Cancer Institute A national cancer institute
designated cancer center

Kristen N Ganjoo

Publication Details

  • Results of a Phase 1 Study of AME-133v (LY2469298), an Fc-Engineered Humanized Monoclonal Anti-CD20 Antibody, in Fc gamma RIIIa-Genotyped Patients with Previously Treated Follicular Lymphoma CLINICAL CANCER RESEARCH Forero-Torres, A., de Vos, S., Pohlman, B. L., Pashkevich, M., Cronier, D. M., Dang, N. H., Carpenter, S. P., Allan, B. W., Nelson, J. G., Slapak, C. A., Smith, M. R., Link, B. K., Wooldridge, J. E., Ganjoo, K. N. 2012; 18 (5): 1395-1403

    Abstract:

    AME-133v is a humanized monoclonal antibody engineered to have increased affinity to CD20 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) better than rituximab. Safety, pharmacokinetics, and efficacy were assessed in a phase 1/2 trial in patients with previously treated follicular lymphoma (FL).AME-133v was characterized in vitro by ADCC and cell binding assays. A phase 1 study was conducted in which 23 previously treated patients with FL were assigned sequentially to one of five dose-escalation cohorts of AME-133v at 2, 7.5, 30, 100, or 375 mg/m(2) weekly × 4 doses.AME-133v showed a 13- to 20-fold greater binding affinity for CD20 and was 5- to 7-fold more potent than rituximab in ADCC assays. Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, and AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner. AME-133v was well tolerated by patients and common related adverse events included chills and fatigue. One patient experienced a dose-limiting toxicity of neutropenia. AME-133v showed nonlinear pharmocokinetics with properties similar to rituximab. Selective reduction of B cells during and after AME-133v treatment was shown by flow cytometry of peripheral blood. A partial or complete response was observed in 5 of 23 (22%) patients and the median progression-free survival was 25.4 weeks.AME-133v was safe and well tolerated at the doses tested. AME-133v showed encouraging results as an anti-CD20 therapy in heavily pretreated FL patients with the less favorable Fc?RIIIa F-carrier genotype.

    View details for DOI 10.1158/1078-0432.CCR-11-0850

    View details for Web of Science ID 000301040700023

    View details for PubMedID 22223529

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