SB-743921, our second KSP inhibitor to enter clinical trials, is structurally distinct from ispinesib, Cytokinetics' most advanced anti-cancer drug candidate. SB-743921 arose from our joint research activities conducted in collaboration with GlaxoSmithKline that initially focused on the area of KSP inhibition.
SB-743921 is currently the subject of a Phase I/II clinical trial in Hodgkin and non-Hodgkin Lymphoma.
Development Status of SB-743921
Ongoing Clinical Trials Details
Under an amendment to our collaboration and license agreement with GSK, we assumed responsibility for the costs and activities associated with the continued development of the KSP inhibitors ispinesib and SB-743921, subject to GSK’s option to resume responsibility for some or all development and commercialization activities associated with each of these novel drug candidates. In April 2006, in connection with its expanded development program for SB-743921, Cytokinetics announced the initiation of its Phase I/II clinical trial of SB-743921 in patients with Non-Hodgkin and Hodgkin lymphoma.
At the 2007 Annual Meeting of the American Society of Hematology, we presented interim data on the Phase I/II clinical trial of SB-743921 in patients with NHL and Hodgkin’s lymphoma. In that interim analysis, SB-743921 was considered well-tolerated without prophylactic GCSF in doses less than 6 mg/m2 when given on days 1 and 15 of a 28-day schedule. At that time, the best response observed was a partial response in a patient with Hodgkin lymphoma out of 23 patients evaluable for efficacy. In this interim analysis, grade 3 or 4 neutropenia was the most common toxicity reported and grade 3 or 4 non-hematological toxicities were rare. In particular, there has been no evidence of neuropathy. To fully address the identification of the DLT and the MTD in the absence of primary GCSF support, the 6 mg/m2 cohort will be expanded to include up to six additional evaluable patients prior to a final decision on further dose escalation beyond 7 mg/m2 without primary GCSF prophylactic support. Efficacy signals in both non-Hodgkin and Hodgkin lymphoma will be explored in Phase II once the MTDs, one with and one without primary GCSF prophylaxis, are determined.
Phase I Details
At the American Society of Clinical Oncology (ASCO) annual meeting in May 2006, GlaxoSmithKline (GSK) presented data 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.
