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

Cornell University, Итак, New York, United States
Annals of Oncology (Impact Factor: 7.04). 08/2007; 18(7):1216-23. DOI: 10.1093/annonc/mdm114
Source: PubMed


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 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.
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.
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.

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Available from: Arturo Molina, Sep 24, 2015
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    • "This concept is supported by reports of at least two human-macaque chimeric mAbs, galiximab (IDEC-114, anti-CD80) and lumiliximab (IDEC-152, anti-CD23), in which the VH and VL from cynomolgous macaques were fused with human constant regions. In phase I and II clinical studies, no human anti-galiximab or anti-lumiliximab antibodies were detected in humans [34,35]. Finally, if needed, it would be easier to change a small number of amino acids in the framework region of the macaque VH and VL regions to produce complete germline humanization [36]. "
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