Phase I study of BNC105P, carboplatin and gemcitabine in partially platinum-sensitive ovarian cancer patients in first or second relapse (ANZGOG-1103)
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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 4 month progression-free interval after last platinum.
Patients received carboplatin AUC4 on day 1 in combination with escalating doses of 800 or 1000 mg/m2 gemcitabine on days 1 and 8 and escalating doses of 12 or 16 mg/m2 BNC105P on days 2 and 9 every 21 days for a maximum for six cycles. Maintenance treatment with 16 mg/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 800 mg/m2 gemcitabine, carboplatin AUC4 and 16 mg/m2 BNC105P. No dose-limiting toxicities were observed at a dose level of gemcitabine 1000 mg/m2, carboplatin AUC4 and BNC105P 12 mg/m2. BNC105P as a single agent was well tolerated at a dose of 16 mg/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 5.9 months.
We have established that BNC105P 12 mg/m2 with gemcitabine 1000 mg/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.
KeywordsBNC105P Vascular disrupting agent (VDA) Ovarian cancer Phase I Gemcitabine Carboplatin
We thank Dave Cannon, NHMRC Clinical Trials Centre, for the administrative support during drafting and submission of the manuscript.
This trial was conducted by ANZGOG and HCRN with funding provided by Bionomics.
Compliance with ethical standards
Conflict of interest
Dr. Lindemann, Dr. Veillard, Dr. Espinoza. Dr. Sommeijer, Dr. Rossi, Dr. Simpson, Dr. Tenney, Dr. Goh and Dr. Vaughan declare that they have nothing to disclose. Dr. Lavranos, Ms. Doolin, Ms. Leske and Dr. Kremmidiotis report salary/stakeholder from Bionomics Limited, outside the submitted work. Dr. Iglesias reports salary from Bionomics Limited, outside the submitted work and has a patent on BNC105 pending. Dr. Martyn reports Grants and non-financial support from Bionomics, during the conduct of the study. Dr. Beale reports personal fees from Roche, personal fees from Astra Zeneca, Grants from Roche, outside the submitted work. Dr. Rischin reports a Grant from Bionomics to ANZGOG for the research costs of the study; in addition, Dr. Rischin has a patent B55 (US) BNC105 Triple Combination Patent Application pending and trial steering/scientific advisory committees—Bionomics, Merck, Amgen, Regeneron, Bristol-Myers—all uncompensated. Dr. Stockler reports Grants from Bionomics, during the conduct of the study; Grants from Bayer, Grants from BMS, Grants from Astra Zeneca, Grants from Specialised Therapeutics, Grants from Amgen, Grants from Astellas, Grants from Merck, outside the submitted work.
All procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments.
Informed consent was obtained from all individual participants included in the study.
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