an international, open-label, multicenter phase II trial, assesses tepotinib plus osimertinib in patients with advanced/metastatic EGFR-mutant NSCLC and acquired resistance to first-line osimertinib and METamp, determined centrally by fluorescence in situ hybridization (gene copy number ≥5 and/or MET/CEP7 ≥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)