Phase I study of BNC105P, carboplatin and gemcitabine in partially platinum-sensitive ovarian cancer patients in first or second relapse (ANZGOG-1103)

Abstract

The primary objective of this study was to determine the recommended dose of the vascular disrupting agent, BNC105P, in combination with gemcitabine and carboplatin in patients with ovarian cancer in first or second relapse with a minimum 4month progression-free interval after last platinum. Patients received carboplatin AUC4 on day 1 in combination with escalating doses of 800 or 1000mg/m2 gemcitabine on days 1 and 8 and escalating doses of 12 or 16mg/m2 BNC105P on days 2 and 9 every 21days for a maximum for six cycles. Maintenance treatment with 16mg/m2 BNC105P treatment continued for a maximum of six additional cycles. Patients were followed for safety and anti-tumor activity. Fifteen patients were enrolled in the study. Adverse events were most commonly of hematological origin. Dose-limiting toxicities (thrombocytopenia and neutropenia) occurred in two patients at the dose level of 800mg/m2 gemcitabine, carboplatin AUC4 and 16mg/m2 BNC105P. No dose-limiting toxicities were observed at a dose level of gemcitabine 1000mg/m2, carboplatin AUC4 and BNC105P 12mg/m2. BNC105P as a single agent was well tolerated at a dose of 16mg/m2 in maintenance treatment. Ten patients (67%) achieved a complete or partial response according to CA125 and/or RECIST response criteria, four of 13 (31%) responded by RECIST alone. The median progression-free survival was 5.9months. We have established that BNC105P 12mg/m2 with gemcitabine 1000mg/m2 and carboplatin AUC4 is the recommended dose level and has an acceptable toxicity profile. Further exploration of BNC105P in the ovarian cancer setting is planned.