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01-01-2019 | Original Article

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

Authors: Kristina Lindemann, Philip J. Beale, Emma Rossi, Jeff C. Goh, Michelle M. Vaughan, Meaghan E. Tenney, Julie K. Martyn, Dirkje Sommeijer, Jose L. Iglesias, Gabriel Kremmidiotis, Jeremy Simpson, Elizabeth Doolin, Tina C. Lavranos, Annabell Leske, Anneso S. Veillard, David Espinoza, Martin R. Stockler, Danny Rischin, For ANZGOG and HCRN Collaborative Groups

Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2019

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Title: Phase I study of BNC105P, carboplatin and gemcitabine in partially platinum-sensitive ovarian cancer patients in first or second relapse (ANZGOG-1103)
Authors: Kristina Lindemann
Philip J. Beale
Emma Rossi
Jeff C. Goh
Michelle M. Vaughan
Meaghan E. Tenney
Julie K. Martyn
Dirkje Sommeijer
Jose L. Iglesias
Gabriel Kremmidiotis
Jeremy Simpson
Elizabeth Doolin
Tina C. Lavranos
Annabell Leske
Anneso S. Veillard
David Espinoza
Martin R. Stockler
Danny Rischin
For ANZGOG and HCRN Collaborative Groups
Publication date: 01-01-2019
Publisher: Springer Berlin Heidelberg
Published in: Cancer Chemotherapy and Pharmacology / Issue 1/2019
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-018-3706-5

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