Clinical activity of ASP8273 in Asian patients with non‐small‐cell lung cancer with EGFR activating and T790M mutations

• DOI: 10.1111/cas.13724
• Publication Date: 2018-07-04T19:02:16Z
• Authors: Haruyasu Murakami; Hiroshi Nokihara; Hidetoshi Hayashi; Takashi Seto; Keunchil Park; Koichi Azuma; Chun‐Ming Tsai; James Chih‐Hsin Yang; Makoto Nishio; Sang‐We Kim; Katsuyuki Kiura; Akira Inoue; Koji Takeda; Jin‐Hyoung Kang; Tomoki Nakagawa; Kentaro Takeda; Rio Akazawa; Yuichiro Kaneko; Masashi Shimazaki; Satoshi Morita; Masahiro Fukuoka; Kazuhiko Nakagawa
• Keywords: Tolerability; T790M

Epidermal growth factor receptor (EGFR)-activating mutations confer sensitivity to tyrosine kinase inhibitor (TKI) treatment for non-small-cell lung cancer (NSCLC). ASP8273 is a highly specific, irreversible, once-daily, oral, EGFR TKI that inhibits both activating and resistance mutations. This dose-escalation/dose-expansion study (NCT02192697) was undertaken in two phases. In phase I, Japanese patients (aged ≥20 years) with NSCLC previously treated ≥1 received escalating doses (25-600 mg) assess safety/tolerability determine the maximum tolerated dose (MTD) and/or recommended II (RP2D) by Bayesian Continual Reassessment Method. II, adult T790M-positive Japan, Korea, Taiwan at RP2D further antitumor activity, which evaluated according Simon's two-stage design (threshold response = 30%, expected 50%, α 0.05, β 0.1). Overall, 121 (n 45 [33W/12M] n 76 [48W/28M]) 2) of ASP8273. MTD were established as 300 400 mg, respectively. As 27 63 mg achieved clinical response, determined have activity. The overall rate week 24 all 42% 32/76; 95% confidence interval, 30.9-54.0). Median duration progression-free survival 8.1 months (95% 5.6, upper bound not reached). most commonly reported treatment-related adverse event diarrhea (57%, 43/76). generally well showed activity Asian EGFR-activating T790M