马来酸奈拉替尼(Neratinib maleate) - 药物靶点：EGFR x HER2 x HER4_在研适应症：早期乳腺癌，乳腺癌，HER2阳性乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

neratinib、Nerlynx、来那替尼

+ [8]

靶点

EGFR x HER2 x HER4

作用机制

EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、HER2拮抗剂(受体蛋白酪氨酸激酶 erbB-2拮抗剂)、HER4拮抗剂(受体蛋白酪氨酸激酶 erbB-4拮抗剂)

治疗领域

肿瘤皮肤和肌肉骨骼疾病神经系统疾病+ [3]

在研适应症

早期乳腺癌乳腺癌HER2阳性乳腺癌+ [24]

非在研适应症

晚期乳腺癌晚期 HER2 阳性乳腺癌晚期非小细胞肺癌+ [8]

原研机构

Pfizer Inc.

在研机构

Pierre Fabre Médicament SAS

Puma Biotechnology, Inc.

甫康（上海）健康科技有限责任公司

+ [7]

非在研机构-

最高研发阶段批准上市

首次获批日期

美国 (2017-07-17),

HER2 阴性乳腺癌

最高研发阶段(中国)批准上市

特殊审评快速通道 (美国)、孤儿药 (美国)

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结构

分子式C34H33ClN6O7

InChIKeyVXZCUHNJXSIJIM-MEBGWEOYSA-N

CAS号915942-22-2

关联

115

项与马来酸奈拉替尼相关的临床试验

NCT05919108 / Recruiting临床2期IIT

Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers

This phase II trial tests how well neratinib prior to the primary treatment (neoadjuvant) works in treating patients with stage I-III HER2 mutated lobular breast cancers. Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving neratinib in addition to normal therapy may work better in treating cancer than the endocrine therapy patients would normally receive.

开始日期2024-09-30

申办/合作机构

The Vanderbilt-Ingram Cancer Center

[+2]

NCT05615818 / Recruiting临床3期

Molecular Targeted Maintenance Therapy Versus Standard of Care in Advanced Biliary Cancer: an International, Randomised, Controlled, Open-label, Platform Phase 3 Trial

The object of this trial is to evaluate whether the introduction of a targeted therapy after 4 cycles of the current standard-of-care treatment for advanced biliary cancer is superior to continuing with the standard treatment.
The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, during which a molecular profile of the patient's tumour will be obtained, and (ii) a randomised comparative trial in which patients with disease control after 4 cycles of standard treatment, and whose tumour harbours a targetable molecular alteration, will be randomised (2:1) to receive either a matched targeted therapy or to continue with the standard treatment.

开始日期2024-05-29

申办/合作机构

UNICANCER

[+8]

NCT06126276 / Recruiting临床2期IIT

A Randomized Trial of Neratinib, A Pan-ERBB Inhibitor, Alone or in Combination With Palbociclib, a CDK4/6 Inhibitor, in Patients With HER2+ Gynecologic Cancers and Other Solid Tumors: A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial compares the effect of neratinib to the combination of neratinib and palbociclib in treating patients with HER2 positive solid tumors. Neratinib and palbociclib are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving neratinib and palbociclib in combination may shrink or stabilize cancers that over-express a specific biomarker called HER2.

开始日期2024-05-07

申办/合作机构

National Cancer Institute

100 项与马来酸奈拉替尼相关的临床结果

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100 项与马来酸奈拉替尼相关的转化医学

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100 项与马来酸奈拉替尼相关的专利（医药）

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531

项与马来酸奈拉替尼相关的文献（医药）

2024-03-01·European journal of cancer (Oxford, England : 1990)

Revolutionizing anti-HER2 therapies for extrahepatic cholangiocarcinoma and gallbladder cancer: Current advancements and future perspectives

Review

作者: Pedregal, Manuel ; Prato, Javier ; Moreno, Victor ; Lamarca, Angela ; Klümpen, Heinz-Josef ; Ten Haaft, Britte Hea

Biliary tract cancers (BTCs) encompass a heterogeneous group of rare tumors, including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC) and ampullary cancer (AC). The present first-line palliative treatment regimen comprises gemcitabine and cisplatin in combination with immunotherapy based on two randomized controlled studies. Despite the thorough investigation of these palliative treatments, long-term survival remains low. Moving beyond conventional chemotherapies and immunotherapies, the realm of precision medicine has demonstrated remarkable efficacy in malignancies such as breast and gastric cancers, characterized by notable HER2 overexpression rates. In the context of biliary tract cancer, significant HER2 alterations are observed, particularly within eCCA and GBC, heightening the interest in precision medicine. Various anti-HER2 therapies, including trastuzumab, pertuzumab, trastuzumab-deruxtecan, zanidatamab and neratinib, have undergone investigation. The objective of this review is to summarize the current evidence and outline future directions of targeted HER2 treatment therapy in patients with biliary tract tumors, specially extrahepatic cholangiocarcinoma and gallbladder cancer.

2024-02-01·Anti-cancer drugs

Autophagy as a therapeutic mechanism to kill drug-resistant cancer cells

Article

作者: Roberts, Jane L ; Poklepovic, Andrew ; Dent, Paul ; Booth, Laurence

Herein we discuss multiple pre-clinical projects developed by our group that have been translated into patients at Massey Cancer Center. Our work has used multi-kinase inhibitors, for example, sorafenib, regorafenib and neratinib, and combined with additional agents, for example, histone deacetylase inhibitors, the thymidylate synthase inhibitor pemetrexed, and PDE5 inhibitors. In broad-brush terms, our experience has been that these drug combinations enhance signaling by ATM-AMPK-ULK-1 and decrease signaling from growth factor receptors and RAS proteins, thereby lowering the activities of the intracellular signaling kinase ERK1/2, AKT, mTOR and p70S6K. This collectively results in reduced protein synthesis and the induction of an endoplasmic reticulum stress response alongside autophagosome formation and autophagic flux. The rupture of autolysosomes, releasing proteases such as cathepsin B into the cytosol results in the cleavage and activation of the toxic BH3 domain protein BID which cooperates with BAX, BAK and BIM to cause mitochondrial dysfunction, leading to the release of cytochrome c and AIF, which then execute the tumor cell. For each of our two-drug combinations, we then performed additional laboratory-based studies to define the development of evolutionary resistance mechanisms, with the long-term concept of performing new three-drug clinical trials to prolong therapeutic efficacy and disease control.

2024-02-01·Gynecologic oncology

Targeting HER2-mutant metastatic cervical cancer with neratinib: Final results from the phase 2 SUMMIT basket trial

Article

作者: Goldman, Jonathan ; Eli, Lisa D ; Melisko, Michelle E ; Panni, Stefano ; Ravichandran, Vignesh ; Frazier, Aimee L ; D'Souza, Anishka ; Oaknin, Ana ; de Miguel, Maria ; Friedman, Claire F ; DiPrimeo, Daniel ; Gambardella, Valentina ; Tinker, Anna V ; Spanggaard, Iben ; Loi, Sherene ; ElNaggar, Adam C ; Solit, David B ; Shapiro, Geoffrey I ; Bello Roufai, Diana

OBJECTIVE:

HER2 mutations are associated with poor prognosis and are detected in 3-6% of cervical cancers. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, had activity in several HER2-mutant cancer types in the phase 2 SUMMIT basket study. We present updated and final results from the cervical cancer cohort of SUMMIT.

METHODS:

Eligible patients had HER2-mutant, metastatic or recurrent cervical cancer progressing after platinum-based treatment for advanced/recurrent disease. Patients received neratinib 240 mg/day; loperamide was mandatory during cycle 1. Confirmed objective response rate (ORR) was the primary endpoint. Duration of response (DoR), clinical benefit rate (CBR), progression-free survival (PFS), and safety were secondary endpoints.

RESULTS:

Twenty-two patients were enrolled; 18 (81.8%) had endocervical adenocarcinoma; median two prior systemic chemotherapy regimens (range 1-4). The most common HER2 variant was S310F/Y mutation (n = 13; 59.1%). Four patients had confirmed partial responses (ORR 18.2%; 95% CI 5.2-40.3); 6 had stable disease ≥16 weeks (CBR 45.5%; 95% CI 24.4-67.8). Median DoR was 7.6 months (95% CI 5.6-12.3). Median PFS was 5.1 months (95% CI 1.7-7.2). All-grade diarrhea (90.9%), nausea (54.5%), and constipation (54.5%) were the most common adverse events. Five patients (22.7%) reported grade 3 diarrhea. There were no grade 4 adverse events, no diarrhea-related treatment discontinuations, and two grade 5 adverse events, unrelated to neratinib: dyspnea (n = 1) and embolism (n = 1).

CONCLUSIONS:

Neratinib resulted in durable responses and disease control in patients with HER2-mutant metastatic/recurrent cervical cancer in SUMMIT. These findings support next-generation sequencing and tailored therapy for select patients with advanced cervical cancer. All responses occurred in patients with endocervical adenocarcinoma. Further assessment of neratinib in this setting is warranted.

TRIAL REGISTRATION NUMBER:

NCT01953926 (ClinicalTrials.gov), 2013-002872-42 (EudraCT).

150

项与马来酸奈拉替尼相关的新闻（医药）

2024-06-18

·精准药物

浅析HER2选择性小分子结构特征

这里“HER2选择性”，主要指对EGFRWT的选择性，因二者为同一家族，结合口袋相似性高，之前获批的HER2小分子抑制剂如Lapatinib、Neratinib，都是EGFR/HER2双重抑制剂，由于较强抑制EGFRWT，治疗窗口比较窄，dose上不去。直到2020年Tucatinib获批上市。 Tucatinib是目前唯一上市的选择性HER2小分子抑制剂，由Array公司研发，授权给Seagen (Seattle Genetics)，而后来Array与Seagen先后被辉瑞收购。下图由公众号“新药故事”整理，Lapatinib与Neratinib是EGFR/HER2双抑制剂 (其中Nera为共价分子)，Tucatinib是第一款选择性HER2抑制剂，三者都已上市。后面两个分别为迪哲与赞荣的专利分子，亦是选择性HER2抑制剂。下图也由“新药故事”分享，是一家AI公司Iambic的专利分子，其亦有HER2选择性抑制剂管线。从以上分子可以注意到HER2选择性抑制剂的一处关键，即在第一张图Tucatinib结构式中圈起来的部分。该片段或相似片段被后续HER2选择性分子沿用。包括上面以及下面的例子。下图是Dana-Farber研究中心发表的文献分子，Tucatinib与Neratinib的hybridization。下图是BI公司的分子，前两个是文献分子，第三个已经三期临床。下图是辉瑞公司近日发表的文献分子。综上，可以看出之前highlight过的片段 (或相似片段)，是HER2选择性抑制剂的一个共同特征。下面数据进一步证实五元杂环对HER2选择性的重要。有结合模式就容易理解。杂环指向一处差异残基，其在EGFR中为Cysteine，在HER2中为Serine。在HER2中S783与杂环N形成一个氢键。下图表数据进一步证明该处差异残基的影响。当人为突变EGFR相对应残基C775为Serine (模拟HER2)，与HER2该位点形成氢键的小分子如BI-1622对EGFR的活性明显增强。综上，HER2选择性主要来源于杂环与S783之间形成的氢键，而EGFR中对应位置的残基是C775，即使与杂环形成氢键也弱得多，估算二者差异在3.2-3.9 Kcal/mol之间，对应220-720倍活性差距。而再回头看分子3、4的SAR，加上杂环之后选择性改善一方面由于HER2活性提高，但更因为EGFR活性下降，说明什么呢？请考虑desolvation的影响。最后，目前HER2小分子抑制剂的研发可能主要围绕对EGFRWT选择性及脑渗透两个方面，共价方面有的选择共价有的不共价。分子结构上从个人看到的这些分子 (对该靶点无深入研究)，都沿用了图1 Tucatinib圈起来的片段 (或有改动)，Array公司当年的这一改动 (Tucatinib可能也是在Lapatinib基础上发现的)，不仅成就了一个上市药物，也启发了后来者们。 Iambic的HER2选择性抑制剂，AI设计的？公众号“新药故事” https://www-nature-com.libproxy1.nus.edu.sg/articles/s43018-022-00412-y (2022) 内容来源于网络，如有侵权，请联系删除。

并购临床失败

2024-06-07

·BioSpace

Puma Biotechnology Reports Inducement Awards Under Nasdaq Listing Rule 5635(c)(4) - June 07, 2024

LOS ANGELES--(BUSINESS WIRE)-- Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, announced that on June 6, 2024, the Compensation Committee of Puma’s Board of Directors approved the grant of an inducement restricted stock unit award covering 3,500 shares of Puma common stock to one new non-executive employee. The award was granted under Puma’s 2017 Employment Inducement Incentive Award Plan, which was adopted on April 27, 2017 and provides for the granting of equity awards to new employees of Puma. The restricted stock unit award vests over a three-year period, with one-third of the shares underlying the award vesting on the first anniversary of the award’s vesting commencement date, June 1, 2024, and one-sixth of the shares underlying the award vesting on each six-month anniversary of the vesting commencement date thereafter, subject to continued service. The award was granted as an inducement material to the new employee entering into employment with Puma, in accordance with Nasdaq Listing Rule 5635(c)(4). About Puma Biotechnology Puma Biotechnology, Inc. is a biopharmaceutical company with a focus on the development and commercialization of innovative products to enhance cancer care. Puma in-licensed the global development and commercialization rights to PB272 (neratinib, oral), in 2011. Neratinib, oral was approved by the U.S. Food and Drug Administration in 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy, and is marketed in the United States as NERLYNX® (neratinib) tablets. In February 2020, NERLYNX was also approved by the FDA in combination with capecitabine for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. NERLYNX was granted marketing authorization by the European Commission in 2018 for the extended adjuvant treatment of adult patients with early stage hormone receptor-positive HER2-overexpressed/amplified breast cancer and who are less than one year from completion of prior adjuvant trastuzumab-based therapy. NERLYNX® is a registered trademark of Puma Biotechnology, Inc. In September 2022, Puma entered into an exclusive license agreement for the development and commercialization of the anti-cancer drug alisertib, a selective, small molecule, orally administered inhibitor of aurora kinase A. Initially, Puma intends to focus the development of alisertib on the treatment of small cell lung cancer and breast cancer. In February 2024, Puma initiated ALISCA-Lung 1, a Phase II clinical trial of alisertib monotherapy for the treatment of patients with extensive-stage small cell lung cancer. View source version on businesswire.com: Contacts Alan H. Auerbach or Mariann Ohanesian, Puma Biotechnology, Inc., +1 424 248 6500 info@pumabiotechnology.com ir@pumabiotechnology.com Source: Puma Biotechnology, Inc. View this news release online at:

上市批准引进/卖出临床2期

2024-06-06

·美通社

皮尔法伯实验室宣布提交关于一种针对实体瘤（包括伴 MET 异常的非小细胞肺癌）患者的潜在治疗 PFL-002/VERT-002 的 IND 申请

法国卡斯特尔 2024年6月6日 /美通社/ -- 皮尔法伯实验室于今日宣布向美国食品药品监督管理局（"FDA"）提交一份新药临床试验（"IND"）申请，以启动 PFL-002/VERT-002 治疗实体瘤（包括非小细胞肺癌 (NSCLC)）的首次人体 (FIH) I/II 期临床试验。 PFL-002/VERT-002 I/II 期试验是一项多中心国际研究，旨在评估 PFL-002/VERT-002 在伴 MET 异常的 NSCLC 患者，包括对其他治疗产生耐药机制的患者中的安全性、耐受性、药代动力学 (PK)、药效学 (PD) 和初步疗效。FDA 将审查该申请并确定其可接受性。皮尔法伯实验室医疗保健研发部主管 Francesco Hofmann 表示："我们期待在今年下半年启动 PFL-002/VERT-002 的首次人体试验。该新药是一种具有差异化作用机制的新型治疗方案，用于治疗包括 NSCLC 在内的伴 MET 异常实体瘤患者，我们坚信它拥有广阔前景。" 关于 PFL-002/VERT-002 PFL-002/VERT-002 是由 Vertical Bio 开发的一种单克隆抗体，其具有独特的差异化作用机制，能够降解已知存在于实体瘤（包括伴 MET 突变或扩增的非小细胞肺癌 (NSCLC)）患者体内的疾病驱动因素： c-MET 。Vertical Bio 已被皮尔法伯实验室收购，并已完成该抗体的临床前优化工作。皮尔法伯实验室正在推进 PFL-002/VERT-002 的临床开发，并希望于 2024 年底之前为 FIH 试验招募到首例患者。关于皮尔法伯研发管线和产品组合皮尔法伯实验室在其研发管线中新增了几项资产，从而扩大了在精准肿瘤学领域的投入。该实验室将与 Scorpion Therapeutics 合作开发两种用于治疗 EGFR 驱动性非小细胞肺癌 (NSCLC) 患者的突变选择性 EGFR 抑制剂：PFL-241/STX-241 和 PFL-721/STX-721。通过收购 Vertical Bio，皮尔法伯实验室将针对 PFL-002/VERT-002 治疗 MET 基因异常驱动性实体瘤开展临床试验。最近，该实验室从 Kinnate Biopharma 购得泛 RAF 抑制剂 exarafenib，旨在扩展 RAS/RAF 驱动性实体瘤的靶向治疗方案。这些新增的临床开发产品组合分别通过 encorafenib、binimetinib 和来那替尼补充了皮尔法伯实验室现有的靶向 BRAF、MEK、HER2 的精准肿瘤学产品组合。 PDF - https://mma.prnewswire.com/media/2430129/Pierre_Fabre_filing.pdf Press contact: Laurence Marchal laurence.marchal@pierre-fabre.com

临床申请并购

100 项与马来酸奈拉替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	马来酸奈拉替尼	L01XE45	DB11828

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
早期乳腺癌	韩国	Bixink, Inc.	2021-10-19
乳腺癌	澳大利亚	Specialised Therapeutics Australia Pty Ltd.	2019-03-15
HER2阳性乳腺癌	欧盟	Pierre Fabre Médicament SAS	2018-08-31
HER2阳性乳腺癌	冰岛	Pierre Fabre Médicament SAS	2018-08-31
HER2阳性乳腺癌	列支敦士登	Pierre Fabre Médicament SAS	2018-08-31
HER2阳性乳腺癌	挪威	Pierre Fabre Médicament SAS	2018-08-31
HER2 阴性乳腺癌	美国	Puma Biotechnology, Inc.	2017-07-17

未上市

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
HER2阳性转移性乳腺癌	临床3期	美国	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	日本	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	阿根廷	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	澳大利亚	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	奥地利	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	比利时	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	巴西	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	加拿大	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	捷克	Puma Biotechnology, Inc.	2013-03-29
HER2阳性转移性乳腺癌	临床3期	丹麦	Puma Biotechnology, Inc.	2013-03-29

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临床结果

适应症

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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


NCT06083662 (KCSG AL20-17, ASCO2024)	临床2期	晚期恶性实体瘤 HER2 mutation in the kinase domain	40	Neratinib 240mg p.o. daily + Trastuzumab biosimilar (Herzuma) every 3 weeks	範襯遞積願膚膚膚艱艱(鹽淵範膚淵構窪鏇壓膚) = 廠憲製網簾憲憲窪範膚膚製製製淵鹽築鬱餘積 (餘衊顧願選醖繭顧餘蓋, 0 ~ 22.63) 更多	积极	2024-05-24
ASCO2024	N/A	HER2阳性癌症新辅助	43	Neratinib plus Trastuzumab and Docetaxel (N+TDtx)	鑰鏇鏇構壓鑰憲網範壓(醖糧築繭顧壓膚衊鑰窪) = 鑰鬱艱鬱範網壓鑰醖鹽鏇繭鏇壓獵蓋築鑰製醖 (膚遞醖鏇醖構繭艱餘鬱 ) 更多	积极	2024-05-24
				Pertuzumab plus Trastuzumab and Docetaxel (PT+Dtx)	鑰鏇鏇構壓鑰憲網範壓(醖糧築繭顧壓膚衊鑰窪) = 築淵鬱餘窪鬱艱簾製淵鏇繭鏇壓獵蓋築鑰製醖 (膚遞醖鏇醖構繭艱餘鬱 ) 更多
NCT01494662 (TBCRC 022, CTgov)	临床2期	HER2阳性乳腺癌 \| 脑转移瘤	140	HKI-272 (Cohort 1)	鑰餘壓築願糧簾顧鏇築(壓艱窪醖積願壓鬱製艱) = 鹹憲顧選網願夢構製製醖膚鹽襯蓋淵壓願構淵 (繭糧顧衊願鏇選築築襯, 憲範鹽顧夢選壓夢獵鏇 ~ 廠鬱繭遞壓鹽壓鬱憲淵) 更多	-	2024-05-22
				Surgical Resection (Cohort 2)	鬱壓糧鹽蓋簾艱艱積襯(鬱艱艱淵鏇選構製網簾) = 願積遞餘網選糧壓膚糧積夢衊範鑰鑰願窪鑰簾 (窪鹽積簾襯獵鬱願遞願, 襯齋鹽壓夢襯製顧簾鬱 ~ 積鑰窪醖鑰齋製餘淵製) 更多
NCT04388384 (ELEANOR NIS, ESMO_BC2024) 人工标引	N/A	HER2阳性乳腺癌辅助 HER2 Positive	286	Neratinib	餘獵遞鬱襯廠淵鏇鬱襯(觸膚糧積餘鏇壓鹽夢艱) = most common adverse events of any grade in >10% pts were diarrhoea, nausea and fatigue with 81.3%, 22.2%, 19.8% respectively. 鏇鬱廠鑰獵窪夢鏇艱製 (鏇製膚糧醖顧觸獵醖範 )	积极	2024-05-15
NCT05599334 (NEAR, ESMO_BC2024) 人工标引	N/A	HER2阳性乳腺癌辅助 HER2 Positive	108	Neratinib	壓糧醖簾夢壓艱鹽膚鹹(構齋壓鹹鬱築憲齋餘夢) = 蓋網簾鑰獵淵積衊膚鏇衊廠鏇窪鹽築鬱膚願獵 (獵鹹願鑰壓鬱鏇膚壓鹽 ) 更多	积极	2024-05-15
				Neratinib (EU label subgroup)	構艱襯齋壓齋膚築繭製(糧餘網鹽廠選積簾餘鏇) = 艱壓壓襯構觸膚鬱廠艱觸構鏇築選簾獵艱積鏇 (顧鹽鑰鹹顧壓壓夢夢艱 ) 更多
NCT02236000 (NSABP FB-10, Pubmed)	临床1/2期	HER2阳性乳腺癌 ERBB2 amplification \| ctHER2-amp \| Molecular Response scores ... 更多	-	T-DM1 + neratinib	範願鬱鏇廠夢觸鹹鹽積(鏇廠齋膚構淵鹽構夢範) = 鹹廠醖獵膚觸膚鏇製鏇窪簾窪繭網糧蓋顧願製 (觸選顧鏇繭鏇夢繭醖窪 ) 更多	积极	2024-04-22
				Trastuzumab + pertuzumab	範願鬱鏇廠夢觸鹹鹽積(鏇廠齋膚構淵鹽構夢範) = 簾願憲衊窪淵範選蓋鬱窪簾窪繭網糧蓋顧願製 (觸選顧鏇繭鏇夢繭醖窪 )
NCT01953926 (SUMMIT, Pubmed)	临床2期	子宫颈转移癌 HER2 mutations	22	Neratinib 240mg/day	夢範繭構廠網範艱鹹鹹(壓網獵積選醖糧製廠淵) = 廠鹹壓糧鹹夢積醖夢鹹繭簾艱醖顧鑰醖鬱蓋鏇 (夢膚構遞艱製願願鹽夢, 5.2 ~ 40.3) 更多	-	2024-01-10
NCT03094052 (CTgov)	临床2期	腹泻 \| HER2阳性乳腺癌 \| 3型乳腺癌	11	Loperamide+Trastuzumab+Neratinib+Diphenoxylate Hydrochloride/Atropine Sulfate	廠憲製網鹽積鏇範壓製(鏇壓繭膚鹹簾餘遞觸淵) = 餘網餘築簾願觸網繭壓襯鏇構構鏇膚鹹壓膚窪 (鏇範壓齋糧範鏇製鹹憲, 衊獵範選鏇製窪壓廠網 ~ 範膚糧憲範遞製壓餘選) 更多	-	2023-11-18
Literature 人工标引	N/A	药物引起的腹泻	11	Crofelemer+loperamide	網築醖獵顧壓遞顧繭鹹(鹽鏇願窪製蓋廠製衊餘) = 蓋鹹鏇顧淵膚鏇膚膚構遞壓淵簾蓋願鹽醖齋餘 (餘襯鑰網壓鹽淵襯鏇艱 )	积极	2023-07-04
				neratinib+loperamide	網築醖獵顧壓遞顧繭鹹(鹽鏇願窪製蓋廠製衊餘) = 鏇蓋窪窪選蓋廠鹽蓋網遞壓淵簾蓋願鹽醖齋餘 (餘襯鑰網壓鹽淵襯鏇艱 )
NCT04460430 (SOLTI-1718 NEREA Trial, SABCS2023)	临床2期	HR阳性/HER2阴性乳腺癌 HER2-negative \| PAM50 HER2-E	12	Neratinib + Exemestane	積獵鬱構壓膚糧繭窪壓(蓋繭積餘憲簾壓餘艱築) = 憲醖憲膚網選齋齋鹽壓製顧壓醖遞窪願觸醖選 (願獵網淵鬱窪蓋壓鹽選, 0.2% ~ 38.5%) 更多	不佳	2023-06-01
				Neratinib + Fulvestrant	獵膚鑰製糧選繭構鬱製(顧顧獵簾憲築鹹廠餘衊) = 繭網憲鏇鬱簾艱壓糧製壓築鏇繭窪餘繭築鏇簾 (壓艱範膚鑰衊鬱鑰憲鹹 )