498P - First-In-Human Phase I Administration of YS110, A Humanized Monoclonal Antibody Directed Against the CD26 Molecule in Cancer Patients

Abstract

ABSTRACT Background YS110 is a recombinant humanized IgG1 monoclonal antibody that selectively binds with high affinity to the extracellular domain of the CD26 antigen. CD26, a widely distributed 110-kDa transmembrane glycoprotein with intrinsic DPPIV activity and its truncated soluble form (sCD26/DPPIV) also present in serum and fluids, is known to play an important role in tumor biology. CD26 is frequently highly expressed on multiple cancer cell types, especially mesothelioma and renal cell carcinoma (RCC). In addition to its role in proteolysis via the DPPIV activity, CD26 also acts as a receptor involved in T-cell co-stimulation and immune regulation. Preclinical evaluations of YS110 have demonstrated anti-tumor effects in cancer cell lines and xenografts expressing the CD26 antigen without significant side effects in toxicology studies (up to 100 mg/kg as single dose or 30 mg/kg for 5 weekly doses in cynomolgus monkeys). Phase I design and endpoints The ongoing YSCMA-EU-0001 trial is a Phase I/II study of YS110 escalating dose administered intravenously once every 2 weeks for 3 doses (Days 1, 15, 29). Patients must have progressive locally advanced inoperable and/or metastatic histologically confirmed solid tumors, refractory to prior standard therapies, with confirmed CD26+ tumor expression (≥ 20% of the tumor cells by central IHC evaluation). The primary endpoint is to determine the Maximum Tolerated Dose/Recommended Dose of YS110 and the pattern of DLTs. Secondary endpoints are the determination of the PK/PD parameters (i.e. analysis of cytokine release, immunophenotyping, circulating DPPIV activity and sCD26 antigen level). Preliminary antitumor efficacy is evaluated by RECIST1.1 criteria at Day 43. Patients demonstrating objective response or stable disease receive additional treatment cycles. Status of the study As of May 1st 2012, 22 patients (13 mesothelioma, 9 RCC) have been treated with 3 bi-weekly infusions over 29 days at 0.1, 0.4, 1 and 2 mg/kg. Based on PK data for them, the next cohort of 3 patients will be dosed at 2 mg/kg with weekly infusions over 29 days starting in May 2012. Safety, PK/PD, and preliminary efficacy data will be presented. Disclosure T. Podoll: Compensated employment position : President of Y\\'s Therapeutics Compensated Consultant role. I. Miyashita: Compensated Employment role: Director Kissei Pharmaceuticals Co, Ltd. Y. Kaneko: Compensated employment role : managing board of directors Y's AC Stock ownership: Y's AC. C. Morimoto: Compensated Consultant role : Kissei Pharmaceuticals Co, Ltd Stock ownership: Y's Therapeutics Honororia: Kissei Pharmaceuticals Co, Ltd Research funding: Y's Therapeutics. All other authors have declared no conflicts of interest.