Phase I study of inotuzumab ozogamicin (CMC‐544) in Japanese patients with follicular lymphoma pretreated with rituximab‐based therapy

Abstract

Inotuzumab ozogamicin (CMC‐544), an antibody‐targeted chemotherapeutic agent composed of an anti‐CD22 antibody conjugated to calicheamicin, a potent cytotoxic antibiotic, specifically targets the CD22 antigen present in >90% of B‐lymphoid malignancies, rendering it useful for treating patients with B‐cell non‐Hodgkin lymphoma (B‐NHL). This phase I study evaluated the safety, tolerability, efficacy, and pharmacokinetics of inotuzumab ozogamicin in Japanese patients. Eligible patients had relapsed or refractory CD22‐positive B‐NHL without major organ dysfunction. Inotuzumab ozogamicin was administered intravenously once every 28 days (dose escalation: 1.3 and 1.8 mg/m²). All 13 patients had follicular lymphoma, were previously treated with ≥1 rituximab‐alone or rituximab‐containing chemotherapy, and were enrolled into two dose cohorts (1.3 mg/m², three patients; 1.8 mg/m², 10 patients). No patient had dose‐limiting toxicities, and the maximum tolerated dose, previously determined in non‐Japanese patients (1.8 mg/m²), was confirmed. Drug‐related adverse events (AEs) included thrombocytopenia (100%), leukopenia (92%), lymphopenia (85%), neutropenia (85%), elevated AST (85%), anorexia (85%), and nausea (77%). Grade 3/4 drug‐related AEs in ≥15% patients were thrombocytopenia (54%), lymphopenia (31%), neutropenia (31%), and leukopenia (15%). The AUC and C_max of inotuzumab ozogamicin increased dose‐dependently with pharmacokinetic profiles similar to non‐Japanese. Seven patients had complete response (CR, 54%) including unconfirmed CR, four patients had partial response (31%), and two patients had stable disease (15%). The overall response rate was 85% (11/13). Inotuzumab ozogamicin was well tolerated at doses up to 1.8 mg/m² and showed preliminary evidence of activity in relapsed or refractory follicular lymphoma pretreated with rituximab‐containing therapy, warranting further investigations. This trial was registered in ClinicalTrials.gov (NCT00717925). (Cancer Sci 2010)