A phase II study of YM155, a novel survivin suppressant, administered by 168 hour continuous infusion in patients with unresectable stage III or stage IV melanoma

8538 Background: In cell line studies, YM155 showed markedly potent antiproliferative activity against melanoma with 50% growth inhibition (GI50) values ranging from 0.35 nM to 910 nM. In melanoma tumor-bearing mouse xenograft models, YM155 showed significant antitumor activity including regression of tumors, at doses ranging from 1 to 10 mg/kg/day. Methods: Chemotherapy naive patients with unresectable Stage III or IV melanoma were eligible. The primary endpoint was tumor response defined by RECIST criteria. Secondary endpoints included progression-free survival and toxicity. A Simon's two stage minimax design was utilized with the first stage requiring 1 response (N=27) and a total of 2 responses required at the conclusion of stage II (N=29). Patients were considered evaluable if they completed 2 cycles. YM155 was given as a 168-hour (7-day) continuous infusion every three weeks (1 cycle) at a dose of 4.8 mg/m2/day. Results: Enrollment is complete at 34 pts in order to reach 29 evaluable with treatment ...