A phase 1/2 study of REGN5093-M114, a METxMET antibody-drug conjugate, in patients with mesenchymal epithelial transition factor (MET)-overexpressing NSCLC

• Published in: Journal of clinical oncology Vol. 40; no. 16_suppl; p. TPS8593
• Main Authors: Drilon, Alexander E., Awad, Mark M., Gadgeel, Shirish M., Villaruz, Liza C, Sabari, Joshua K., Perez, Javier, Daly, Christopher, Patel, Shraddha, Li, Siyu, Seebach, Frank A., Lowy, Israel, Magnan, Heather D., Rietschel, Petra
• Format: Journal Article
• Language: English
• Published: 01-06-2022
• DOI: 10.1200/JCO.2022.40.16_suppl.TPS8593
• EISSN: 1527-7755
• ISSN: 0732-183X

TPS8593
Background: MET, also called hepatocyte growth factor receptor (HGFR), is a high-affinity transmembrane protein receptor for HGF. MET is overexpressed in various malignancies, including non-small cell lung cancer (NSCLC). MET overexpression can accompany MET exon 14 alteration or de novo/acquired MET amplification. REGN5093-M114 is an antibody drug conjugate composed of a novel linker-payload (M114, carrying the maytansine derivative M24, a potent inhibitor of microtubule assembly) covalently bound to lysine residues on a MET-targeting human IgG4p bispecific antibody, REGN5093. In preclinical models of MET overexpressing cancers, REGN5093-M114 demonstrated significant dose-dependent antitumor activity. Methods: This is an open label, phase 1/2, first-in-human, multicenter dose-escalation study with cohort expansion evaluating REGN5093-M114 in patients with MET-overexpressing NSCLC (NCT04982224). Patients must have advanced stage NSCLC for which there are no approved therapies available expected to confer clinical benefit, with tumor overexpressing MET (≥75% tumor cell staining at 2+) as centrally confirmed by immunohistochemistry. For the expansion phase, patients must have at least one lesion that is measurable by RECIST 1.1. REGN5093-M114 will be administered intravenously once every 3 weeks over 30 minutes until disease progression, intolerable adverse events, withdrawal of consent, or study withdrawal. The primary objectives in dose escalation are to evaluate safety, tolerability, PK, and maximum tolerated dose and/or recommended phase 2 dosing regimen of REGN5093-M114. PKs will include the assessment of REGN5093-M114, total antibody, and payload M24 concentrations. The primary objective in dose expansion is to assess preliminary anti-tumor activity of REGN5093-M114 in MET-overexpressing NSCLC as measured by the objective response rate. The secondary objectives of both phases of the study include an evaluation of treatment durability, and the immunogenicity of REGN5093-M114. This study is currently open to enrollment. Clinical trial information: NCT04982224.