TY - JOUR
T1 - First-in-human phase 1 of YS110, a monoclonal antibody directed against CD26 in advanced CD26-expressing cancers
AU - Angevin, Eric
AU - Isambert, Nicolas
AU - Trillet-Lenoir, Véronique
AU - You, Benoit
AU - Alexandre, Jérôme
AU - Zalcman, Gérard
AU - Vielh, Philippe
AU - Farace, Françoise
AU - Valleix, Fanny
AU - Podoll, Thomas
AU - Kuramochi, Yu
AU - Miyashita, Itaru
AU - Hosono, Osamu
AU - Dang, Nam H.
AU - Ohnuma, Kei
AU - Yamada, Taketo
AU - Kaneko, Yutaro
AU - Morimoto, Chikao
PY - 2017/4/25
Y1 - 2017/4/25
N2 - 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 C max) 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-1 Q1W, which has been defined as the RP2D, with encouraging prolonged disease stabilisations observed in a number of patients with advanced/refractory mesothelioma.
AB - 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 C max) 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-1 Q1W, which has been defined as the RP2D, with encouraging prolonged disease stabilisations observed in a number of patients with advanced/refractory mesothelioma.
UR - http://www.scopus.com/inward/record.url?scp=85015164255&partnerID=8YFLogxK
U2 - 10.1038/bjc.2017.62
DO - 10.1038/bjc.2017.62
M3 - Article
C2 - 28291776
AN - SCOPUS:85015164255
SN - 0007-0920
VL - 116
SP - 1126
EP - 1134
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 9
ER -