An oral methionine aminopeptidase II inhibitor for high-risk non-muscle invasive bladder cancer relapsed after intravesical therapies: Update of a phase II trial.

作者：Dingwei, Ye; Xudong, Yao; Gongxian, Wang; Jinxian, Pu; Xin, Yao; Fangjian, Zhou; Jun, Qi; Zhangqun, Ye; Liping, Xie; Jimin, Chen; Keji, Xie; Xiaokun, Zhao; Zhihui, Xu; Hongqian, Guo; Yong, Yang; Dalong, Cao; Bin, Yang; Cheng, Zhang; Yong, Lu; Jun, Du

来源：Journal of Clinical Oncology, 2017, 35(6_suppl): 303-303.

DOI：10.1200/jco.2017.35.6_suppl.303

<jats:p> 303 </jats:p><jats:p> Background: In 2016, we reported the preliminary results of APL-1202, an oral MetAP2 inhibitor, in the first 18 patients enrolled in the phase II trial. The purpose of the present study is to update the results of efficacy, safety, pharmacokinetics at steady state and translational studies in 41 patients. Methods: This is an open-label, single-arm phase II trial conducted in 15 hospitals in China. High-risk in recurrence is defined according to EORTC recurrence score and probability tables in EAU 2012 Guidelines on NMIBC. The primary end point is the recurrence-free survival rate at 1 year. Plasma and urine samples at steady state were collected for pharmacokinetic studies, and separate plasma samples were collected for translational studies. Results: From May 2014, a total of 41 patients have been enrolled in this study, including 39 relapsed after intravesical chemotherapies only (chemo-failed subgroup), and 2 after both chemo and BCG treatments (BCG-failed subgroup). All of patients had TaT1 papillary tumors, and 3 with concurrent carcinoma in situ . APL-1202 did not cause any drug-related SAEs. By the time of this abstract submission, the 1-year recurrence-free rate is 54.3% (37.2-73.2%, 95% Confidence Interval) with a median recurrence-free survival of 14.7 months. APL-1202’s plasma exposure at steady state appears to increase proportionally to the increase of doses. Conclusions: APL-1202 is safe and well tolerated at a daily dose up to 750mg, TID, for 12 weeks followed by 3 months on-and-off in patients with recurred high-risk NMIBC. According to the EAU 2012 Guidelines on NMIBC, naïve high-risk NMIBC patients treated by intravesical chemotherapies have a 1-year recurrence-free rate of 39% (33-45%, 95% CI) with a median recurrence-free survival of 9 months. Our results support the concept that oral MetAP2 inhibitor APL-1202 as a second-line therapy has the potential to achieve at least similar efficacy with the first-line intravesical chemotherapies, and warrant a randomized trial alone or in combination with other therapies in NMIBC patients. Clinical trial information: CTR20131716. </jats:p>

• 出版日期2017-2-20
• 单位中山大学; 上海交通大学; 复旦大学; 浙江大学; 同济大学; 南京大学; 天津医科大学; 中南大学