主要研究目的：1. 定量分析男性健康受试者口服[14C]TQ-B3139后排泄物中的总放射性，获得人体放射性排泄率数据和主要排泄途径； 2. 考察男性健康受试者单次口服[14C]TQ-B3139后全血和血浆中的分配情况和血浆中总放射性的药代动力学； 3. 鉴定男性健康受试者口服[14C]TQ-B3139后人体内的主要代谢产物，确定主要生物转化途径和主要代谢产物（接近或高于10%总放射性AUC）； 4. 采用已验证的LC-MS/MS方法定量分析血浆中TQ-B3139及其代谢产物（如适用）的浓度，获得血浆中TQ-B3139及其代谢产物（如适用）的药代动力学参数；次要研究目的：观察[14C]TQ-B3139单次用药后男性健康受试者的安全性。

开始日期2022-07-04

申办/合作机构

北京赛林泰医药技术有限公司

[+1]

NCT04675060 / Unknown status临床1期

A Study of the Effect of High-fat Meal on the Pharmacokinetics of Oral TQ-B3139 Capsules in Patients With Solid Tumor

This is a study to evaluate the effect of high-fat meal on the pharmacokinetics of TQ-B3139 capsules in patients with solid tumor

开始日期2021-02-23

申办/合作机构

正大天晴药业集团股份有限公司

CTR20202043 / Completed临床1期

高脂饮食对肿瘤患者口服TQ-B3139胶囊药代动力学的影响研究

主要目的：评价高脂饮食对肿瘤患者口服 TQ-B3139 胶囊后药代动力学的影响；次要目的：评价 TQ-B3139 在肿瘤患者中的疗效和安全性。探索性目的：探索患者基因突变状态与 TQ-B3139 疗效及耐药情况之间的关系；检测 TQ-B3139 在肿瘤患者脑脊液中的浓度。

开始日期2021-02-01

申办/合作机构

北京赛林泰医药技术有限公司

[+1]

100 项与枸橼酸依奉阿克相关的临床结果

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项与枸橼酸依奉阿克相关的文献（医药）

2024-11-01·Cancer chemotherapy and pharmacology

Pharmacokinetics, mass balance, and metabolism of [14C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects

Article

作者: Wang, Xunqiang ; Wan, Xiaojing ; Wang, Xin ; Yan, Shu ; Zhang, Hua ; Yu, Ding ; Diao, Xingxing ; Ma, Sheng ; Ding, Dawei ; Miao, Liyan

PURPOSE:

Envonalkib (TQ-B3139) is a novel, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor used to treat ALK-positive non-small cell lung cancer. This phase I mass balance study investigated the pharmacokinetics, metabolism, and excretion of ¹⁴C-radiolabeled envonalkib in healthy Chinese male subjects.

METHODS:

A single oral dose of 600 mg (150 µCi) [¹⁴C]envonalkib was administered to healthy male subjects under fasted state. Samples of blood, urine and feces were collected for quantitative determination of total radioactivity and unchanged envonalkib, and the metabolites identification.

RESULTS:

After dosing, the median T_max of radioactivity was 4 h and the mean t_1/2 was 65.2 h in plasma. The exposure of total radioactivity was much higher than that of unchanged envonalkib in plasma. The mean total recovery of the radiolabeled dose was 93.93% over 504 h post-dose, with 15.23% in urine and 78.71% in feces. Envonalkib underwent extensive metabolism and a total of 15 metabolites were identified in plasma, urine, and feces. Unchanged envonalkib and its major metabolite M315 were the main components in plasma, accounting for 20.37% and 33.33% of total plasma radioactivity. In urine, O-dealkylation metabolite M315 was the major component accounted for 7.98% of dose. In feces, 16.01% of dose was excreted as cysteine conjugate M434-1. Envonalkib was well tolerated and there were no serious adverse events observed in the study.

CONCLUSION:

Envonalkib was extensively metabolized prior to excretion and eliminated primarily as metabolites via feces.

2024-08-01·Translational Lung Cancer Research

Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-naïve advanced ALK-positive non-small cell lung cancer: a systematic review and network meta-analysis

Article

作者: Wang, Chengyan ; Huang, Shanshan ; Li, Xuchang ; Xia, Yangchen ; Chu, Qian

Background:

A previous network meta-analysis (NMA) compared the efficacy of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC). The phase III INSPIRE study of iruplinalkib was published recently. The present study aimed to add the results related to iruplinalkib to the NMA.

Methods:

A systematic literature search was performed in PubMed, Embase, Cochrane Library, Google, and Baidu. Randomized controlled trials (RCTs) reporting the independent review committee-assessed progression-free survival (PFS), objective response rate (ORR), or disease control rate (DCR) results of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC were eligible for inclusion in the NMA. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Bayesian fixed-effect models were used for the direct and indirect pairwise comparisons. This study was registered with PROSPERO (CRD42024555299).

Results:

Eight studies, involving 1,477 Asian patients and seven treatments (crizotinib, alectinib, brigatinib, ensartinib, envonalkib, iruplinalkib, and lorlatinib), were included in the NMA. In terms of the overall risks of bias, all of the studies had "some concerns". All the next-generation ALK inhibitors were statistically superior to crizotinib in terms of PFS. Iruplinalkib had the best surface under the cumulative ranking curve (74.0%), followed by brigatinib (69.1%) and ensartinib (63.7%). Most of the pairwise comparisons did not reveal significant differences in the ORR and DCR. In terms of both the ORR and DCR, alectinib ranked first, followed by lorlatinib.

Conclusions:

Next-generation ALK inhibitors had better efficacy than crizotinib in the treatment of Asian patients with ALK inhibitor-naïve advanced ALK-positive NSCLC. Iruplinalkib may have more favorable PFS benefit than other ALK inhibitors for Asians.

2022-09-01·European journal of cancer (Oxford, England : 1990)

First-in-human phase I study of TQ-B3139 (CT-711) in advanced non-small cell lung cancer patients with ALK and ROS1 rearrangements

Article

作者: Zhang, Zhonghan ; Zhang, Yang ; Wan, Xiaojing ; Yang, Haiyan ; Pan, Hui ; Li, Su ; Fang, Wenfeng ; Liu, Jingwen ; Wang, Xunqiang ; Zhang, Yongchang ; Han, Xi ; Liu, Li ; Xiong, Yi ; Yang, Nong ; Zhao, Yuanyuan ; Zhang, Li ; Zhao, Hongyun ; Ma, Yuxiang ; Zhou, Chunhua ; Hong, Shaodong ; Zeng, Liang ; Huang, Yan ; Shao, Yang ; Xue, Jinhui ; Yang, Yunpeng

BACKGROUND:

TQ-B3139 is a novel ALK tyrosine kinase inhibitor (TKI) against a broad range of ALK mutations. The aim of this first-in-human phase I trial was to investigate the safety, tolerability, pharmacokinetics, and clinical efficacy of TQ-B3139 in ALK or ROS1 positive advanced NSCLC patients.

METHODS:

Following a 3 + 3 design, patients received escalating daily dose of TQ-B3139 (50-800 mg) continuously in 28-day cycles. Expansion stage started at dose of 200 mg twice daily (BID). The primary objectives were the safety, dose-limited toxicities (DLT) and recommended phase II dose (RP2D); secondary objectives included pharmacokinetics and antitumor activity. Non-obligatory tumor samples at baseline were collected and sequenced.

RESULTS:

The study enrolled 63 patients. Fifty-nine (93.4%) patients experienced treatment-related adverse events (TRAEs), mostly grade 1-2 vomiting (79.3%), diarrhea (76.1%) or nausea (68.2%). 1 (1/6) DLT occurred at 600 mg BID and 1 (1/3) at 800 mg BID. Based on safety and pharmacokinetics data, the RP2D was selected as 600 mg BID. At a dose level ≥200 mg BID, the overall response rate (ORR) was 76.7% (33/43), and the median progression free survival (mPFS) was 25.2 months (95%CI 11.9-NR) for TKI-naive patients. For TKI-treated patients, the ORR was 37.5% (6/16), and the mPFS was 5.4 months (95%CI 3.6-9.1). The ORR was 66.7% (2/3) in patients with ROS1 fusion at dose level ≥200 mg BID. In patients with measurable brain metastases, the intracranial ORR was 70% (7/10), with median intracranial PFS of 15.9 months. In TKI-treated patients, variant 3 and TP53 alteration were associated with poor PFS.

CONCLUSIONS:

TQ-B3139 was well-tolerated and exhibited promising anti-tumor activities in patients with ALK and ROS1 positive advanced NSCLC.

CLINICAL TRIAL NUMBER:

NCT03099330.

102

项与枸橼酸依奉阿克相关的新闻（医药）

2024-11-11

·药筛

正大天晴 1类新药格索雷塞片，江苏华阳比拉斯汀片首仿获批上市 | 新产品

今日NMPA新批文很多。正大天晴再收获一枚1类新药，格索雷塞片，用于KRAS-G12C 突变型的晚期非小细胞肺癌，今年第四款1类新药，前面3个是安奈克替尼、依奉阿克、贝莫苏拜单抗。江西药都樟树制药的经典名方二冬汤颗粒获批上市，二冬汤为国家中医药管理局发布的《古代经典名方目录(第一批)》第80首，出自清•程国彭《医学心悟》卷三，由天冬、麦冬、天花粉、黄芩、知母、荷叶、人参和甘草等组成，具有润肺清胃之功效。主治上消，症见烦渴不止、小便频数、脉数无力等。江苏华阳的比拉斯汀片获批上市，国内首仿。比拉斯汀片是一种第二代非镇静性的长效抗组胺药物，用于青少年和成年人荨麻疹。相关阅读：这个凝胶贴膏，再次被否了 | 新产品柯菲平凯普拉生新适应症获批，亚虹灌注用盐酸氨酮戊酸己酯获批上市 | 新产品两个热门品种，6个上市申请被团灭 | 新产品第十批国采分享微信群已建，欢迎企业和代理商入群，对接资源，先到先得了。加客服小狐微信，拉你入群！

上市批准

2024-11-11

·米内网

【重磅】正大天晴1类新药获批，掘金1400亿市场

精彩内容 11月11日，国家药监局发布最新药品获批信息，正大天晴联合开发的格索雷塞片获批上市，这是正大天晴今年获批的第四款1类新药，也是公司在抗肿瘤药市场的又一突破。图1：正大天晴最新获批的产品来源：国家药监局官网资料显示，2023年8月正大天晴与益方生物签订许可与合作协议，获得了格索雷塞片在中国大陆地区开发、注册、生产和商业化的独家许可权。格索雷塞片是一款新型、高效的KRAS G12C抑制剂，可抑制KRAS G12C的致癌信号传导，抑制肿瘤细胞增殖，从而实现抗肿瘤作用，本次获批的适应症为用于治疗至少接受过一种系统性治疗的KRAS G12C突变型的晚期非小细胞肺癌(NSCLC)成人患者。据悉，正大天晴正在与益方生物合作推进格索雷塞在一线NSCLC、胰腺癌、结直肠癌等多个实体肿瘤中的临床试验，有望打造出下一个比肩安罗替尼级别的重磅肿瘤产品。表1：2024年至今正大天晴获批的1类新药（按批文统计）来源：米内网中国申报进度（MED）数据库米内网数据显示，2024年至今正大天晴收获了多款创新药，包括了化药1类新药富马酸安奈克替尼胶囊、枸橼酸依奉阿克胶囊和格索雷塞片，以及生物药1类新药贝莫苏拜单抗注射液，4款1类新药均为抗肿瘤药。图2：中国三大终端六大市场（化+生）抗肿瘤药的销售情况（单位：万元）来源：米内网格局数据库 2023年在中国三大终端六大市场（化+生）抗肿瘤药的市场规模突破1400亿元，2024上半年增长率为10.33%。在多款1类新药的助力下，正大天晴在抗肿瘤药市场的地位有望不断提升。表2：正大天晴部分报产在审的1类新药来源：米内网中国申报进度（MED）数据库抗肿瘤药库莫西利胶囊是新型CDK2/4/6抑制剂，研究结果显示，与阿贝西利相比，库莫西利对CDK2的抑制作用进一步提升，其增强的CDK2和CDK4抑制活性可能有助于在临床上克服目前CDK4/6抑制剂的耐药性问题。库莫西利作为一款活性和选择性更优的新型CDK2/4/6抑制剂，将为HR+/HER－乳腺癌患者提供新的治疗选择，也将成为正大天晴下一个获批的重磅抗肿瘤1类新药。资料来源：国家药监局官网、米内网数据库注：米内网《中国三大终端六大市场药品竞争格局》，统计范围是：城市公立医院和县级公立医院、城市社区中心和乡镇卫生院、城市实体药店和网上药店，不含民营医院、私人诊所、村卫生室，不含县乡村药店；上述销售额以产品在终端的平均零售价计算。数据统计截至11月11日，如有疏漏，欢迎指正。本文为原创稿件，转载请注明来源和作者，否则将追究侵权责任。投稿及报料请发邮件到872470254@qq.com稿件要求详询米内微信首页菜单栏商务及内容合作可联系QQ：412539092 ●温馨提示● 因为微信公众号修改了推送规则，最近很多读者反映没有及时看到推文。把米内网设为“星标”，就能每天与我们不见不散啦，具体操作如下：【分享、点赞、在看】点一点不失联哦

上市批准

2024-11-08

·医药魔方Info

专利事件| 维得利珠单抗登记专利无效结案，赛立奇单抗首次登记1件序列结构专利

为助力医药行业专利从业者第一时间获取最新专利事件及进展，医药魔方推出了专利事件栏目，将每周对药品相关重要专利事件进行汇总，主要涉及：专利登记/声明、药品专利到期、专利复审与无效、专利PTE/PTA获批等情报。专利情报数据均来源于医药魔方NextPat数据库。本周（2024.10.28-2024.11.03）主要涉及以下内容： 1.中国上市药品专利登记及仿制药专利声明重点内容简介：本周CDE中国上市药品专利信息登记平台新增登记药品专利5件。8月份新获批上市的国产创新药赛立奇单抗注射液首次登记了1件序列结构专利。正大天晴药业将枸橼酸依奉阿克胶囊的晶型专利、富马酸安奈克替尼胶囊的晶型专利新增登记到平台中等。本周2类、3类、4类声明中唯一涉及的生物药是帕妥珠单抗注射液，杭州博之锐生物对帕妥珠单抗的6件登记专利进行了声明，此前已经有齐鲁制药、正大天晴药业提交申报上市，登记专利中的3件此前遭到过齐鲁或正大天晴的无效挑战，1件被宣告部分无效，2件被全部无效。 2.美国FDA桔皮书、紫皮书、美国PTE专利新增重点内容简介：本周FDA桔皮书新增专利数十件，本周FDA桔皮书新增专利数十件，涉及品种Cycloset（溴隐亭）、Caplyta（卢美哌隆）、Orilissa（恶拉戈利）、Artesunate（青蒿琥酯）、Cobenfy（呫诺美林+曲司氯铵）等。 3. 中国药品专利复审、无效情况精选重点内容简介：本周精选的数件药品相关专利有复审决定发文或在驳回后提交了复审请求，涉及达雷妥尤单抗+重组人玻璃酸酶、维拉卡肽、卡格列净等。本周内有1件药品相关专利无效决定发文，烟台蓝纳成生物的临床1期管线177Lu-LNC1003的核心化合物专利被维持专利权有效。维得利珠单抗的一件医药用途专利迎来一份无效宣告案件结案通知书，应是请求人撤回了无效请求。 4. 中国药品专利PTE、PTA情况精选重点内容简介：本周有多件专利权期限补偿审批决定发文，多个药品相关专利获批专利权期限延长，列举了部分本周获批PTA的药品相关专利，涉及lorigerlimab、subasumstat、艾贝司他、dapiglutide等。药品专利事件周报的详细内容请点击阅读原文查看，或者加入文末医药魔方专利信息群获取。医药魔方专利信息群，旨在提供医药行业专利重点事件监控和解读，群内提供以下信息： 1. 及时的医药专利无效信息、复审跟踪、PTE/PTA专利补偿提醒； 2. 中国上市药品专利登记平台最新登记/声明； 3. 桔皮书专利最新登记； 4. 热点医药专利事件解读； 5. 医药专利研究报告； 6. 医药专利相关资讯。目前免费开放中（限前500人）添加左下方微信号，备注“专利-公司-职位"，拉您进群；如想申请NextPat数据库试用，可扫右侧二维码申请试用。

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研发状态

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10 条最早获批的记录,

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适应症	国家/地区	公司	日期
ALK阳性非小细胞肺癌	中国	正大天晴药业集团股份有限公司	2024-06-11

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10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
MET基因扩增非小细胞肺癌	临床2期	中国	正大天晴药业集团股份有限公司	2020-08-11
晚期恶性实体瘤	临床1期	中国	正大天晴药业集团股份有限公司	2021-02-01
晚期癌症	临床1期	中国	正大天晴药业集团股份有限公司	2017-07-12

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临床结果

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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


NCT04009317 (Pubmed)	临床3期	ALK阳性非小细胞肺癌一线	264	Envonalkib	網網築餘積壓淵廠壓蓋(醖簾鏇膚壓製淵選獵衊) = 鹽選選積鹹繭構網繭繭鏇觸襯衊餘艱範憲繭襯 (糧範淵鬱壓憲壓醖鑰積 ) 更多	积极	2023-08-14
				Crizotinib	網網築餘積壓淵廠壓蓋(醖簾鏇膚壓製淵選獵衊) = 廠窪醖積餘蓋醖醖淵壓鏇觸襯衊餘艱範憲繭襯 (糧範淵鬱壓憲壓醖鑰積 ) 更多
NCT04009317 (ESMO_ASIA2022) 人工标引	临床3期	ALK阳性非小细胞肺癌一线	264	Envonalkib 600mg (overall)	艱築膚築選獵鹽夢憲選(獵憲築淵壓範艱鹹遞選) = 範蓋鏇鏇顧製壓顧夢壓餘製襯憲鏇膚構鬱鑰鹽 (繭繭餘積淵鏇鏇積衊遞 ) 更多	优效	2022-12-03
				crizotinib 250mg (overall)	艱築膚築選獵鹽夢憲選(獵憲築淵壓範艱鹹遞選) = 襯簾選淵衊廠構窪選鹹餘製襯憲鏇膚構鬱鑰鹽 (繭繭餘積淵鏇鏇積衊遞 ) 更多
NCT03099330 (Pubmed)	临床1期	晚期癌症	63	TQ-B3139	淵廠齋鏇鬱積積遞獵窪(鑰構簾廠夢艱選鑰齋糧) = 76.1% 顧繭衊鏇蓋窪壓觸積範 (廠醖餘膚鬱網膚遞選獵 ) 更多	积极	2022-08-05