1397P Prevalence, molecular characterization, and prognosis of MET–overexpressing non-small cell lung cancer (NSCLC) in a real-world patient cohort

Antibody-drug conjugates (ADCs) may extend targeted therapy to patients (pts) whose tumors express an antigen regardless of the presence of a driver mutation. Telisotuzumab vedotin (ABBV-399), a first-in-class MET (or c-Met)-directed ADC, had promising monotherapy anticancer activity in previously treated pts with MET-overexpressing (OE), non-squamous EGFR wild type NSCLC (Camidge et al. JCO. 2022;40:16 suppl, 9016). Characterization of MET OE NSCLC, a novel biomarker-defined therapeutically relevant subgroup, is thus warranted. MET OE was evaluated in a real-world cohort and co-associated with mRNA expression, MET gene amplification (METamp) and mutations, and outcomes to understand prognosis of MET OE NSCLC. The cohort comprised treated pts with stage IV NSCLC seeking care at City of Hope National Medical Center in ≥2016 and had tissue adequate for MET immunohistochemistry (IHC). MET OE was determined using anti-MET clone SP44 IHC assay (Roche Tissue Diagnostics; positive if ≥25% cells at 3+ intensity). MET FISH, RNAseq, and whole exome sequencing were conducted. Clinical data were extracted from electronic health records, and unadjusted hazard ratios from 1L treatment initiation until death or censoring were calculated. Pts receiving targeted therapy in 1L were excluded. 84 pts were included; 77% had samples taken prior to metastatic spread. 21 (25%) were MET OE positive. MET OE was not associated with history of smoking. METamp was found in 5/69 tumors evaluated (9%); of these, 2 were MET OE. Only 2 pts had MET mutations; neither were exon 14 skipping and one was MET OE. MET mRNA, evaluated in 58 cases, was 4-fold higher in MET OE NSCLC vs not OE. 1L regimens used were chemotherapy (52.4%), chemotherapy + immune checkpoint inhibitor (ICI; 26.2%), or ICI (21.4%). The unadjusted hazard ratio for death in pts with MET OE NSCLC vs not OE was 2.04 (95% CI: 1.02, 4.10). Pts with MET OE NSCLC had worse prognosis compared with those without MET OE, when treated with standard of care including ICI. Given the development of MET-directed ADCs, MET OE (distinct from METamp) may be a future target for characterization and treatment of NSCLC.