Phase I, Open-Label, Multiple Dose, Dose-Finding and Expansion Clinical Study to Assess the Safety, Pharmacokinetics, and Efficacy of DBPR112 in Patients With Head and Neck Cancer and EGFR Mutated Lung Cancer

The study is being performed to assess the MTD, pharmacokinetics (PK), safety, tolerability and preliminary antitumor activity of DBPR112 in patients with head and neck cancer and EGFR mutated lung cancer.

开始日期2017-07-18

申办/合作机构-

100 项与 DBPR-112 相关的临床结果

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100 项与 DBPR-112 相关的转化医学

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100 项与 DBPR-112 相关的专利（医药）

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项与 DBPR-112 相关的文献（医药）

2019-11-27·Journal of Medicinal Chemistry1区 · 医学

Discovery of a Furanopyrimidine-Based Epidermal Growth Factor Receptor Inhibitor (DBPR112) as a Clinical Candidate for the Treatment of Non-Small Cell Lung Cancer

1区 · 医学

Article

作者: Wu, Su-Ying ; Chang Hsu, Yung ; Lin, Shu-Yu ; Yeh, Teng-Kuang ; Chen, Chun-Hwa ; Lin, Wen-Hsing ; Yeh, Kai-Chia ; Ke, Yi-Yu ; Hsu, Tsu-An ; Chu, Chang-Ying ; Hsieh, Hsing-Pang ; Kuo, Fu-Ming ; Lien, Tzu-Wen ; Peng, Yi-Hui ; Shiao, Hui-Yi ; Wang, Sing-Yi ; Chen, Chiung-Tong ; Sun, Hsu-Yi ; Chen, Pei-Yi ; Chen, Ching-Ping

Epidermal growth factor receptor (EGFR)-targeted therapy in non-small cell lung cancer represents a breakthrough in the field of precision medicine. Previously, we have identified a lead compound, furanopyrimidine 2, which contains a (S)-2-phenylglycinol structure as a key fragment to inhibit EGFR. However, compound 2 showed high clearance and poor oral bioavailability in its pharmacokinetics studies. In this work, we optimized compound 2 by scaffold hopping and exploiting the potent inhibitory activity of various warhead groups to obtain a clinical candidate, 78 (DBPR112), which not only displayed a potent inhibitory activity against EGFR^L858R/T790M double mutations but also exhibited tenfold potency better than the third-generation inhibitor, osimertinib, against EGFR and HER2 exon 20 insertion mutations. Overall, pharmacokinetic improvement through lead-to-candidate optimization yielded fourfold oral AUC better that afatinib along with F = 41.5%, an encouraging safety profile, and significant antitumor efficacy in in vivo xenograft models. DBPR112 is currently undergoing phase 1 clinical trial in Taiwan.

100 项与 DBPR-112 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
头颈部肿瘤	临床1期	-	National Health Research Institutes	-
肺癌	临床1期	-	National Health Research Institutes	-
EGFR突变肺癌	临床前	中国台湾	-	2017-07-18
非小细胞肺癌	临床前	中国台湾	-	2017-07-18
头颈部鳞状细胞癌	临床前	中国台湾	-	2017-07-18
肺腺癌	临床前	中国台湾	National Health Research Institutes	2014-10-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2014	临床1期	肺腺癌	-	DBPR112	蓋顧齋製齋窪積簾襯遞(壓鏇選鹹淵糧憲餘遞醖) = 廠餘選憲夢蓋壓夢餘鑰鏇鹽壓觸衊壓鏇鬱窪窪 (醖獵壓鏇築選憲夢構夢 )	积极	2014-10-01
WCLC2013	N/A	肺癌	-	DBPR112	壓鬱醖襯鏇選鏇鏇鏇鏇(選餘糧選壓鑰鬱遞獵憲) = 憲餘淵齋鬱鑰鏇鹽壓齋構觸鑰廠醖鹽顧蓋繭製 (艱遞製壓顧簾窪蓋糧憲 ) 更多	-	2013-10-29