2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
A phase I study to evaluate safety, tolerability, pharmacokinetics and antineoplastic activity of BPI-7711 in patients with EGFR/T790M mutation advanced or recurrent NSCLC.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #357)
J Clin Oncol 37, 2019 (suppl; abstr 9034)
Author(s): Yuankai Shi, Jian Fang, Yongqian Shu, Donglin Wang, Huiqing Yu, Yanqiu Zhao, Liangming Zhang, Bo Zhu, Xingya Li, Gongyan Chen, Jianhua Shi, Rongsheng Zheng, Jian'An Huang, Sheng Yang, Jieran Long, Wen Gao, Michael Greco, Jing Wang, Xiao Li; Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China; Beijing Cancer Hospital, Beijing, China; Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China; Chongqing Cancer Hospital, Chongqing, China; Henan Provincial Cancer Hospital, Zhengzhou, China; Yantai Yuhuangding Hospital, Yantai, China; The Second Affiliated Hospital of Army Medical University, Chongqing, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Harbin Medical University Cancer Hospital, Harbin, China; Shandong Linyi Tumor Hospital, Linyi, China; The First Affiliated Hospital of Bengbu Medical College, Bengbu, China; The First Affiliated Hospital of Soochow University, Suzhou, China; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Jiangsu Province Hospital, Nanjing, China; BetaPharma, Princeton, NJ; BetaPharma, Shanghai, China
Background: BPI-7711 is a 3rd generation irreversible EGFR-TKI that is selectively against EGFR TKI–sensitizing mutations and the T790M resistance mutations. We are conducting a phase I study to determine the safety and efficacy of BPI-7711 in patients with advanced or recurrent EGFRm+/T790M+ NSCLC. Methods: NSCLC patients who had documented disease progression after 1st/2nd generation EGFR-TKI treatment and with EGFRm+/T790M+ confirmed by central lab were enrolled in the multicenter trial (NCT03386955) into “3+3” dose escalation or expansion cohorts. BPI-7711 was orally administered at doses of 30~240 mg in capsules. Patients in dose-escalation cohorts firstly received a single dose of BPI-7711 followed by a 7-day pharmacokinetic (PK) evaluation period then received the same dose daily until disease progression or intolerable toxicity(ies) per CTCAE V4.03. Treatment efficacy per RECIST 1.1 was evaluated every 6 weeks since daily treatment commence. Once efficacy was observed in a dose, its expansion cohort was opened to enroll patients for daily treatment. Results: As of 23 December 2018, 82 patients (median age 55, 27 males, 55 females) were enrolled into 5 dose escalation cohorts (30/60/120/180/240 mg) and 4 dose expansion cohorts (30/60/120/180 mg). No DLT was observed and MTD was not reached. For all safety-evaluable patients, most common treatment emergent adverse events (TEAEs) (≥10%) were white blood cell count decreased (21.3%), neutrophil count decreased (17.3%), upper respiratory tract infection (17.3%), vomiting (12.0%) and diarrhea (10.7%), and all were Grade 1 or 2. Grade 3~4 TEAEs were occurred in 8.0% patients and 4.0% of them were treatment-related per investigators’ judgement. SAEs were reported in 4.0% of patients, and 1.3% were treatment-related. For all efficacy-evaluable patients, the overall ORR of all doses was 54.5% (30/55) including 1.8% CR and 52.7% PR. The disease control rate (DCR) was 96.4%. For patients in 120/180 mg cohorts, the ORR was 64.1% (25/39) and DCR was 97.4%. PK analyses showed BPI-7711 exposure increased in a dose-proportional manner from 30 to 180 mg after single and multiple doses. Conclusions: BPI-7711 was well tolerated and highly effective in acquired T790M+ NSCLC patients. Phase II trials are under preparation. Clinical trial information: NCT03386955