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Background: CP-4055 (cytarabine 5’-elaidic acid ester) is a cytotoxic nucleoside analog with broad preclinical antitumor activity in solid tumors and hematologic malignancies. Lipid Vector Technology (LVT) is used to make CP-4055 which confers a different cellular uptake profile to cytarabine with a similar mechanism of action. A phase I study in solid tumors determined a recommended Phase II dose of 200 mg/m²/day in a day 1-5 q4 weeks (q4w) schedule and showed clinical activity (Aamdal et al., AACR 2005). The dose limiting toxicity (DLT) was neutropenia. A phase I /II study with PK assessment is being conducted in patients (pts) with refractory leukemias.

Methods: Pts received IV CP-4055 over 2 hours (Arm A) or 24 hours (CIV, Arm B) in a day 1-5 q3w schedule. The dose is escalated by a factor of 1.5 in both treatment arms. The starting dose in Arm A was 300 mg/m²/day and in Arm B 200 mg/m²/day, with standard definitions of DLT for hematologic malignancies.

Results: In the ongoing study, 11 pts [10 male, median age 69 (range 54-77); ECOG PS 0-1: 9 pts, ECOG PS 2: 2 pts; AML 10 pts, MDS 1 pt; mean 2.5 lines prior chemotherapy (range 1-4)] have been treated in US and European centers; 4 pts are still ongoing, 4 pts were withdrawn with minimal response and 3 pts discontinued due to progressive disease. No treatment-related serious adverse events (SAE) have been observed. As no DLT has been observed, dose escalation is ongoing at doses 675 mg/m²/day in Arm A and at 300 mg/m²/day in Arm B. Nausea and vomiting were the only possibly related grade 1/2 AEs observed. Efficacy: 5 pts received 2 cycles of therapy, 2 pts had stable disease/mild myelosuppression and received a third cycle with CP-4055; one is ongoing.

Conclusions: CP-4055 is well tolerated by patients with hematologic malignancies up to a dose of 675 mg/m²/day in a q3w schedule and accrual is ongoing. Updated results, including PK, will be presented.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA