LBA50 - Mechanisms of acquired resistance to first-line osimertinib: preliminary data from the phase III FLAURA study
Suresh S. Ramalingam (Atlanta, US)
In the phase 3 FLAURA study, osimertinib showed efficacy in patients (pts) with previously untreated EGFRm (epidermal growth factor receptor mutant) advanced NSCLC compared to standard of care (SoC). This abstract reports on the mechanisms of acquired resistance to osimertinib experienced by pts who progressed on the FLAURA study. In line with previous analyses, T790M was acquired in approximately 50% of SoC-treated pts, and none of the osimertinib‑treated pts; no unexpected resistance mechanisms were observed in osimertinib-treated pts. Exploration into novel acquired mutations is ongoing.
LBA52 - Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients (pts) with METΔex14 mutated advanced non-small cell lung cancer (NSCLC)
Juergen Wolf (Cologne, DE)
MET mutations leading to exon 14 deletion (METΔex14) occur in 3-4% of NSCLCs. Capmatinib is a highly potent and selective MET inhibitor and GEOMETRY mono-1 is a multi-cohort, multicenter study (NCT02414139), evaluating capmatinib in pts with METΔex14 mutated or MET amplified advanced NSCLC. In this study, Capmatinib has demonstrated a clinically meaningful response rate and a manageable toxicity profile in pts with METΔex14 mutated NSCLC, particularly in treatment naive pts where the ORR by BIRC (blinded imaging review committee) is 72%.
1377O - Phase 2 study of tepotinib + gefitinib (TEP+GEF) in MET-positive (MET+)/epidermal growth factor receptor (EGFR)-mutant (MT) non-small cell lung cancer (NSCLC)
Yi-Long Wu (Guangzhou, CN)
Patients with NSCLC can acquire resistance to EGFR tyrosine kinase inhibitors (EGFR TKIs) via MET activation, therefore dual MET/EGFR inhibition may have potential in EGFR TKI-resistant NSCLC. Tepotinib (TEP) is a potent, selective MET TKI and gefitinib (GEF) is an EGFR inhibitor. According to the results of this phase 2 study, the tepotinib + gefitinib combination (TEP+GEF) shows promising antitumor activity in pts with MET protein overexpression (IHC3+) and gene amplification EGFR-MT NSCLC. TEP + GEF was well-tolerated in this study.