ARGX-111 shows activity in MET-amplified patients in a phase-I study and in preclinical models of myeloid-derived suppressor cell (MDSC) depletion in the tumor microenvironment.

Abstract

e14016Background: ARGX-111 is a therapeutic antibody candidate combining three independent MoA: i. blockade of HGF-dependent and -independent MET activity, ii. enhanced ADCC and iii. increased tissue penetration through enhanced FcRn binding. A Phase-I study (NCT02055066) in patients with c-MET-amplified tumors is ongoing. A new hypothesis for depletion of MET-positive MDSCs in the tumor microenvironment is also investigated. Methods: c-MET amplification detected using FISH on tumor biopsies is a prescreening requisite for patient selection in the expansion phase. MDSCs were enumerated by FACS using blood and ascites from patients or tumor and spleen tissue from a mouse CT26 syngeneic tumor model. Results: ARGX-111 dose escalation indicated a favorable safety profile and fixed a 3 mg/kg bi-weekly dose for the safety expansion in c-MET-amplified patients. Efficacy signals were seen in the c-MET-amplified setting [J Clin Oncol 33, 2015 (suppl; abstr 2580)]. FISH screening identified 4% of c-MET-amplified bi...