Phase I / II study of brentuximab vedotin in J apanese patients with relapsed or refractory CD 30‐positive H odgkin's lymphoma or systemic anaplastic large‐cell lymphoma

Brentuximab vedotin is an antibody–drug conjugate that selectively delivers the antimicrotubule agent monomethyl auristatin E into CD 30‐expressing cells. To assess its safety, pharmacokinetics, and efficacy in Japanese patients with refractory or relapsed CD 30‐positive H odgkin's lymphoma or systemic anaplastic large‐cell lymphoma, we carried out a phase I/ II study. Brentuximab vedotin was given i.v. on day 1 of each 21‐day cycle up to 16 cycles. In the phase I part of a dose‐escalation design, three patients per cohort were treated at doses of 1.2 and 1.8 mg/kg. In the phase  II part, a dose of 1.8 mg/kg was given to 14 patients (nine with Hodgkin's lymphoma and five with systemic anaplastic large‐cell lymphoma). The median number of treatment cycles was 16 (range, 4–16). In the phase I part, no dose‐limiting toxicity event was observed. In the total population, common adverse events included lymphopenia (80%), neutropenia (65%), leukopenia (65%), and peripheral sensory neuropathy (60%). Grade 3/4 adverse events in more than two patients were lymphopenia (50%) and neutropenia (15%). The pharmacokinetic profile was similar to that observed in the previous studies in the USA. In the phase II part, six patients (67%) with H odgkin's lymphoma achieved an objective response with 56% of complete response rate, and five patients (100%) with systemic anaplastic large‐cell lymphoma achieved an objective response with 80% of complete response rate. These results show that brentuximab vedotin has an acceptable safety profile and promising antitumor activity in the J apanese population. This trial was registered in JAPIC C linical T rials I nformation ( J apic CTI ‐111650).