A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma.

BACKGROUND: Galiximab is a monoclonal antibody that targets CD80, a costimulatory molecule constitutively expressed on follicular and other lymphomas. Modest single-agent clinical activity and tolerability were demonstrated in a phase I study in relapsed or refractory, follicular non-Hodgkin's lymphoma (NHL). A phase I/II study was conducted to evaluate galiximab in combination with a standard course of rituximab. Safety, pharmacokinetics, and efficacy were evaluated. PATIENTS AND METHODS: Patients with follicular NHL who had relapsed or failed primary therapy were enrolled. Rituximab-refractory patients (no response or a response with time to progression <6 months) were excluded. Patients received 4 weekly i.v. infusions of galiximab (125, 250, 375, or 500 mg/m(2)) and rituximab (375 mg/m(2)). International Workshop Response Criteria (IWRC) were used to evaluate response. RESULTS: Seventy-three patients received treatment. All had received at least one prior lymphoma therapy; 40% were rituximab naive. Infusions were delivered in an outpatient setting and were well tolerated. The most common study-related adverse events (AE) were lymphopenia, leukopenia, neutropenia, fatigue, and chills. The overall response rate at the recommended phase II dose of galiximab (500 mg/m(2)) was 66%: 19% complete response, 14% unconfirmed complete response, and 33% partial response. The median progression free survival was 12.1 months. Combination therapy did not appear to alter pharmacokinetics. CONCLUSION: These results indicate that galiximab can be safely combined with a standard course of rituximab. This doublet biologic approach offers the potential to avoid or delay chemotherapy or to integrate with other lymphoma therapies. A phase III, randomized study evaluating clinical benefit of rituximab versus the combination has been initiated.