1. 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
- Author
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Philippe Barthélémy, Samson Fung, Valérie Hanssens, Christian Rolfo, Luc Van Rompaey, Virginia Morello, Manuela Cazzanti, Ahmad Awada, Natalie De Jonge, Sylvie Rottey, Adeline Bouard, Christophe Borg, Philippe Aftimos, Jean-René Pallandre, and Paolo Michieli
- Subjects
0301 basic medicine ,Antibody-dependent cell-mediated cytotoxicity ,Cancer Research ,Tumor microenvironment ,business.industry ,Phase i study ,Blockade ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Ascites ,Myeloid-derived Suppressor Cell ,Cancer research ,medicine ,In patient ,medicine.symptom ,business ,Clin oncol - 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...
- Published
- 2016