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BACKGROUND/AIMHepatocyte growth factor (HGF) acts as a key regulator in promoting ovarian cancer metastasis. Previously, we observed that YYB-101, a humanized anti-HGF antibody, effectively inhibits ovarian cancer cell migration, invasion, and progression. Here, we evaluated the signaling mechanisms affected by YYB-101 that are important in ovarian cancer cell progression.MATERIALS AND METHODSUsing cell migration, invasion and proliferation assays, we evaluated the effects of YYB-101 on A2780/luc and SKOV3 cells. The effects of YYB-101 on signaling molecules were determined by immunocytochemistry and immunoblot analysis.RESULTSYYB-101 inhibited HGF-induced ovarian cancer cell motility by down-regulating paxillin phosphorylation and actin-cytoskeleton rearrangement. Also, YYB-101 inhibited ovarian cancer cell proliferation by reducing c-MET phosphorylation and activating apoptosis in vitro and in vivo. These effects were significantly enhanced by combining YYB-101 treatment with paclitaxel, a standard chemotherapy drug.CONCLUSIONYYB-101 can be examined as a new therapeutic agent for the treatment of patients with ovarian cancer.

01 Jan 2020·Therapeutic Advances in Medical OncologyQ2 · MEDICINE

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

Q2 · MEDICINE

ArticleOA

Author: Lee, Jeeyun ; Park, Neunggyu ; Hong, Sung Hee ; Kim, Kyoung-Mee ; Park, Joon Oh ; Kim, Seung Tae ; Kang, Won Ki ; Lee, Jeong-Won ; Nam, Do-Hyun ; Park, Se Hoon ; Park, Young Whan ; Park, Keunchil ; Lee, Song-Jae ; Hong, Jung Yong ; Kim, Kyung ; Lim, Ho Yeong ; Lee, Hukeun ; Song, Seong-Won ; Park, Young Suk

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

14 Feb 2019·Neuro-OncologyQ1 · MEDICINE

Identification of genomic and molecular traits that present therapeutic vulnerability to HGF-targeted therapy in glioblastoma

Q1 · MEDICINE

Article

Author: Sa, Jason K ; Shin, Hyemi ; Joo, Kyeung Min ; Lee, Mijeong ; Song, Seong-Won ; Nam, Do-Hyun ; Koo, Harim ; Hong, Sung Hee ; Park, Young-Whan ; Cho, Hee Jin ; Lee, Jin-Ku ; Lee, Song-Jae ; Kim, Donggeon ; Shin, Yong Jae ; Kim, Sung Heon ; Kim, Jung Yong ; Kang, Wonyoung

BACKGROUNDCancer is a complex disease with profound genomic alterations and extensive heterogeneity. Recent studies on large-scale genomics have shed light on the impact of core oncogenic pathways, which are frequently dysregulated in a wide spectrum of cancer types. Aberrant activation of the hepatocyte growth factor (HGF) signaling axis has been associated with promoting various oncogenic programs during tumor initiation, progression, and treatment resistance. As a result, HGF-targeted therapy has emerged as an attractive therapeutic approach. However, recent clinical trials involving HGF-targeted therapies have demonstrated rather disappointing results. Thus, an alternative, in-depth assessment of new patient stratification is necessary to shift the current clinical course.METHODSTo address such challenges, we have evaluated the therapeutic efficacy of YYB-101, an HGF-neutralizing antibody, in a series of primary glioblastoma stem cells (GSCs) both in vitro and in vivo. Furthermore, we performed genome and transcriptome analysis to determine genetic and molecular traits that exhibit therapeutic susceptibility to HGF-mediated therapy.RESULTSWe have identified several differentially expressed genes, including MET, KDR, and SOX3, which are associated with tumor invasiveness, malignancy, and unfavorable prognosis in glioblastoma patients. We also demonstrated the HGF-MET signaling axis as a key molecular determinant in GSC invasion, and we discovered that a significant association in HGF expression existed between mesenchymal phenotype and immune cell recruitment.CONCLUSIONSUpregulation of MET and mesenchymal cellular state are essential in generating HGF-mediated therapeutic responses. Our results provide an important framework for evaluating HGF-targeted therapy in future clinical settings.

100 Deals associated with Umikibart

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 2	KR	Cell Lab MedStartup	-
Ovarian Cancer	Preclinical	KR	Cell Lab MedStartup	04 Jul 2023
Pancreatic Cancer	Preclinical	KR	Cell Lab MedStartup	04 Jul 2023
Colorectal cancer recurrent	Preclinical	KR	Yooyoung Pharm Co. Ltd.	09 Aug 2019
Colorectal cancer recurrent	Preclinical	KR	Cell Lab MedStartup	09 Aug 2019
Metastatic Colorectal Carcinoma	Preclinical	KR	Cell Lab MedStartup	09 Aug 2019
Metastatic Colorectal Carcinoma	Preclinical	KR	Yooyoung Pharm Co. Ltd.	09 Aug 2019
Advanced Malignant Solid Neoplasm	Preclinical	KR	Cell Lab MedStartup	13 Jul 2015

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04368507 (ESMO2023) Manual	Phase 1/2	Colorectal Cancer Last line	35	YYB101+ irinotecan	(foesoudexw) = rqbywbktow cpkgjxrnlo (zbkmtwdmgn ) View more	Positive	22 Oct 2023
NCT02499224 (Pubmed \| Ther Adv Med Oncol) Manual	Phase 1	Solid tumor	39	YYB101	(tcdpgetxaz) = zbughwpvri cmlpfgsozi (arwdcqddcc ) View more	Positive	02 Jun 2020
NCT02499224 (ASCO2019)	Phase 1	Solid tumor	39	YYB101	(yavnzslkgp) = athswzjyot epionkeqwj (lzusmwiyrl ) View more	Positive	26 May 2019
NCT02499224 (ASCO2018)	Phase 1	Refractory Malignant Solid Neoplasm	22	YYB101	zgfbgqnljc(uloxixrcej) = anorexia, ALT increase, azotemia were observed at later dose ceydrenlmw (uejunecerd )	Positive	01 Jun 2018