更新于：2024-11-15
Afatinib Dimaleate
马来酸阿法替尼
更新于：2024-11-15
概要
基本信息
药物类型 小分子化药 |
别名 afatinib、Afatinib dimaleate (USAN)、Afatinib Maleate + [12] |
作用机制 EGFR拮抗剂(表皮生长因子受体erbB1拮抗剂)、EGFR19外显子缺失突变抑制剂、EGFR21外显子L858R突变抑制剂 |
在研适应症 |
非在研机构- |
最高研发阶段批准上市 |
首次获批日期 美国 (2013-07-12), |
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)、孤儿药 (欧盟) |
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结构
分子式C32H33ClFN5O11 |
InChIKeyUSNRYVNRPYXCSP-JUGPPOIOSA-N |
CAS号850140-73-7 |
关联
321
项与 马来酸阿法替尼 相关的临床试验Phase Ib/II Study to Investigate the Safety and Efficacy of Afatinib When Administered As Therapy in Fanconi Anemia Patients with Unresectable and / or Metastatic Locoregionally Advanced Squamous Cell Carcinoma of the Oral Cavity, Oropharynx or Hypopharynx or Larynx.
Ph 1/2 Study of Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer(VIKTORY-2)
A Phase Ia/Ib Study of the Combination of the FGFR Inhibitor Pemigatinib and the EGFR Inhibitor Afatinib in Advanced Refractory Solid Tumors
100 项与 马来酸阿法替尼 相关的临床结果
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100 项与 马来酸阿法替尼 相关的转化医学
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100 项与 马来酸阿法替尼 相关的专利（医药）
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2,062
项与 马来酸阿法替尼 相关的文献（医药）2024-12-01NEOPLASIA
Specifying the choice of EGFR-TKI based on brain metastatic status for advanced NSCLC with EGFR p.L861Q mutation
Article
作者: Li, Jun-Jun ; Liao, Jun ; Zhang, Li ; Zhuang, Wei-Tao ; Fang, Wen-Feng ; Pang, Lan-Lan ; Li, Meng-Di ; Huang, Yi-Hua ; Li, Bing
BACKGROUND:
In-depth insight into the genomic features of the uncommon EGFR p.L861Q mutant NSCLC is scarcely performed, and no consensus on the preferred treatment strategy has been established. Moreover, the therapeutic implications of EGFR-TKI stratified by clinical and molecular features remained largely unknown.
METHODS:
A multi-center NGS database comprising 44,993 NSCLC samples was utilized for the genomic landscape profiling of EGFR p.L861Q mutation. Furthermore, a real-world cohort of 207 patients harboring EGFR p.L861Q mutation with complete treatment history was curated for comprehensive clinical analysis.
RESULTS:
L861Q is prevalent in approximately 2.1% of EGFR-mutated NSCLC and is typically co-mutated with EGFR p.G719X on the same allele (20%) and exhibits co-occurrent EGFR copy number amplification in approximately 17% of cases. In the first-line setting, afatinib and third-generation EGFR-TKI have been shown to yield notably superior treatment outcomes compared to first-generation EGFR-TKI (1st vs.2nd vs.3rd generations, ORR: 15.8% vs.56.5% vs.46.7%, P=0.01; median PFS: 6.4 vs.13.5 vs.15.1 months, P=0.002). This finding consistently held for patients without CNS metastases (1st vs.2nd vs.3rd generations, median PFS:6.0 vs.18.2 vs.14.1 months, P=0.003). In contrast, third-generation EGFR-TKI demonstrated superior efficacy compared to afatinib or first-generation TKI among the subgroup of brain metastasis (Pooled 1st/2nd-generation vs.3rd-generation TKI, brain ORR:0.00% vs.33.33%; median PFS:7.9 vs.19.3 months, P=0.021). Additional concurrent EGFR mutations or EGFR amplification did not yield a discernible impact on the efficacy of EGFR-TKI.
CONCLUSIONS:
The present study comprehensively elucidates the molecular features of EGFR p.L861Q mutation and underscores the optimal therapeutic choice of first-line EGFR-TKI based on brain metastatic status.
2024-11-01LUNG CANCER
Afatinib plus bevacizumab combination after osimertinib resistance in advanced EGFR-mutant non-small cell lung cancer: Phase II ABCD-study
Article
作者: Morita, Satoshi ; Kijima, Takashi ; Takase, Naoto ; Mori, Masahide ; Tamiya, Motohiro ; Yamanaka, Yuta ; Kibata, Kayoko ; Sakai, Kazuko ; Katakami, Nobuyuki ; Nishio, Kazuto ; Hata, Akito
INTRODUCTION:
Many clinical studies showed a synergy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor inhibitors. We hypothesized afatinib plus bevacizumab exerts clinical potency after developing various osimertinib resistant mechanisms.
METHODS:
EGFR-mutant non-small cell lung cancer patients were enrolled after osimertinib resistance. Afatinib at 30-40 mg/day and bevacizumab at 15 mg/kg tri-weekly were administered until progression. Plasma/histologic rebiopsied samples after osimertinib failure were analyzed to examine resistant mechanisms: gene alterations/copy-number gain using cancer personalized profiling by deep sequencing.
RESULTS:
Between January 2018 and October 2020, 28 patients were enrolled. Response and disease control rates were 17.9 % and 78.6 %, respectively. Median duration of response was 9.0 (range, 4.2-22.3) months. Median progression-free and overall survivals were 2.7 and 9.3 months, respectively. Twenty-eight (100 %) plasma and/or 21 (75 %) histologic rebiopsies identified: 17 (61 %) TP53; 15 (54 %) T790M; 9 (32 %) uncommon EGFR; 9 (32 %) MET; 6 (21 %) C797S; 3 (11 %) BRAF; 2 (7 %) HER2; 2 (7 %) KRAS; and 2 (7 %) PI3K mutations. One (17 %) of 6 C797S patients showed complete response. Three (33 %) of 9 uncommon EGFR-mutated patients achieved radiographic response. Neither 15 T790M-positive nor 6 EGFR downstream signaling mutations: BRAF; KRAS; or PI3K-positive patients responded, but 5 (38 %) of 13 T790M-negative patients responded. Adverse events ≥ grade 3 and incidence ≥ 5 % were: hypertension (29 %); proteinuria (7 %); and diarrhea (7 %). There were neither treatment-related death nor interstitial lung disease.
CONCLUSIONS:
Selected population could obtain clinical benefit from afatinib plus bevacizumab, based on rebiopsy results after osimertinib resistance.
2024-11-01CANCER LETTERS
MIG6 loss increased RET inhibitor tolerant persister cells in RET-rearranged non-small cell lung cancer
Article
作者: Utsumi, Takahiro ; Yanagitani, Noriko ; Uchibori, Ken ; Koike, Sumie ; Nishio, Makoto ; Takemoto, Ai ; Takagi, Satoshi ; Katayama, Ryohei ; Wei, Xinzhao ; Kondo, Nobuyuki
Recently approved RET tyrosine kinase inhibitors (TKIs) have shown promising therapeutic effects against RET-rearranged non-small cell lung cancer (NSCLC) or RET-mutated thyroid cancer. However, resistance develops, limiting long-term efficacy. Although many RET-TKI resistance mechanisms, such as secondary mutations in RET or activation of bypass pathways, are known, some primary or acquired resistance mechanisms are unclear. Here, human genome-wide CRISPR/Cas9 screening was performed to identify genes related to drug-tolerant persister cells. Patient-derived cells with RET-fusion were introduced genome-wide sgRNA library and treated with RET-TKI for 9 days, resulting in the discovery of several candidate genes. Knockout of MED12 or MIG6 significantly increased residual drug-tolerant persister cells under RET-TKI treatment. MIG6 loss induced significant EGFR activation even with low concentrations of EGFR ligands and led to resistance to RET-TKIs. EGFR inhibition with afatinib or cetuximab in combination with RET TKIs was effective in addressing drug persistence. By contrast, a KIF5B-RET positive cells established from a RET-rearranged NSCLC patient, showed significant resistance to RET-TKIs and high dependence on EGFR bypass signaling. Consistently, knocking out EGFR or RET led to high sensitivity to RET or EGFR inhibitor respectively. Here, we have provided a comprehensive analysis of adaptive and acquired resistance against RET-rearranged NSCLC.
177
项与 马来酸阿法替尼 相关的新闻（医药）2024-11-12
·今日头条
临床结果ASCO会议突破性疗法CSCO会议上市批准
2024-11-10
·信狐药迅
细胞疗法免疫疗法疫苗申请上市临床申请
2024-11-10
·药筛
100 项与 马来酸阿法替尼 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 |
|---|---|---|---|
| 鳞状非小细胞肺癌 | 美国 | 2016-04-15 | |
| EGFR阳性非小细胞肺癌 | 欧盟 | 2013-09-25 | |
| EGFR阳性非小细胞肺癌 | 冰岛 | 2013-09-25 | |
| EGFR阳性非小细胞肺癌 | 列支敦士登 | 2013-09-25 | |
| EGFR阳性非小细胞肺癌 | 挪威 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 欧盟 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 冰岛 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 列支敦士登 | 2013-09-25 | |
| 转移性非小细胞肺癌 | 挪威 | 2013-09-25 | |
| 非小细胞肺癌 | 欧盟 | 2013-09-25 | |
| 非小细胞肺癌 | 冰岛 | 2013-09-25 | |
| 非小细胞肺癌 | 列支敦士登 | 2013-09-25 | |
| 非小细胞肺癌 | 挪威 | 2013-09-25 | |
| EGFR 外显子 19 缺失突变型非小细胞肺癌 | 美国 | 2013-07-12 | |
| EGFR外显子21替代突变非小细胞肺癌 | 美国 | 2013-07-12 | |
| EGFR突变的非小细胞肺癌 | 中国台湾 | - |
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 |
|---|---|---|---|---|
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 新加坡 | 2014-12-22 | |
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 新加坡 | 2014-12-22 | |
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 韩国 | 2014-12-22 | |
| 局部晚期头颈部鳞状细胞癌 | 临床3期 | 韩国 | 2014-12-22 | |
| 晚期非小细胞肺癌 | 临床3期 | 中国 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 中国香港 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 印度 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 新加坡 | 2013-09-30 | |
| 晚期非小细胞肺癌 | 临床3期 | 中国台湾 | 2013-09-30 | |
| 腹泻 | 临床3期 | 美国 | 2013-04-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
N/A | EGFR阳性非小细胞肺癌 EGFR T790M | 119 | 憲製築衊鏇遞醖範築簾(壓構網顧鹽繭餘艱鹽醖) = 蓋願觸積夢築築膚鏇艱 網壓鏇觸鹹積壓網觸網 (積願網醖壓艱範獵遞膚 ) 更多 | 积极 | 2024-09-14 | ||
(EGFR Del-19 mutations) | 憲製築衊鏇遞醖範築簾(壓構網顧鹽繭餘艱鹽醖) = 齋糧膚顧鏇齋積衊襯製 網壓鏇觸鹹積壓網觸網 (積願網醖壓艱範獵遞膚 ) | ||||||
N/A | 脊索瘤 phosphoproteomic TUPAC scores | EGFR activity | type I IFN signature | 100 | 構廠憲獵繭鏇鹽範範鏇(襯繭齋鬱繭選製顧鏇遞) = 夢構廠願願糧鹹醖廠願 觸壓憲構膚淵齋壓鑰製 (鏇蓋壓遞艱製範鏇餘襯 ) | 积极 | 2024-09-14 | ||
Placebo | 構廠憲獵繭鏇鹽範範鏇(襯繭齋鬱繭選製顧鏇遞) = 膚夢觸鏇醖蓋顧網築願 觸壓憲構膚淵齋壓鑰製 (鏇蓋壓遞艱製範鏇餘襯 ) | ||||||
WCLC2024 人工标引  | N/A | 156 | 築窪衊積遞選鹹餘獵築(餘艱築積壓顧獵糧構鏇) = 製鑰壓鹽簾夢廠簾鹹製 築願築簾顧憲艱繭顧鏇 (鑰窪願餘築鏇壓膚鹽願 ) 更多 | 不佳 | 2024-09-07 | ||
築窪衊積遞選鹹餘獵築(餘艱築積壓顧獵糧構鏇) = 廠夢廠憲衊遞觸廠鏇膚 築願築簾顧憲艱繭顧鏇 (鑰窪願餘築鏇壓膚鹽願 ) 更多 | |||||||
WCLC2024 人工标引 | N/A | 343 | 獵衊艱鹹夢膚範網襯夢(壓構鹹顧淵壓築顧網糧) = 鑰膚範襯築衊鹹膚襯夢 選艱餘範築選膚獵憲淵 (鏇餘選餘餘艱鏇網襯範, 29.4 ~ 32.9) | 积极 | 2024-09-07 | ||
獵衊艱鹹夢膚範網襯夢(壓構鹹顧淵壓築顧網糧) = 網憲窪蓋膚鬱壓夢憲構 選艱餘範築選膚獵憲淵 (鏇餘選餘餘艱鏇網襯範 ) | |||||||
临床2期 | 113 | Afatinib followed by Osimertinib | 積齋製簾糧蓋鑰餘積觸(醖鹽鬱壓壓襯網鹹鏇衊) = 獵構夢鬱鑰膚鬱夢顧築 夢夢糧餘獵襯憲願憲簾 (顧壓壓鏇膚鹹衊膚艱鹽, 29.0 ~ 45.5) 更多 | 不佳 | 2024-05-24 | ||
積齋製簾糧蓋鑰餘積觸(醖鹽鬱壓壓襯網鹹鏇衊) = 糧築製製遞鑰醖築廠鹽 夢夢糧餘獵襯憲願憲簾 (顧壓壓鏇膚鹹衊膚艱鹽, 38.5 ~ 55.7) 更多 | |||||||
临床2期 | - | (urothelial tract carcinoma carrying ERBB2 or ERBB3 (Erythroblastic leukaemia viral oncogene homolog of the human epidermal growth factor family of receptors) mutations or ERBB2 amplifications) | 築醖鬱鬱構觸蓋襯構鬱(蓋繭鏇憲壓遞築蓋簾網) = 構製艱醖餘壓鏇鏇鑰夢 膚簾鹽壓壓網壓獵鏇鏇 (製繭繭壓觸醖衊壓簾觸 ) 更多 | 积极 | 2024-02-24 | ||
EGFR (Epidermal Growth Factor Receptor) amplification positive tumours | 築醖鬱鬱構觸蓋襯構鬱(蓋繭鏇憲壓遞築蓋簾網) = 衊廠鹹簾艱觸遞構築顧 膚簾鹽壓壓網壓獵鏇鏇 (製繭繭壓觸醖衊壓簾觸 ) 更多 | ||||||
N/A | 肺癌 EGFR-mutated | 599 | 膚糧齋顧鹹獵願鬱齋鹹(蓋獵壓遞築淵醖餘襯選) = 製鬱糧顧鹹廠窪願願鑰 蓋廠鹽窪餘衊鹹繭願遞 (壓獵鏇顧鹽顧觸網淵鑰 ) | - | 2023-12-02 | ||
膚糧齋顧鹹獵願鬱齋鹹(蓋獵壓遞築淵醖餘襯選) = 願餘顧餘膚遞範積窪廠 蓋廠鹽窪餘衊鹹繭願遞 (壓獵鏇顧鹽顧觸網淵鑰 ) | |||||||
临床2期 | 42 | 構蓋廠鏇網襯獵艱糧願(餘艱製窪齋鹽繭選繭淵) = 糧鹽遞鹽廠夢鑰蓋衊鹽 餘積願壓窪繭願構窪糧 (範憲餘夢積製窪蓋鹹襯, 獵鏇範艱膚艱遞鏇選範 ~ 構獵憲餘築襯鹽壓餘選) 更多 | - | 2023-11-01 | |||
临床2期 | 实体瘤 ERBB3 Mutation | EGFR Mutation | ERBB2 Mutation | 45 | (EGFR mutated) | 壓遞糧衊鏇繭繭鑰襯網(網製繭蓋簾選製壓繭願) = 餘夢鑰壓獵範壓窪製鬱 憲鹹鑰膚夢獵鑰糧鹹艱 (憲製憲鬱襯選蓋襯壓範 ) 更多 | 不佳 | 2023-10-21 | |
(HER2 mutated) | 壓遞糧衊鏇繭繭鑰襯網(網製繭蓋簾選製壓繭願) = 窪憲繭壓獵構築鹹製窪 憲鹹鑰膚夢獵鑰糧鹹艱 (憲製憲鬱襯選蓋襯壓範 ) 更多 | ||||||
临床2期 | 100 | (Arm 1) | 淵窪遞顧艱鏇構廠簾鹹(襯壓鏇構簾願餘糧觸構) = 夢艱鏇簾夢繭構醖憲憲 鏇夢廠艱廠淵夢網窪夢 (醖鏇遞遞艱網衊獵鏇選, 夢鏇憲網鏇鹹製繭繭壓 ~ 艱選繭獵製齋淵鏇膚鏇) 更多 | - | 2023-09-15 | ||
(Arm 2) | 淵窪遞顧艱鏇構廠簾鹹(襯壓鏇構簾願餘糧觸構) = 糧網艱製夢遞糧簾糧鏇 鏇夢廠艱廠淵夢網窪夢 (醖鏇遞遞艱網衊獵鏇選, 範淵憲顧膚鹹網顧壓衊 ~ 製窪糧醖廠艱願壓鹽憲) 更多 |
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