Xiuning Le, MD, PhD, spoke about which patients with advanced non–small cell lung cancer with high MET-amplification could benefit most from tepotinib based on molecular markers.
CancerNetwork® spoke with Xiuning Le, MD, PhD, at the 2022 American Society of Clinical Oncology (ASCO) Annual Meetingabout which patients with advanced non–small cell lung cancer (NSCLC) with high MET-amplification could benefit most from tepotinib (Tepmetko), according to findings from the phase 2 VISION trial cohort B (NCT02864992). Data from the trial, which used a liquid biopsy assay to detect MET amplifications and circulating tumor DNA (ctDNA) burden, highlighted that those with focal MET amplifications, who had low ctDNA burden, and low tumor burden appeared to benefit the most from treatment. Conversely, non-focal MET amplifications, MYC amplifications, and RB1 mutations were associated with worse responses, Le stated.
Targeted therapies, especially a TKI [tyrosine kinase inhibitor] using tepotinib as an example, for [patients with] high MET amplification in NSCLC, we think there is an efficacy signal clearly from cohort B of the VISION trial. From the translational or biomarker analysis from this group of patients, although small, we started to understand a little better [which] patients can benefit the most. If the tumor has a focal MET amplification, if the patient has a relatively low ctDNA burden and tumor burden, those are the characteristics that predict a good response. On the flip side, we also started to discover that MET non-focal amplification, MYC amplification, RB1 mutation, and TP53 mutations are bad players and dictate [whether] a patient’s tumor [will] potentially respond. This trial is informative, not only showing the preliminary efficacy but also guiding us forward to understand [which] patient can potentially benefit the best from this TKI approach.
Le X, Paz-Ares LG, Meerneeck JV, et al. Clinical response to tepotinib according to circulating tumor DNA biomarkers in patients with advanced NSCLC with high-level MET amplification detected by liquid biopsy. J Clin Oncol. 2022;40(suppl 16):9121. doi:10.1200/JCO.2022.40.16_suppl.9121