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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Hematology & Oncology 1/2017

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

Zeitschrift:
Journal of Hematology & Oncology > Ausgabe 1/2017
Autoren:
Saroj Vadhan-Raj, Rafat Abonour, Jonathan W. Goldman, David A. Smith, Christopher A. Slapak, Robert L. Ilaria Jr, Ramon V. Tiu, Xuejing Wang, Sophie Callies, Joanne Cox, Jay L. Tuttle, Yiu-Keung Lau, Eric J. Roeland
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13045-017-0427-x) contains supplementary material, which is available to authorized users.
Presented in abstract form as an oral presentation at the 57th annual meeting of the American Society of Hematology, Orlando, FL, 7 December 2015.

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

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Zusatzmaterial
Additional file 1: Inclusion Criteria. Exclusion Criteria. Stopping Rules. Figure S1. Changes in (A) serum iron and (B) transferrin saturation from baseline in 3- and 10-mg/kg dosing cohorts in part A, as determined at interim analysis before start of part B. (DOCX 336 kb)
13045_2017_427_MOESM1_ESM.docx
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