A phase II trial of voreloxin in women with platinum-resistant ovarian cancer

5559 Background: Voreloxin is a naphthyridine analog that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Clinical activity has been observed in ovarian cancer and AML. Results are reported from a fully enrolled phase II study of 3 dose levels of single agent voreloxin in patients (pts) with 1° or 2° platinum-resistant or refractory ovarian cancer. Methods: Pts may have received ≤ 3 prior platinum regimens plus one additional non-platinum regimen. PS of 0–1 was required. Voreloxin regimens: Cohort A 48 mg/m 2 q3weeks (wk) (N = 65), Cohort B 60 mg/m 2 q4wk (N = 35), and Cohort C 75 mg/m 2 q4wk (N = 35) by short IV infusion. BRCA status is reported by pt consent. Results: Cohort A: 2CRs, 5PRs; ORR 11%; median PFS 82 days (52–98 days 95%CI); Cohort B: 1CR, 3PRs; ORR 11%, median PFS too early to evaluate (TETE); Cohort C - TETE. Cohort A: Febrile neutropenia (FN) incidence was low (8%). Other common G3 or G4 AEs reported (≥ 5%) were fatigue (14%) and nausea (5%). Dose delays or reductions (40%) occurred typically at Cycle 1, largely due to neutropenia. Cohort B: Dose was increased to 60 mg/m 2 and dosing interval was lengthened to 4 wk, maintaining dose intensity (DI) and allowing adequate time for marrow recovery. ANC dosing criterion was changed from ANC ≥ 1,500 to ≥ 1,000. There was a marked decrease in dose delays and reductions (14%) with only 3% incidence of FN. Common G3 or 4 AEs reported (≥ 5%) were fatigue (11%) and nausea (5%). The safety profile supported further dose escalation to 75 mg/m 2 q4wk (Cohort C- DI increased by 25%). Data are TETE. Conclusions: Preliminary data suggest Cohorts A and B have similar safety and efficacy profiles as anticipated based on comparable DI. Fewer dose reductions and delays occurred in Cohort B, due to revised dosing criteria and increased cycle length to 4 wk. Accrual to Cohort C is complete. Efficacy and safety data for all cohorts will be reported. [Table: see text]