Title |
A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia
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Published in |
Journal of Hematology & Oncology, March 2017
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DOI | 10.1186/s13045-017-0427-x |
Pubmed ID | |
Authors |
Saroj Vadhan-Raj, Rafat Abonour, Jonathan W. Goldman, David A. Smith, Christopher A. Slapak, Robert L. Ilaria, Ramon V. Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L. Tuttle, Yiu-Keung Lau, Eric J. Roeland |
Abstract |
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. 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. 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. 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. ClinicalTrial.gov, NCT01340976. |
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Demographic breakdown
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Student > Bachelor | 8 | 12% |
Researcher | 7 | 11% |
Student > Ph. D. Student | 6 | 9% |
Other | 5 | 8% |
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Other | 9 | 14% |
Unknown | 25 | 38% |
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Unspecified | 1 | 2% |
Other | 4 | 6% |
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