1, 2 In contrast with naked antibodies, an ideal ADC target should be internalized to allow delivery of the cytotoxic drug inside the tumor cells. The pharmacokinetic profile of SAR3419 is characterized by linear kinetics, low clearance from 0.2 to 0.6 L/d/m 2, and an elimination half-life in the range of 3 to 7 days.Īntibody–drug conjugates (ADCs) provide an opportunity to selectively deliver cytotoxic therapy to cancer cells and, therefore, can improve the therapeutic efficacy of the naked antibody while decreasing the toxicity of systemically administered cytotoxic therapy. Seven (47%) of 15 patients with rituximab-refractory disease demonstrated reduction in their tumor sizes. Twenty-six patients (74%) demonstrated reduction in their tumor size six of those patients achieved partial or complete remissions.
A total of 35 patients have completed at least two cycles of treatment and were evaluable for tumor response. Hematologic and hepatic toxicities were predominantly grade 1 or 2 in severity. The MTD was 160 mg/m 2 once every 21 days.
The dose-limiting toxicities were reversible severe blurred vision associated with microcystic epithelial corneal changes reported in six patients and neuropathy in one patient. The median number of prior treatment regimens was four (range, 1 to 9), and 11 patients had prior autologous or allogeneic stem-cell transplantation. Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m 2.
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