Phase I/II randomised study of a novel erythropoiesis-stimulating agent (AMG 114) for the treatment of anaemia with concomitant chemotherapy in patients with non-myeloid malignancies.
AMG 114 is a novel, hyperglycosylated erythropoiesis-stimulating agent. In preclinical studies, AMG 114 demonstrated increased potency and longer half-life than darbepoetin alfa and epoetin alfa. This phase I/II, randomised, double-blind, placebo-controlled, dose-escalation study evaluated safety, pharmacokinetics, and efficacy of AMG 114 in patients with non-myeloid malignancies and chemotherapy-induced anaemia. Patients were randomised (1:5) to receive subcutaneous placebo or AMG 114 Q3W for 6 weeks in 3 dose cohorts of 15 μg (cohort A1), 50 μg (cohort A2), or 200 μg (cohort A3). Safety endpoints included incidence of adverse events and dose-limiting toxicities (DLTs). The PK profile of AMG 114 was evaluated. Efficacy was assessed by change in haemoglobin from baseline to end of treatment. Forty-eight patients enrolled: 8 received placebo, 40 received AMG 114. No DLTs were observed; adverse events were consistent with underlying malignancies. The PK profile was dose-proportional over the dose range tested; terminal half-life of AMG 114 was approximately 130 h. Mean change (range) in haemoglobin from baseline in AMG 114-treated patients was -0.16 (-1.8 to 1.3), 0.21 (-1.5 to 3.4), and 0.76 (-1.0 to 2.9) g/dl in cohorts A1, A2, and A3, respectively. AMG 114 appeared to be well tolerated, but the study was halted, in part because of modest efficacy.
Department of Medical Oncology, Royal Melbourne Hospital, Grattan St., Parkville, 3050, Australia. richard.deboer@wh.org.au
Richard
R
de Boer
Michael
M
Clemens
Gabor
G
Renczes
Dusan
D
Kotasek
Jana
J
Prausova
Norbert
N
Marschner
Michael
M
Hedenus
Sameer
S
Doshi
Lisa
L
Hendricks
Anders C
AC
Österborg
D000740:Anemia / Q000139:chemically induced / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D006454:Hemoglobins / Q000187:drug effects*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology
D000970:Antineoplastic Agents; D006397:Hematinics; D006454:Hemoglobins