A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia

Journal of Hematology & Oncology

David A. Smith¹  Jonathan W. Goldman²  Sophie Callies³  Joanne Cox³  Yiu-Keung Lau³  Robert L. Ilaria³  Ramon V. Tiu³  Jay L. Tuttle³  Xuejing Wang³  Christopher A. Slapak³  Rafat Abonour⁴  Eric J. Roeland⁵  Saroj Vadhan-Raj⁶ 

[1] Compass Oncology;David Geffen School of Medicine at the University of California;Eli Lilly and Company;Indiana University Simon Cancer Center;Moores Cancer Center, University of California;UT M.D. Anderson Cancer Center;

关键词: Hepcidin;    Ferritin;    Iron;    Cancer;    Anemia;   

DOI  :  10.1186/s13045-017-0427-x

来源: DOAJ

【 摘 要 】

Abstract Background Hepcidin plays a central role in iron homeostasis and erythropoiesis. Neutralizing hepcidin with a monoclonal antibody (mAb) may prevent ferroportin internalization, restore iron efflux from cells, and allow transferrin-mediated iron transport to the bone marrow. This multicenter, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of a fully humanized mAb (LY2787106) with high affinity for hepcidin in cancer patients with anemia. Methods Thirty-three patients with hepcidin levels ≥5 ng/mL received LY2787106 either every 3 weeks (19 patients, dose range 0.3–10 mg/kg) (part A) or weekly (14 patients, dose 10 mg/kg) (part B). LY2787106 PK/PD markers of iron and hematology biology were measured. Results LY2787106 clearance (32 mL/h) and volume of distribution (7.7 L) were independent of dose and time, leading to a dose-proportional increase in concentration with dose. Consistent dose-dependent increases in serum iron, and transferrin saturation were seen at the 3 and 10 mg/kg dose levels, typically peaking within 24 h after LY2787106 administration and returning to baseline by day 8. Conclusions Our findings indicate that LY2787106 was well tolerated in cancer patients with anemia and that targeting the hepcidin-ferroportin pathway by neutralizing hepcidin resulted in transient iron mobilization, thus supporting the role of hepcidin in iron regulation. Trial registration ClinicalTrial.gov, NCT01340976

【 授权许可】

Unknown