A phase I study of recombinant human arginase I (rhArgI) for patients with advanced hepatocellular carcinoma.

e13503 Background: Patients (pts) with advanced hepatocellular carcinoma (HCC) have a poor prognosis. Pre-clinical data suggest that HCC cells are auxotrophic for arginine through the lack of expression of argininosuccinate synthetase. Recombinant human arginase I (rhArgI) is a novel compound which can achieve near total depletion of plasma arginine. A phase Ia/Ib, open-label, dose-escalation study was conducted to determine the safety, pharmacokinetics (PK), pharmacodynamics (PD), and anti-tumor activity of rhArgI in patients with advanced HCC. Methods: Eligibility criteria included unresectable and/or metastatic HCC with at least 1 target lesion, Karnofsky performance status (KPS) 80% or above, Child-Pugh A or B, and adequate organ function. Weekly doses of rhArgI were escalated from 500 U/kg to 3800 U/kg in a 3 + 3 design. Response was measured by computed tomography according to RECIST criteria. Results: 15 patients enrolled at weekly doses of 500 U/kg (3 pts), 1000 (3), 1600 (3), 2500 (6). The median...