Molecular analysis of circulating tumor DNA (ctDNA) in patients (pts) with EGFR exon 20 insertion-positive (ex20ins+) advanced NSCLC treated with mobocertinib.

• DOI: 10.1200/jco.2022.40.16_suppl.9108
• Publication Date: 2022-06-06T17:20:47Z
• Authors: Sylvie Vincent; Zhenqiang Su; Veronica Bunn; Adarsh Joshi; Ziji Yu; Sampurna Chatterjee; Minakshi Guha; Pingkuan Zhang
• Keywords: Concordance; EGFR Inhibitors

9108 Background: ctDNA is an important tool to diagnose and monitor mutations in pts with non–small cell lung cancer (NSCLC). We evaluated epidermal growth factor receptor gene ( EGFR) ex20ins tumor vs plasma samples, assessed changes EGFR variant allele frequency (VAF) mobocertinib treatment correlation response, identified potential emerging variants of acquired resistance. Methods: Tumor tissue samples were collected at baseline (BL) from ex20ins+ advanced NSCLC receiving 160 mg QD a phase 1/2 study (NCT02716116); BL, after 2 cycles (Cycle 3, Day 1 [C3D1]) disease progression/end (DP/EOT). analyzed by next-generation sequencing for determine concordance rate detection between BL. Changes VAF BL C3D1 DP/EOT confirmed response (RECIST v1.1) per independent review committee. Emerging elimination germline seen healthy populations (gnomAD databases 1000 Genomes) nonharmful predicted PolyPhen SIFT tools or annotated as benign ClinVar database. Results: detected 29 38 (76%) tissue-confirmed NSCLC. VAFs significantly decreased mobocertinib-treated partial (PR; P=0.0057) stable (SD; P=0.0016), but not progressive (PD; P=0.14) (Table). EOT/DP analysis numerous genetic variants; EGFR, TP53, DNMT3A the most common genes variants. Twelve missense 9 pts, including located exon 20 loop following C-helix (6), T790M (5), D379E (1). Conclusions: Concordance was 76%. patients PR SD. Plasma longitudinal monitoring may be useful assess mutation status progression treated mobocertinib. Clinical trial information: NCT02716116. [Table: see text]