A phase I/II dose-escalation trial of EPO906 every 3 weeks in patients with relapsed/refractory ovarian, primary fallopian, or primary peritoneal cancer

Abstract

5102 Background: Patients (pts) with newly diagnosed advanced ovarian cancer generally receive a taxane in combination with a platinum agent. However, pts refractory to this therapy have few treatment options. Taxane efficacy can be limited by the development of drug-resistance mechanisms, and taxanes are associated with neutropenia and neuropathies. EPO906 is a potent microtubule stabilizer that has demonstrated clinical cytotoxic activity in taxane-sensitive, -resistant, and -refractory tumors. In a phase I/II study, we investigated the safety and efficacy of EPO906 in pts with advanced ovarian, primary fallopian, or primary peritoneal cancer who had failed to respond to or had relapsed within 6 months of first-line taxane plus platinum therapy. Methods: During phase I, dose escalation followed the standard 3 + 3 design until the MTD was reached. Pts received EPO906 at a starting dose of 6.5 mg/m2 via 5-min IV infusion once every 3 wks with aggressive diarrhea management at first sign of abdominal cramping. During phase II, pts will be treated at the MTD for 6 cycles or until disease progression. Results: To date, 6 pts have been enrolled in 2 cohorts receiving 6.5 mg/m2 (n = 3) or 7.0 mg/m2 (n = 3) EPO906. Median age was 56 yrs (range, 33 - 69 yrs). Before study entry, these pts had received a median of 6 cycles of carboplatin plus paclitaxel. Pts have received a median of 3 cycles (range, 2 - 6 cycles) of EPO906. No DLTs have been reported; thus, the MTD has not been reached. Grade 3 AEs—vomiting (n = 2), diarrhea (n = 1), and dehydration (n = 1)—were observed in cycle 2 and thus were not DLT. Grade ≤ 2 diarrhea (n = 2) and nausea (n = 1) were also reported. No pts experienced hematologic or peripheral neurologic toxicity. Radiologic tumor assessment shows 2 pts with SD (1 at 4 cycles; 1 at 6 cycles). Conclusion: Preliminary data indicate that EPO906 administered once every 3 wks is safe and well tolerated in this population. MTD has not been reached and dose escalation continues. Phase II portion of this study will assess the clinical activity of EPO906 in the treatment of advanced ovarian, primary fallopian, or primary peritoneal cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharma AG Novartis Pharma AG Novartis Pharma AG Novartis Pharma AG; Novartis Pharmaceuticals, Inc. Novartis Pharmaceuticals, Inc.