P47.03 Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met+ Advanced Non-Small Cell Lung Cancer: Stage 2

Abstract

Telisotuzumab vedotin (Teliso-V) is an anti-c-Met antibody conjugated with a tubulin inhibitor, monomethylauristatin E. The c-Met receptor tyrosine kinase is the cell surface receptor for hepatocyte growth factor (HGF) encoded for by the MET proto-oncogene. c-Met overexpression occurs in various solid tumors, including non-small cell lung cancer (NSCLC), and the aberrant activation of the c-Met/HGF axis contributes to tumor progression, angiogenesis, invasive growth, metastasis, and resistance to therapies. Following encouraging evidence of anti-tumor activity in a Phase 1 study (Strickler et al. J Clin Oncol 2018;36:3298–3306), a Phase 2 study was initiated to explore the safety and efficacy of Teliso-V monotherapy in 3 cohorts (based on histopathology and epidermal growth factor receptor [EGFR] mutation) and 5 subgroups (based on c-Met expression) of patients with c-Met+ advanced NSCLC (study Stage 1), followed by expansion into an appropriately selected population based on study Stage 1 results for further evaluation of safety and efficacy (study Stage 2). This Phase 2, non-randomized, single-arm, adaptive study (NCT03539536) is enrolling patients aged ≥18 years with Eastern Cooperative Oncology Group performance status ≤1 and locally advanced or metastatic c-Met+ NSCLC who have received 1–2 prior lines of therapy (including systemic chemotherapy, immunotherapy, and targeted therapy, if eligible). Based on data from study Stage 1 (Camidge et al. AACR 2021), the cohort of patients with non-squamous EGFR wild type c-Met+ NSCLC met prespecified criteria to transition to the study Stage 2 single-arm expansion cohort. Study Stage 2 enrollment commenced in February 2021 and is ongoing; up to approximately 160 patients will be enrolled in study Stage 2. c-Met status is determined centrally by immunohistochemistry. The primary endpoint is overall response rate per independent central review (based on Response Evaluation Criteria in Solid Tumors version 1.1). Secondary endpoints are duration of response, disease control rate, progression-free survival, and overall survival. Quality of life will be evaluated as an exploratory efficacy endpoint and safety and tolerability will be assessed. Pharmacokinetic and biomarker samples will also be collected for analysis. Teliso-V is administered as a 30±10 min intravenous infusion at a dose of 1.9 mg/kg every 2 weeks until disease progression or study discontinuation criteria are met. ▪▪▪ ▪▪▪