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SB-743921, our second KSP inhibitor to enter clinical trials, is structurally distinct from ispinesib, Cytokinetics' most advanced anti-cancer drug candidate. SB-743921 was the subject of a Phase I/II clinical trial in Hodgkin and non-Hodgkin Lymphoma that has been completed Development Status of SB-743921Phase I/II Clinical Trial in Hodgkin and non-Hodgkin Lymphoma Details At the 2009 Annual Meeting of the American Society of Hematology, we presented data summarizing the Phase I portion of a multi-center, international Phase I/II open-label, non-randomized dose-finding clinical trial evaluating SB-743921 in patients with non-Hodgkin or Hodgkin Lymphoma who have progressed or relapsed on standard therapy. The primary objectives of this clinical trial were to determine the dose-limiting toxicities (DLTs) and the maximum-tolerated dose (MTD) of SB-743921 administered as a 1-hour infusion on days 1 and 15 of a 28-day cycle, first without and then with prophylactic granulopoietic factor support (i.e., granulocyte colony-stimulating factor or G-CSF) and to assess the safety and tolerability of SB-743921 on this schedule. The secondary objectives were to characterize the pharmacokinetics of SB-743921 administered on this schedule and to evaluate the effect of SB-743921 on biomarkers of cell proliferation in patients with accessible tumors. Phase I Details At the American Society of Clinical Oncology (ASCO) annual meeting in May 2006, data was presented from an open-label, non-randomized, dose-finding, first-in-humans Phase I clinical trial of SB-743921in patients with advanced solid tumors. The authors concluded that SB-743921 appeared to have an acceptable tolerability profile on a once-every-21-day schedule. The MTD in the first-in-humans trial was 4 mg/m2 every 21 days, although dosing reached 8 mg/m2. The DLTs reported at that time were prolonged neutropenia, febrile neutropenia (with or without infection), elevated transaminases, hyperbilirubinemia and hyponatremia. Neurotoxicities, mucositis, thrombocytopenia, alopecia and nausea/vomiting requiring pre-medication were not observed. |