Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B

• Published in: Cell reports. Medicine 2023-11, Vol.4 (11), p.101280-101280, Article 101280
• Main Authors: Le, Xiuning, Paz-Ares, Luis G, Van Meerbeeck, Jan, Viteri, Santiago, Galvez, Carlos Cabrera, Smit, Egbert F, Garassino, Marina, Veillon, Remi, Baz, David Vicente, Pradera, Jose Fuentes, Sereno, María, Kozuki, Toshiyuki, Kim, Young-Chul, Yoo, Seung Soo, Han, Ji-Youn, Kang, Jin-Hyoung, Son, Choon-Hee, Choi, Yoon Ji, Stroh, Christopher, Juraeva, Dilafruz, Vioix, Helene, Bruns, Rolf, Otto, Gordon, Johne, Andreas, Paik, Paul K
• Format: Article
• Language: English
• Subjects: Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Humans; Liquid Biopsy; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Pyrimidines
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2023.101280

High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).