A phase II clinical trial of the Vascular Disrupting Agent BNC105P as second line chemotherapy for advanced Malignant Pleural Mesothelioma
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- 作者：Anna K. Nowak ; Chris Brown ; Michael J. Millward ; Jenette Creaney ; Michael J. Byrne ; Brett Hughes ; Gabriel Kremmidiotis ; David C. Bibby ; Annabell F. Leske ; Paul L.R. Mitchell ; Nick Pavlakis ; Michael Boyer ; Martin R. Stockler
- 关键词：Mesothelioma ; Vascular Disrupting Agent ; BNC105P ; Clinical trial ; Phase II ; Biomarkers
- 刊名：Lung Cancer
- 出版年：2013
- 出版时间：September, 2013
- 年：2013
- 卷：81
- 期：3
- 页码：422-427
- 全文大小：631 K
文摘
BNC105P is a tubulin polymerisation inhibitor that selectively disrupts tumour vasculature and suppresses cancer cell proliferation. This agent has exhibited preclinical and phase I activity in Malignant Pleural Mesothelioma (MPM). This phase II, single arm trial investigated the efficacy and safety of BNC105P as second line therapy in MPM. Participants had progressive MPM after first line pemetrexed/platinum chemotherapy, ECOG PS 0-1, adequate organ function, and measurable disease. BNC105P 16 mg/m2 was administered intravenously on day 1 and 8 every 21 days until progression or undue toxicity. The primary endpoint was centrally reviewed objective response rate (RR). Tumour response was assessed every two cycles using modified RECIST. 30 patients were enrolled in 10 months, predominantly male (90 % ), ECOG PS 1 (77 % ), epithelioid histology (67 % ), and non-metastatic disease (67 % ). All patients received at least one dose of study drug, with a median of 2 cycles. No significant haematologic, biochemical, or cardiac adverse events (AEs) were observed. Grade 3 or 4 AEs occurred in 10 patients (33 % ). There were 2 deaths on study: 1 cardiorespiratory, the other to pneumonia. We observed 1 partial response (3 % ); 13 patients had stable disease (43 % ). Median progression free survival was 1.5 months (95 % CI 1.4-2.4); median overall survival was 8.2 months (95 % CI 3.8-11.9). BNC105P was safe and tolerable. The sole response was insufficient to warrant further research as a single agent.