@article{5e4c4075ecc34b07b6e4574535f0eef2,
title = "The nhance{\textregistered} mutation-equipped anti-met antibody argx-111 displays increased tissue penetration and anti-tumor activity in advanced cancer patients",
abstract = "Dysregulation of MET signaling has been implicated in tumorigenesis and metastasis. ARGX-111 combines complete blockade of this pathway with enhanced tumor cell killing and was investigated in 24 patients with MET-positive advanced cancers in a phase 1b study at four dose levels (0.3–10 mg/kg). ARGX-111 was well tolerated up to 3 mg/kg (MTD). Anti-tumor activity was observed in nearly half of the patients (46%) with a mean duration of treatment of 12 weeks. NHance{\textregistered} mutations in the Fc of ARGX-111 increased affinity for the neonatal Fc receptor (FcRn) at acidic pH, stimulating transcytosis across FcRn-expressing cells and radiolabeled ARGX-111 accumulated in lymphoid tissues, bone and liver, organs expressing FcRn at high levels in a biodistribution study using human FcRn transgenic mice. In line with this, we observed, in a patient with MET-amplified (>10 copies) gastric cancer, diminished metabolic activity in multiple metastatic lesions in lymphoid and bone tissues by 18F-FDG-PET/CT after two infusions with 0.3 mg/kg ARGX-111. When escalated to 1 mg/kg, a partial response was reached. Furthermore, decreased numbers of CTC (75%) possibly by the enhanced tumor cell killing witnessed the modes of action of the drug, warranting further clinical investigation of ARGX-111.",
keywords = "18F-FDG-PET/CT, Antibody, Cancer, MET",
author = "Philippe Aftimos and Christian Rolfo and Sylvie Rottey and Philippe Barth{\'e}l{\'e}my and Christophe Borg and Keunchil Park and Do-Youn Oh and Sang-We Kim and {de Jonge}, Natalie and Val{\'e}rie Hanssens and Karen Zwanenpoel and Carla Molthoff and Dani{\"e}lle Vugts and Torsten Dreier and Peter Verheesen and {van Dongen}, {Guus A. M. S.} and Julie Jacobs and {van Rompaey}, Luc and Anna Hultberg and Paolo Michieli and Patrick Pauwels and Samson Fung and Alain Thibault and {de Haard}, Hans and Nicolas Leupin and Ahmad Awada",
note = "Funding Information: Conflicts of Interest: N.D.J., V.H., T.D., J.J., L.V.R., A.H., A.T., H.d.H. and N.L. are all present or former employees of argenx. S.F. and P.M. were former consultants to argenx. P.A. is an employee/paid consultant for Servier, Amcure, Novartis, Roche, Macrogenics, Boehringer Ingleheim, Radius, De-loitte, G1 Therapeutics, receives honoraria from Synthon, Amgen, Novartis Gilead; receives other remuneration from Amgen, MSD, Pfizer and Roche. C.B. is a consultant for Sanofi, received honoraria from Bayer, MSD, Roche, Servier and a research Grant from Roche. P.B. reports being on the advisory boards of Bristol Myers Squibb, Ipsen, Janssen, MSD, Novartis, Pfizer and Roche and receiving honoraria from Astellas, EUSA Pharma and Sanofi. A.A. has undertaken advisory roles and received speaker fees from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Eli Lilly, Genomic Health, Roche, Ipsen, Leo Pharma, Merck, MSD, Seattle Genetics, Daiichi Novartis and Pfizer. S.-W.K. has received research funding and fees for consulting or advisory roles from AstraZeneca. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jun,
day = "1",
doi = "https://doi.org/10.3390/biomedicines9060665",
language = "English",
volume = "9",
journal = "Biomedicines",
issn = "2227-9059",
publisher = "MDPI AG",
number = "6",
}