First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients. (June 2020)

• Record Type: Journal Article
• Authors: Kim, Seung Tae; Hong, Jung Yong; Park, Se Hoon; Park, Joon Oh; Park, Young Whan; Park, Neunggyu; Lee, Hukeun; Hong, Sung Hee; Lee, Song-Jae; Song, Seong-Won; Kim, Kyung; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Nam, Do-Hyun; Lee, Jeong-Won; Park, Keunchil; Kim, Kyoung-Mee; Lee, Jeeyun
• Is Part Of: Therapeutic advances in medical oncology. Volume 12(2020)
• Publication Date: 2020-06
• Subjects: hepatocyte growth factor -- pharmacodynamics -- pharmacokinetics -- phase I -- refractory cancer; Oncology -- Periodicals; Cancer -- Treatment -- Periodicals; 616.994005
• DOI: 10.1177/1758835920926796
• Languages: English
• ISSNs: 1758-8340

Abstract

Background: 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. Materials and Methods: 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). Results: 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 lowered in responders upon drug administration. RNA sequencing revealed a mesenchymal signature in two long-term responders. Conclusion: YYB101 showed favorable safety and efficacy in patients with refractory solid tumors. Based on this phase I trial, a phase II study on the YYB101 + irinotecan combination in refractory metastatic colorectal cancer patients is planned. Conclusion: ClinicalTrials.gov Identifier: NCT02499224