P60.12 Prevalence of c-Met overexpression (c-Met+) and Impact of Prior Lines of Treatment on c-Met Protein Expression in NSCLC

Abstract

Teliso-V, an anti–c-Met antibody conjugated with monomethyl auristatin E, is currently being investigated as monotherapy in c-Met+ 2nd/3rd-line metastatic NSCLC in a phase 2 study (NCT03539536). Here we present prevalence of c-Met+ NSCLC based on histopathology and EGFR mutation status. c-Met expression change from archival (diagnostic (Dx)/post-Dx biopsy) vs fresh (tumor biopsy at time of study prescreening) is also presented for patient subsets. In this study, patients were prospectively selected for c-Met–positive expression by immunohistochemistry (central assay; SP44 antibody). Archival or fresh tumor tissue was eligible for c-Met expression testing and enrollment consideration. Per protocol, if archival tissue was c-Met negative, patients could provide fresh tumor tissue for reassessment of c-Met expression. As of December 2020, 841 patients evaluable for c-Met expression have been prescreened (Table 1). c-Met+ rates were lower in EGFR wild-type (25%) vs mutant (37%) non-squamous cohorts. Squamous histology had a 39% positivity rate. c-Met+ rates were higher in fresh vs archival tumor tissue. Similar trends were observed when EGFR wild-type and mutant cohorts were separated based on c-Met–high or –intermediate groups (Table 2). Sixteen patients (non-squamous cohorts: EGFR mutant, N=8; EGFR wild-type, N=8) initially reported c-Met–negative status based on archived tissue and submitted fresh tissue for c-Met reassessment. Tumors from EGFR mutant (50%) and wild-type (12.5%) cohorts had changes in c-Met status from negative to positive, potentially due to prior anti-EGFR or immuno-oncology/chemotherapy treatments, degradation of the epitope over time in the sample, or heterogeneity within tumor lesions.Table 1Patientsc-Met Positive, %a (n)NSQ EGFR MU24537 (90)NSQ EGFR WT44625 (122)Squamous15039 (58)aThe c-Met–positive cutoffs (by immunohistochemistry using SP44 antibody) were derived from retrospective receiver operating characteristic analysis of phase 1 (NCT02099058) Teliso-V monotherapy data. Cutoffs were established as membrane staining: non-squamous (≥25% 3+) and squamous (≥75% 1+) NSCLC. MU, mutant; NSQ, non-squamous; WT, wild-type. Open table in a new tab aThe c-Met–positive cutoffs (by immunohistochemistry using SP44 antibody) were derived from retrospective receiver operating characteristic analysis of phase 1 (NCT02099058) Teliso-V monotherapy data. Cutoffs were established as membrane staining: non-squamous (≥25% 3+) and squamous (≥75% 1+) NSCLC. MU, mutant; NSQ, non-squamous; WT, wild-type. Based on defined cutoffs, 25%–39% of NSCLC tumors were c-Met+. Consistent with prior observations, an increase in c-Met expression was observed in tumor tissue after anti-EGFR treatments. The increase in c-Met expression following immuno-oncology/chemotherapy treatments was a new observation. Additional data are needed to make conclusive remarks.