A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia.
J Hematol Oncol
; 10(1): 73, 2017 03 21.
Article
in En
| MEDLINE
| ID: mdl-28327200
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antibodies, Monoclonal, Humanized
/
Hepcidins
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Anemia
/
Neoplasms
Type of study:
Clinical_trials
/
Etiology_studies
/
Risk_factors_studies
Limits:
Adult
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Aged
/
Aged80
/
Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
J Hematol Oncol
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
Year:
2017
Document type:
Article
Affiliation country: