A phase I/II study of REGN5093, a MET x MET bispecific antibody, in patients with MET-altered advanced non-small cell lung cancer (NSCLC).

TPS9628 Background: Mesenchymal-epithelial transition (MET) factor is a transmembrane tyrosine kinase receptor activated by hepatocyte growth factor (HGF). Aberrant activation of MET via gene amplification or gene mutations, as well as MET protein overexpression, has been reported in NSCLC and other cancer types and can promote tumorigenesis. REGN5093 is a human bispecific antibody that binds to two distinct epitopes of MET, blocking HGF binding and inducing internalization and degradation of MET. REGN5093 prevents MET-mediated signaling and inhibits growth of MET-driven tumor cells without inducing MET-driven biological responses (DaSilva et al, CCR, 2019; PMID: 31848185). Methods: This Phase I/II, first-in-human, multicenter study is investigating the safety, tolerability, pharmacokinetics (PK), and efficacy of REGN5093 in patients with MET-altered advanced NSCLC who have received all available approved therapies (NCT04077099). Key eligibility criteria include age ≥18 years, Eastern Cooperative Oncology Group performance status of ≤1, and documented presence of either MET exon 14 gene mutation and/or MET gene amplification and/or elevated MET protein expression. Patients are required to provide a biopsy during screening for assessment of MET biomarkers. Key exclusion criteria include prior MET-targeted biologic therapy (expansion cohorts only). Prior therapy with tyrosine kinase inhibitors are not exclusionary in any part of the study. For each patient, the study comprises a screening period of up to 28 days, followed by 3-week cycles of REGN5093 monotherapy. Study treatment will continue until confirmed disease progression or other protocol-defined reason for discontinuation. The study has two parts: dose escalation and dose expansion. Dose escalation will proceed via 4+3 design until a maximum-tolerated dose is reached or a recommended Phase II dose selected. The primary objective of the dose escalation part is to assess safety (incidence and severity of adverse events and Grade ≥3 laboratory abnormalities), tolerability (incidence of dose-limiting toxicities), and PK of REGN5093. During the expansion phase, patients will be allocated to cohorts according to the type(s) of documented biomarkers of MET-altered disease. Anti-tumor activity based on objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, determined by CT or MRI, will be the primary endpoint in the expansion cohorts. The study is currently open for enrollment. Clinical trial information: NCT04077099 .