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.