更新于：2024-11-15
Unecritinib
富马酸安奈克替尼
更新于：2024-11-15
概要
基本信息
药物类型 小分子化药 |
别名 安奈克替尼、TQ B3101、TQ-B3101 |
作用机制 ALK抑制剂(间变性淋巴瘤激酶抑制剂)、ROS1抑制剂(原癌基因酪氨酸蛋白激酶ROS抑制剂)、c-Met抑制剂(肝细胞生长因子受体抑制剂) |
原研机构 |
非在研机构- |
最高研发阶段批准上市 |
首次获批日期 中国 (2024-04-24), |
最高研发阶段(中国)批准上市 |
特殊审评特殊审批 (中国) |
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结构
分子式C23H24Cl2FN5O2 |
InChIKeyHBWSXXBJOQKNBL-CYBMUJFWSA-N |
CAS号1418026-92-2 |
关联
12
项与 富马酸安奈克替尼 相关的临床试验评价TQ-B3101胶囊治疗晚期恶性肿瘤受试者有效性和安全性的II期临床研究
A Single Center, Phase I, Open-Label, Randomized, Crossover Study to Evaluate the Effect of Food on the Pharmacokinetics of TQB3101 in Healthy Subjects
评估食物对TQ-B3101胶囊在健康成年受试者中药代动力学影响的随机、开放、单中心、两周期、两交叉I期临床试验
100 项与 富马酸安奈克替尼 相关的临床结果
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100 项与 富马酸安奈克替尼 相关的转化医学
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100 项与 富马酸安奈克替尼 相关的专利（医药）
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3
项与 富马酸安奈克替尼 相关的文献（医药）2024-08-01JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Simultaneous determination of unecritinib (TQ-B3101) and its active metabolite crizotinib in rat plasma by LC-MS/MS：An application to pharmacokinetic studies
Article
作者: Cui, Xinran ; Zhou, Jialan ; Zhang, Yuchen ; Chen, Xiaoyan ; Wang, Hong ; Chen, Huixian
Unecritinib (TQ-B3101) is a selective tyrosine kinase receptor inhibitor. In the study, in vitro metabolic experiments revealed that the hydrolysis of TQ-B3101 was mainly catalyzed by carboxylesterase 2 (CES2), followed by CES1. Next, a sensitive and reliable LC-MS/MS method was established for the simultaneous determination of TQ-B3101 and its metabolite crizotinib in rat plasma. To prevent in vitro hydrolysis of TQ-B3101, sodium fluoride, the CESs inhibitor at a concentration of 2 M, was immediately added after whole blood collection. Plasma samples were extracted by acetonitrile-induced protein precipitation method, and chromatographically separated on a Gemini C18 column (50 mm × 2.0 mm i.d., 5 μm) using gradient elution with a mobile phase of 0.1% formic acid and 5 mmol/L ammonium acetate with 0.1% formic acid. The retention times for TQ-B3101 and crizotinib were 2.61 and 2.38 min, respectively. The analytes were detected with tandem mass spectrometer by positive electrospray ionization, using the ion transitions at m/z 492.3 → 302.3 for TQ-B3101, m/z 450.3 → 260.3 for crizotinib, and m/z 494.0 → 394.3 for imatinib (internal standard). Method validation was conducted in the linear range of 1.00-800 ng/mL for the two analytes. The precision, accuracy and stabilities all met the acceptance criteria. The pharmacokinetic study indicated that TQ-B3101 was rapidly hydrolyzed to crizotinib with the elimination half-life of 1.11 h after a single gavage administration of 27 mg/kg to Sprague-Dawley rats, and the plasma exposure of TQ-B3101 was only 2.98% of that of crizotinib.
2023-06-30Signal transduction and targeted therapy
Efficacy, safety and pharmacokinetics of Unecritinib (TQ-B3101) for patients with ROS1 positive advanced non-small cell lung cancer: a Phase I/II Trial.
Article
作者: He, Jianxing ; Yu, Yan ; Fang, Yong ; Pan, Hongming ; Min, Xuhong ; Xu, Xingxiang ; Li, Man ; Yang, Zhixiong ; Lu, Shun ; Cao, Lejie ; Zhang, Jie ; Wang, Yan ; Wang, Xicheng ; Ma, Zhiyong ; Zhong, Diansheng ; Fang, Jian ; Yu, Zhuang ; Zhu, Jiajia ; Zhou, Zhen ; Cang, Shundong ; Wang, Tao ; Yang, Huaping ; Cai, Xiuyu ; Li, Kai ; Cui, Jiuwei ; Zhuang, Wu ; Wen, Xinxuan ; Wang, Xiuwen ; Li, Weidong ; Wu, Lin ; Shu, Yongqian ; Yao, Yu ; Zhang, Yang ; Shi, Jianhua
This phase I/II trial characterized the tolerability, safety, and antitumor activities of unecritinib, a novel derivative of crizotinib and a multi-tyrosine kinase inhibitor targeting ROS1, ALK, and c-MET, in advanced tumors and ROS1 inhibitor-naive advanced or metastatic non-small cell lung cancer (NSCLC) harboring ROS1 rearrangements. Eligible patients received unecritinib 100, 200, and 300 mg QD, and 200, 250, 300, and 350 mg BID in a 3 + 3 design during dose escalation and 300 and 350 mg BID during expansion. Phase II trial patients received unecritinib 300 mg BID in continuous 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) per independent review committee (IRC). Key secondary endpoints included intracranial ORR and safety. The ORR of 36 efficacy evaluable patients in the phase I trial was 63.9% (95% CI 46.2%, 79.2%). In the phase II trial, 111 eligible patients in the main study cohort received unecritinib. The ORR per IRC was 80.2% (95% CI 71.5%, 87.1%) and the median progression-free survival (PFS) per IRC was 16.5 months (95% CI 10.2, 27.0). Additionally, 46.9% of the patients who received recommended phase II dose of 300 mg BID experienced grade 3 or higher treatment-related adverse events. Treatment-related ocular disorders and neurotoxicity occurred in 28.1% and 34.4% of patients, respectively, but none was grade 3 or higher. Unecritinib is efficacious and safe for ROS1 inhibitor-naive patients with ROS1-positive advanced NSCLC, particularly patients with brain metastases at baseline, strongly supporting that unecritinib should become one of the standards of care for ROS1-positive NSCLC.ClinicalTrials.gov identifier: NCT03019276 and NCT03972189.
Frontiers in pharmacology2区 · 医学
Population Pharmacokinetic Modeling and Simulation of TQ-B3101 to Inform Dosing in Pediatric Patients With Solid Tumors
2区 · 医学
ArticleOA
作者: Xie, Simin ; Li, Su ; Wu, Huali ; Wang, Bing ; Bo, Yunhai ; Yang, Fen ; Liao, Harry ; Lu, Ye ; Pan, Hong ; Lu, Qin
Background: TQ-B3101 is a novel kinase inhibitor currently in development for the treatment of advanced malignant solid tumor and relapsed or refractory ALK-positive anaplastic large cell lymphoma.Methods: A population pharmacokinetic model was developed using data collected from a Phase 1 study and a Phase 2 study to characterize the pharmacokinetic of TQ-B3101 and its active metabolite (TQ-B3101M). The final model was used to optimize dosing of TQ-B3101 for pediatric patients (6-<18 years) with anaplastic large cell lymphoma.Results: The pharmacokinetic of TQ-B3101 and TQ-B3101M was adequately described by a 1-compartment model with first-order absorption and elimination for parent drug coupled with a 2-compartment model with time-dependent clearance for the metabolite. The clearance of TQ-B3101M decreased over time with a maximum fractional reduction of 0.41. The estimated apparent clearance and apparent volume of distribution of TQ-B3101 were 2850 L/h and 4200 L, respectively. The elimination half-life of TQ-B3101 was 1.0 h. The distribution and elimination half-lives of TQ-B3101M at steady state were 4.9 and 39.4 h, respectively. The projected exposure of TQ-B3101M in virtual pediatric population following the body surface area tiered dosing regimen was similar to that in children pediatric patients after the recommended pediatric dose of crizotinib (280 mg/m2 twice daily), an analog of TQ-B3101M.Conclusion: A population pharmacokinetic model was developed to provide optimal dose of regimen for further development of TQ-B3101 in pediatric patients with anaplastic large cell lymphoma.
100 项与 富马酸安奈克替尼 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| ROS1阳性非小细胞肺癌 | 中国 | 2024-04-24 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 非小细胞肺癌 | 临床3期 | 中国 | 2023-06-26 | |
| 晚期恶性实体瘤 | 临床2期 | 中国 | 2021-09-28 | |
| 晚期恶性实体瘤 | 临床2期 | 中国 | 2021-09-28 | |
| 局部晚期恶性肿瘤 | 临床2期 | 中国 | 2020-08-05 | |
| 晚期癌症 | 临床2期 | 中国 | 2020-07-17 | |
| 间变性大细胞淋巴瘤 | 临床2期 | 中国 | 2019-11-29 | |
| 复发性间变性大细胞淋巴瘤 | 临床2期 | 中国 | 2019-11-29 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | ROS1阳性非小细胞肺癌 ROS1 Positive | 111 | 鬱餘網艱夢餘觸襯衊憲(範醖衊鑰築糧築衊繭積) = 繭遞願鏇襯鏇夢衊簾糧 窪鹹獵壓觸築糧糧壓鏇 (網糧築襯範廠繭鹽願衊, 72.55 ~ 87.89) 更多 | 积极 | 2024-09-10 | ||
(baseline brain metastases) | 鬱餘網艱夢餘觸襯衊憲(範醖衊鑰築糧築衊繭積) = 繭廠觸艱鑰觸糧夢簾醖 窪鹹獵壓觸築糧糧壓鏇 (網糧築襯範廠繭鹽願衊, 54.48 ~ 86.70) 更多 | ||||||
临床2期 | ROS1阳性非小细胞肺癌 ROS1 Positive | 111 | 膚鑰顧鑰醖網鬱遞鹹蓋(積齋醖簾糧願窪繭餘艱) = 鹹膚鬱醖廠遞鑰廠願夢 糧糧積夢鹹遞製鬱艱齋 (築顧範築積壓構糧鏇艱, 71.5 ~ 87.1) 更多 | 积极 | 2023-06-30 | ||
临床1期 | ROS1阳性非小细胞肺癌 ROS1 Positive | 36 | 鬱廠鹽淵繭製蓋憲憲夢(鑰淵鬱夢顧鏇簾夢簾窪) = 選齋壓壓窪艱糧醖襯鬱 夢範積鏇憲範窪淵獵簾 (範醖衊網網窪餘簾膚襯, 46.2 ~ 79.2) | 积极 | 2023-06-30 | ||
临床1期 | ALK阳性间变性大细胞淋巴瘤 ALK Positive | 7 | 選鹽製齋淵鑰齋積餘壓(齋齋遞觸壓鏇繭選壓觸) = 顧壓衊餘齋夢遞糧築膚 鹹鬱鏇艱襯餘製糧餘範 (鹽觸積鬱憲艱築製獵網 ) 更多 | 积极 | 2022-12-11 | ||
临床2期 | 111 | 憲艱繭鹹餘遞獵膚選範(鏇壓鑰衊築製獵製觸構) = 觸蓋網獵襯艱艱簾壓構 襯膚網鑰築願構餘遞繭 (餘築襯夢觸膚遞憲鬱鬱, 69.6 ~ 85.6) 更多 | 积极 | 2022-03-30 | |||
临床1期 | 晚期癌症 ALK Positive | ROS1 Positive | MET Amplification | 30 | 鹽獵糧鑰鏇鹹艱膚夢繭(鏇廠襯餘餘齋齋鏇願鬱) = 醖衊鏇餘願網壓餘鑰繭 壓鹹選築積鏇蓋獵構襯 (鬱襯遞顧膚積膚廠鬱鏇 ) | 积极 | 2020-05-29 | ||
鏇壓衊鹹鑰壓遞鬱獵築(簾廠鑰襯築製鏇窪夢糧) = 積網願夢衊簾鑰糧齋遞 範艱憲夢遞築窪築獵獵 (艱壓襯鹽艱憲淵淵鑰獵 ) 更多 |
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