title: First-in-human phase 1 of YS110, a monoclonal antibody directed against CD26 in advanced CD26-expressing cancers.
abstract: BACKGROUND
  YS110 is a humanised IgG1 monoclonal antibody with high affinity to the CD26 antigen. YS110 demonstrated preclinical anti-tumour effects without significant side effects.
  
  
  METHODS
  This FIH study was designed to determine the maximal tolerated dose (MTD) and recommended phase 2 dose (RP2D) to assess the tolerance, pharmacokinetics (PK) and pharmacodynamics profiles of YS110 and preliminary efficacy. YS110 were initially administered intravenously once every 2 weeks (Q2W) for three doses and then, based on PK data, once every week (Q1W) for five doses in patients with CD26-expressing solid tumours.
  
  
  RESULTS
  Thirty-three patients (22 mesothelioma) received a median of 3 (range 1-30) YS110 infusions across six dose levels (0.1-6 mg kg-1). MTD was not reached and two dose-limiting toxicities (infusion hypersensitivity reactions) led to the institution of a systemic premedication. Low-grade asthenia (30.3%), hypersensitivity (27.3%), nausea (15.2%), flushing (15.2%), chills (12.1%) and pyrexia (12.1%) were reported as ADRs. Pharmacokinetic parameters (AUC and Cmax) increased in proportion with the dose. sCD26/DPPIV assays indicated CD26 modulation. Prolonged stable diseases were observed in 13 out of 26 evaluable patients.
  
  
  CONCLUSIONS
  YS110 is well tolerated up to 6 mg kg-1Q1W, which has been defined as the RP2D, with encouraging prolonged disease stabilisations observed in a number of patients with advanced/refractory mesothelioma.
authors.affiliation: Gustave Roussy, Université Paris-Saclay, Drug Development Department (DITEP), Villejuif, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Angevin
authors.affiliation: Centre Georges-François Leclerc, Unité de Phases Précoces, Dijon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Isambert
authors.affiliation: Institut de Cancérologie des Hospices Civils de Lyon, CITOHL, Lyon, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Trillet-Lenoir
authors.affiliation: Institut de Cancérologie des Hospices Civils de Lyon, CITOHL, Lyon, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: You
authors.affiliation: Hôpital Cochin, Paris, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Alexandre
authors.affiliation: Centre Hospitalier Universitaire (CHU) de Caen, Centre de Recherche Clinique/Essais de phases précoces, Caen, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.affiliation: Gustave Roussy, Translational Research Laboratory, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Vielh
authors.affiliation: Gustave Roussy, Translational Research Laboratory, Villejuif, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Farace
authors.affiliation: FV Clinical subcontractor for SynteractHCR SAS, Levallois-Perret, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Valleix
authors.affiliation: Y's therapeutics Inc., Redwood City, CA, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Podoll
authors.affiliation: Kissei Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kuramochi
authors.affiliation: Kissei Pharmaceutical Co., Ltd, Tokyo, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Miyashita
authors.affiliation: Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Hosono
authors.affiliation: Division of Hematology/Oncology, University of Florida, Gainesville, FL, USA.
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Ohnuma
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.|Saitama Medical University, Saitama, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Y's AC Co., Ltd, Tokyo, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D018819:Dipeptidyl Peptidase 4 / Q000097:blood* / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions / Q000097:blood; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; C000621698:YS110 monoclonal antibody; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4