This is a first-in-human, open label, single arm, sequential dose escalation and expansion study of oral DFP-11207 in patients with advanced solid tumors.

开始日期2014-06-01

申办/合作机构

Delta-Fly Pharma, Inc.

100 项与 DFP-11207 相关的临床结果

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100 项与 DFP-11207 相关的转化医学

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100 项与 DFP-11207 相关的专利（医药）

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项与 DFP-11207 相关的文献（医药）

2020-12-01·Investigational New Drugs3区 · 医学

Phase I study of DFP-11207, a novel oral fluoropyrimidine with reasonable AUC and low Cmax and improved tolerability, in patients with solid tumors

3区 · 医学

Article

作者: Anderson, Barry ; Zhang, Chun ; Eng, Cathy ; Fogelman, David ; Smith, Jackie ; Ajani, Jaffer A ; Iizuka, Kenzo ; Javle, Milind

Summary5-fluorouracil (5-FU) and 5-FU derivatives, such as capecitabine, UFT, and S-1, are the mainstay of chemotherapy treatment for gastrointestinal cancers, and other solid tumors. Compared with other cytotoxic chemotherapies, these drugs generally have a favorable safety profile, but hematologic and gastrointestinal toxicities remain common. DFP-11207 is a novel oral cytotoxic agent that combines a 5-FU pro-drug with a reversible DPD inhibitor and a potent inhibitor of OPRT, resulting in enhanced pharmacological activity of 5-FU with decreased gastrointestinal and myelosuppressive toxicities. In this Phase I study (NCT02171221), DFP-11207 was administered orally daily, in doses escalating from 40 mg/m2/day to 400 mg/m2/day in patients with esophageal, colorectal, gastric, pancreatic or gallbladder cancer (n = 23). It was determined that DFP-11207 at the dose of 330 mg/m2/day administered every 12 hours was well-tolerated with mild myelosuppressive and gastrointestinal toxicities. The pharmacokinetic analysis determined that the 5-FU levels were in the therapeutic range at this dose. In addition, fasted or fed states had no influence on the 5-FU levels (patients serving as their own controls). Among 21 efficacy evaluable patients, 7 patients had stable disease (33.3%), of which two had prolonged stable disease of >6 months duration. DFP-11207 can be explored as monotherapy or easily substitute 5-FU, capecitabine, or S-1 in combination regimens.

Drug Design, Development and Therapy3区 · 医学

Development of new promising antimetabolite, DFP-11207 with self-controlled toxicity in rodents

3区 · 医学

ArticleOA

作者: Hong, Mei ; Iizuka, Kenzo ; Jin, Cheng ; Fukushima, Masakazu ; Zhang, Chun ; Eshima, Kiyoshi

To reduce 5-fluorouracil (5-FU)-induced serious toxicities without loss of antitumor activity, we have developed DFP-11207, a novel fluoropyrimidine, which consists of 1-ethoxymethyl-5-fluorouracil (EM-FU; a precursor form of 5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP; an inhibitor of 5-FU degradation), and citrazinic acid (CTA; an inhibitor of 5-FU phosphorylation). In vitro studies of DFP-11207 indicated that it strongly inhibited the degradation of 5-FU by dihydropyrimidine dehydrogenase (DPD) in homogenates of the rat liver, and also inhibited the phosphorylation of 5-FU by orotate phosphoribosyltransferase (OPRT) in tumor tissues in a similar magnitude of potency by CDHP and CTA, respectively. Especially, DFP-11207 inhibited the intracellular phosphorylation of 5-FU in tumor cells in a dose-dependent manner whereas CTA alone did not protect intracellular 5-FU phosphorylation. These results postulate that DFP-11207 rapidly entered into the cell and the free CTA produced from DFP-11207 inhibited the phosphorylation of 5-FU in the cell. Furthermore, following oral administration of DFP-11207, CTA was found to be highly retained in the gastrointestinal (GI) tract compared to other tissues in rats. Interestingly, EM-FU, the prodrug of 5-FU was found to specifically produce 5-FU by various species of liver microsomes. When DFP-11207 was administered to rats, the plasma level of 5-FU was persisted for a long-time with lower C_max and longer half-life than that from other 5-FU prodrugs. The antitumor activity of DFP-11207 was evaluated in human tumor xenografts in nude rats and found that DFP-11207 showed an antitumor activity in a dose-dependent fashion and its efficacy is equivalent to reference 5-FU drugs. In striking contrast, DFP-11207 manifested no or less 5-FU-related toxicities, such as a decrease in body weights, GI injury, and myelosuppression, especially thrombocytopenia. Taken together, the preclinical evaluation of DFP-11207 strongly indicates that DFP-11207 be a potential new version of the oral fluoropyrimidine prodrug for further clinical development.

100 项与 DFP-11207 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
胰腺癌	临床2期	美国	Delta-Fly Pharma, Inc.	2022-01-30
胃癌	临床2期	美国	Delta-Fly Pharma, Inc.	2022-01-30
实体瘤	临床2期	美国	Delta-Fly Pharma, Inc.	2014-06-01

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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


NCT02171221 (Pubmed \| Invest New Drugs)	临床1期	实体瘤	23	DFP-11207	壓憲製範積艱獵壓範蓋(獵顧簾膚夢糧醖襯遞網) = mild 網鏇鏇簾餘積夢艱獵壓 (壓憲範簾構範憲構醖窪 ) 更多	-	2020-05-06
NCT02171221 (ASCO2019)	临床1期	实体瘤	23	DFP-11207	(齋顧構鹽鏇製淵餘繭鏇) = one pt experienced drug-related Gr3 dehydration and mucosal inflammation 夢餘願淵淵積膚窪願遞 (蓋鹹遞醖獵繭蓋鑰製憲 ) 更多	-	2019-05-26