Phase I study of BCX 1777 (forodesine) in patients with relapsed or refractory peripheral T /natural killer‐cell malignancies

BCX 1777 (forodesine), a novel purine nucleoside phosphorylase inhibitor, induces apoptosis, mainly in T cells. To evaluate the safety, tolerability, and pharmacokinetics of BCX 1777, we conducted a phase I study in patients with relapsed or refractory peripheral T /natural killer‐cell malignancies. Eligible patients had relapsed or refractory peripheral T /natural killer‐cell malignancies without any major organ dysfunction. BCX 1777 was administered orally once daily (dose escalation: 100, 200, and 300 mg) until disease progression requiring new therapy or unacceptable adverse events occurred. A total of 13 patients were enrolled and treated in three dose cohorts (100 mg/day, five patients; 200 mg/day, three patients; 300 mg/day, five patients). Although none of the patients developed dose‐limiting toxicities, further dose escalation was not performed based on data from overseas. Therefore, the maximum tolerated dose was not determined. Adverse events of grade 3 or greater (≥2 patients) included lymphopenia (62%), anemia (15%), leukopenia (8%), and pyrexia (8%). Plasma pharmacokinetics parameter of BCX 1777 (area under the plasma concentration‐time curve) at day 1 in each cohort was 1948 ± 884, 4608 ± 1030, and 4596 ± 939 ng•h/mL, respectively. Disease control was achieved in approximately half of patients. One patient with anaplastic large cell lymphoma, which was negative for anaplastic lymphoma kinase, achieved a complete response, and two patients with cutaneous T ‐cell lymphoma achieved partial responses. BCX 1777 was well tolerated at doses up to 300 mg once daily and showed preliminary evidence of activity in relapsed or refractory peripheral T /natural killer‐cell malignancies, warranting further investigation. ( Cancer Sci 2012; 103: 1290–1295)