Abstract 3385: Liquid biopsy to detect MET exon 14 skipping (METex14) and MET amplification in patients with advanced NSCLC: Biomarker analysis from VISION study
Authors: Le Xiuning , Kowalski Dariusz , Cho Byoung Chul , Conte Pierfranco , Felip Enriqueta , Garassino Marina Chiara , Viteri Santiago , Chang Gee-Chen , Richart John , Paz-Ares Luiz , Juraeva Dilafruz , Straub Josef , Stroh Christopher , Paik Paul 
Published: September 2020

Purpose: In the ongoing, single-arm, Phase 2 VISION study (NCT02864992), tepotinib (a highly selective MET inhibitor) has shown durable clinical activity in NSCLC patients (pts) with METex14 skipping. Here, we report the biomarker profile of pts screened with liquid biopsy (LBx) for inclusion in the study.

Methods: Pts with advanced NSCLC and previously confirmed EGFR/ALK wild-type status were prospectively screened for MET alterations using plasma samples collected during pre-screening/screening. Plasma ctDNA sequencing was performed at a central laboratory using a 73-gene next-generation sequencing panel (Guardant360®).

Results: Of 6,034 pts screened, 813 pts had results pending at data cut and of 5,221 pts tested, sequencing failed in 41 pts. The success rate of LBx testing was consistent across centers. Of 5,180 patients analyzed, 694 pts (13.4%) had no mutation detected. Despite the intent of screening EGFR/ALK wild-type pts, 327 pts (6.3%) had EGFR mutations and 49 (0.9%) had ALK/ROS fusions. 188 pts (3.6%) had METex14 skipping (Table) and 256 pts (4.9%) had MET amplification (amp) without METex14 skipping. The median age of METex14 pts was 72 years; 47% were male; 46% were never smokers and 65% had adenocarcinoma histology. In METex14 pts, the most frequently occurring driver co-alterations were amp in MET (13.3%), EGFR (7.4%), CDK4 (6.4%), BRAF (5.3%) and CDK6 (4.8%), and mutations in GNAS (5.3%). In METamp pts, the most frequently occurring driver co-alterations were CDK6 (60.5%), BRAF (43.4%), EGFR (28.9%), MYC (21.9%) and CCNE1 (19.9%) amps. Overall, TP53 mutations were detected in 55.9% of METex14 pts and 79.7% of METamp pts.

Table:Characterization of METex14 skipping (n=188)n (%)Insertions/deletions (indels)93 (49.5)Indel at acceptor site54 (28.7)Indel at donor site36 (19.1)Whole exon 14 deletion3 (1.6)Single nucleotide variation (SNV)95 (50.5)SNV at donor site93 (49.5)SNV at acceptor site2 (1.1)SNVs and indelsSNV/indel at donor site129 (68.6)SNV/indel at acceptor site56 (29.8)SNV/indel whole exon 14 deletion3 (1.6)

Conclusions: In this population, METex14 skipping can be successfully detected through non-invasive LBx analysis using a next-generation sequencing panel. The rate of METex14 skipping and the genomic profile and demographics of pts were similar to previously reported data.

Citation Format: Xiuning Le, Dariusz Kowalski, Byoung Chul Cho, Pierfranco Conte, Enriqueta Felip, Marina Chiara Garassino, Santiago Viteri, Gee-Chen Chang, John Richart, Luiz Paz-Ares, Dilafruz Juraeva, Josef Straub, Christopher Stroh, Paul Paik. Liquid biopsy to detect MET exon 14 skipping (METex14) and MET amplification in patients with advanced NSCLC: Biomarker analysis from VISION study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3385.