First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients

Therapeutic Advances in Medical Oncology
Seung Tae KimJeeyun Lee

Abstract

YYB101, a humanized monoclonal antibody against hepatocyte growth factor (HGF), has shown safety and efficacy in vitro and in vivo. This is a first-in-human trial of this antibody. YYB101 was administered intravenously to refractory cancer patients once every 4 weeks for 1 month, and then once every 2 weeks until disease progression or intolerable toxicity, at doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamics were studied. HGF, MET, PD-L1, and ERK expression was evaluated for 9 of 17 patients of the expansion cohort (20 mg/kg). In 39 patients enrolled, no dose-limiting toxicity was observed at 0.3 mg/kg, and the most commonly detected toxicity was generalized edema (n = 7, 18.9%) followed by pruritis and nausea (n = 5, 13.5%, each), fatigue, anemia, and decreased appetite (n = 4, 10.8%, each). No patient discontinued treatment because of adverse events. YYB101 showed dose-proportional pharmacokinetics up to 30 mg/kg. Partial response in 1 (2.5%) and stable disease in 17 (43.5%) were observed. HGF, MET, PD-L1, and ERK proteins were not significant predictors for treatment response. However, serum HGF level was significantly l...Continue Reading

References

Jan 21, 1997·Proceedings of the National Academy of Sciences of the United States of America·H TakayamaG Merlino
Jun 6, 2003·Nature·Donald P Bottaro, Lance A Liotta
Nov 14, 2008·Molecular Biology of the Cell·Maria Cristina StellaPaolo M Comoglio
Jun 19, 2010·Regulatory Toxicology and Pharmacology : RTP·Jay TibbittsJohn T Sullivan
Jan 25, 2012·Nature Reviews. Cancer·Ermanno GherardiGeorge Vande Woude
Mar 5, 2013·Cancer Treatment Reviews·Giorgio V ScagliottiJoachim von Pawel
Jun 29, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Sang Y HaKyoung-Mee Kim
Oct 1, 2014·Cancers·Makiko Kawaguchi, Hiroaki Kataoka
Jan 12, 2016·MAbs·Sameer A GreenallTerrance G Johns
Mar 25, 2017·Experimental & Molecular Medicine·Hyori KimIn-Hoo Kim
Apr 20, 2017·Cancers·Benjamin Yaw OwusuLidija Klampfer
Oct 6, 2017·Cancer Discovery·Eirini PectasidesDaniel V Catenacci
Feb 7, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·S T KimJ Lee
Mar 27, 2018·Clinical Colorectal Cancer·Su Jin LeeSeung Tae Kim
May 19, 2019·Nature Chemical Biology·Katsuya SakaiKunio Matsumoto
Jun 20, 2019·International Journal of Molecular Sciences·Nawaphat JangphattananontKunio Matsumoto

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Citations

Dec 5, 2020·International Journal of Molecular Sciences·Srinivasa P PothulaMinoti V Apte
Sep 21, 2021·EMBO Molecular Medicine·Morgan BrissetFrédéric Hollande

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Methods Mentioned

BETA
xenograft
ELISA
biopsies
biopsy

Clinical Trials Mentioned

NCT02499224

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