Open AccessINSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance
Author(s) -
Egbert F. Smit,
Christophe Dooms,
Jo Raskin,
Ernest Nadal,
Lye Mun Tho,
Xiuning Le,
Julien Mazières,
How Soon Hin,
Masanori Morise,
Viola W. Zhu,
Daniel S.W. Tan,
Kristina Holmberg,
B. Ellers-Lenz,
Svenja Adrian,
Sabine Brutlach,
Karl Schumacher,
Niki Karachaliou,
YiLong Wu
Publication year - 2022
Publication title -
future oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.857
H-Index - 72
eISSN - 1744-8301
pISSN - 1479-6694
DOI - 10.2217/fon-2021-1406
Subject(s) - osimertinib , medicine , clinical endpoint , acquired resistance , lung cancer , oncology , phases of clinical research , cancer research , clinical trial , epidermal growth factor receptor , cancer , erlotinib
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)