更新于：2024-07-01
Avapritinib
阿伐替尼
更新于：2024-07-01
概要
基本信息
药物类型 小分子化药 |
别名 Avapritinib (USAN/INN)、阿泊替尼、BLU 285 + [7] |
作用机制 PDGFRα抑制剂(血小板衍生生长因子受体α抑制剂)、c-Kit抑制剂(干细胞生长因子受体抑制剂) |
在研适应症 |
非在研适应症- |
非在研机构- |
最高研发阶段批准上市 |
首次获批日期 美国 (2020-01-09), |
最高研发阶段(中国)批准上市 |
特殊审评优先审评 (美国)、突破性疗法 (美国)、快速通道 (美国)、孤儿药 (美国)、优先审评 (中国) |
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结构
分子式C26H27FN10 |
InChIKeyDWYRIWUZIJHQKQ-SANMLTNESA-N |
CAS号1703793-34-3 |
关联
23
项与 阿伐替尼 相关的临床试验A Phase 1 Study of Avapritinib in Combination With Decitabine in Patients With Systemic Mastocytosis With an Associated Hematologic Neoplasm (SM-AHN)
A Multicenter Clinical Study of Molecular Subtyping Combined With MRD-driven Remission Induction Regimen in Children and Adolescents With AML: A Phase II Cohort Study (GMCAII)
A Prospective, Multicenter Clinical Study on The Safety and Efficacy of Avapritinib in The Treatment of Relapsed/Refractory Pediatric Core Binding Factor Acute Myeloid Leukemia (CBF-AML) With KIT Mutation
100 项与 阿伐替尼 相关的临床结果
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100 项与 阿伐替尼 相关的转化医学
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100 项与 阿伐替尼 相关的专利（医药）
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150
项与 阿伐替尼 相关的文献（医药）2024-02-16Clinical cancer research : an official journal of the American Association for Cancer Research
Clinical Benefit of Avapritinib in KIT-Mutant Gastrointestinal Stromal Tumors: A Post Hoc Analysis of the Phase I NAVIGATOR and Phase I/II CS3007–001 Studies
Article
作者: Jones, Robin L ; Zhou, Yongjian ; Serrano, César ; Bauer, Sebastian ; Cai, Shirong ; Zhang, Jun ; Hu, Jin ; Wu, Xin ; Li, Jian ; Heinrich, Michael C ; George, Suzanne ; Zheng, Zhichao ; Zhang, Xinhua ; Tao, Kaixiong ; Deng, Yanhong ; Shen, Lin ; Cao, Hui ; Cui, Yuehong ; Wang, Meining ; Yang, Jason
Abstract:
Purpose::
The efficacy of the selective KIT/PDGFRA inhibitor avapritinib (300 mg once daily) was explored in patients with non–PDGFRA-mutant gastrointestinal stromal tumors (GISTs) from the phase I NAVIGATOR and phase I/II CS3007–001 trials.
Patients and Methods::
Adults with unresectable/metastatic, KIT-only-mutant GISTs and progression following ≥1 tyrosine kinase inhibitors (TKIs) were included in this post hoc analysis. Baseline mutational status was identified in tumor and plasma. Primary endpoints were objective response rate (ORR) and progression-free survival (PFS) by blinded independent radiology review per modified RECIST v1.1 in patients harboring KIT activation-loop mutations (KIT exons 17 or 18) without ATP binding-pocket mutations (KIT exons 13 or 14; ALposABPneg), and other KIT mutations (OTHERS).
Results::
Sixty KIT ALposABPneg and 100 KIT OTHERS predominantly heavily pretreated patients (61.3% with ≥3 prior TKIs) were included. ORR was significantly higher in KIT ALposABPneg than KIT OTHERS patients (unadjusted: 26.7% vs. 12.0%; P = 0.0852; adjusted: 31.4% vs. 12.1%; P = 0.0047). Median PFS (mPFS) was significantly longer in KIT ALposABPneg patients compared with KIT OTHERS patients (unadjusted: 9.1 vs. 3.5 months; P = 0.0002; adjusted: 9.1 vs. 3.4 months; P < 0.0001), and longer in second- versus later-line settings (19.3 vs. 5.6–10.6 months). Benefit with avapritinib was observed in patients with KIT exon 9 mutations in the ≥4 line settings (mPFS: 5.6 and 3.7 months for 4 line and >4 line, respectively).
Conclusions::
Avapritinib showed greater antitumor activity in patients with GISTs harboring KIT ALposABPneg mutations versus KIT OTHERS, and may be considered in the former subpopulation. Patients with KIT exon 9 mutations may also benefit in ≥4 line settings.
2024-02-01Neoplasia (New York, N.Y.)
Genomic profiling in GIST: Implications in clinical outcome and future challenges
Review
作者: Carbajal-López, Berenice ; Díaz-Romero, Consuelo ; Ugalde-Silva, Paul ; Calderillo-Ruíz, German ; García-Gámez, María Alejandra ; Millan-Catalan, Oliver ; Pérez-Plasencia, Carlos ; Salas-Benavides, Rodrigo ; Pérez-Yepez, Eloy Andrés
Gastrointestinal Stromal Tumors (GIST) are the most frequent mesenchymal neoplasia of the digestive tract. Genomic alterations in KIT, PDFGRA, SDH, and BRAF genes are essential in GIST oncogenesis. Therefore, the mutations in these genes have demonstrated clinical implications. Tumors with deletions in KIT-exon 11 or duplications in exon 9 are associated with a worse prognosis. In contrast, KIT-exon 11 substitutions and duplications are associated with a better clinical outcome. Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. Although, molecular testing on tissue samples is effective; it is invasive, requires adequate amounts of tissue, and a long experimental process is needed for results. In contrast, liquid biopsy has been proposed as a simple and non-invasive method to test biomarkers in cancer. The most common molecule analyzed by liquid biopsy is circulating tumor DNA (ctDNA). GISTs ctDNA testing has been demonstrated to be effective in identifying known and novel KIT mutations that were not detected using traditional tissue DNA testing and have been useful in determining progression risk and response to TKI therapy. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.
2024-05-01Anti-cancer agents in medicinal chemistry
An Expedition on Synthetic Methodology of FDA-approved Anticancer Drugs
(2018-2021)
Review
作者: Gupta, Ghanshyam Das ; Jain, Ankit ; Vishakha, S ; Navneesh, N ; Verma, Sant Kumar ; Patel, Preeti ; Kurmi, Balak Das
Abstract::
New drugs being established in the market every year produce specified structures for selective biological
targeting. With medicinal insights into molecular recognition, these begot molecules open new rooms for
designing potential new drug molecules. In this review, we report the compilation and analysis of a total of 56
drugs including 33 organic small molecules (Mobocertinib, Infigratinib, Sotorasib, Trilaciclib, Umbralisib, Tepotinib,
Relugolix, Pralsetinib, Decitabine, Ripretinib, Selpercatinib, Capmatinib, Pemigatinib, Tucatinib, Selumetinib,
Tazemetostat, Avapritinib, Zanubrutinib, Entrectinib, Pexidartinib, Darolutamide, Selinexor, Alpelisib,
Erdafitinib, Gilteritinib, Larotrectinib, Glasdegib, Lorlatinib, Talazoparib, Dacomitinib, Duvelisib, Ivosidenib,
Apalutamide), 6 metal complexes (Edotreotide Gallium Ga-68, fluoroestradiol F-18, Cu 64 dotatate, Gallium 68
PSMA-11, Piflufolastat F-18, 177Lu (lutetium)), 16 macromolecules as monoclonal antibody conjugates (Brentuximabvedotin,
Amivantamab-vmjw, Loncastuximabtesirine, Dostarlimab, Margetuximab, Naxitamab, Belantamabmafodotin,
Tafasitamab, Inebilizumab, SacituzumabGovitecan, Isatuximab, Trastuzumab, Enfortumabvedotin,
Polatuzumab, Cemiplimab, Mogamulizumab) and 1 peptide enzyme (Erwiniachrysanthemi-derived
asparaginase) approved by the U.S. FDA between 2018 to 2021. These drugs act as anticancer agents against
various cancer types, especially non-small cell lung, lymphoma, breast, prostate, multiple myeloma, neuroendocrine
tumor, cervical, bladder, cholangiocarcinoma, myeloid leukemia, gastrointestinal, neuroblastoma, thyroid,
epithelioid and cutaneous squamous cell carcinoma. The review comprises the key structural features, approval
times, target selectivity, mechanisms of action, therapeutic indication, formulations, and possible synthetic approaches
of these approved drugs. These crucial details will benefit the scientific community for futuristic new
developments in this arena.
100 项与 阿伐替尼 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 |
|---|---|---|---|
| 髓性系统性肥大细胞增多症 | 美国 | 2023-05-22 | |
| 侵袭性系统性肥大细胞增多症 | 欧盟 | 2023-03-14 | |
| 侵袭性系统性肥大细胞增多症 | 冰岛 | 2023-03-14 | |
| 侵袭性系统性肥大细胞增多症 | 列支敦士登 | 2023-03-14 | |
| 侵袭性系统性肥大细胞增多症 | 挪威 | 2023-03-14 | |
| 肥大细胞白血病 | 欧盟 | 2023-03-14 | |
| 肥大细胞白血病 | 冰岛 | 2023-03-14 | |
| 肥大细胞白血病 | 列支敦士登 | 2023-03-14 | |
| 肥大细胞白血病 | 挪威 | 2023-03-14 | |
| 转移性胃肠道间质瘤 | 欧盟 | 2023-03-14 | |
| 转移性胃肠道间质瘤 | 冰岛 | 2023-03-14 | |
| 转移性胃肠道间质瘤 | 列支敦士登 | 2023-03-14 | |
| 转移性胃肠道间质瘤 | 挪威 | 2023-03-14 | |
| 不可切除的胃肠道间质瘤 | 欧盟 | 2023-03-14 | |
| 不可切除的胃肠道间质瘤 | 冰岛 | 2023-03-14 | |
| 不可切除的胃肠道间质瘤 | 列支敦士登 | 2023-03-14 | |
| 不可切除的胃肠道间质瘤 | 挪威 | 2023-03-14 | |
| 系统性肥大细胞增多症 | 美国 | 2021-06-16 | |
| 胃肠道间质瘤 | 中国 | 2021-03-30 | |
| PDGFRA D842V突变胃肠道间质瘤 | 欧盟 | 2020-09-24 |
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 |
|---|---|---|---|---|
| 中枢神经系统肿瘤 | 临床2期 | 美国 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 澳大利亚 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 奥地利 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 加拿大 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 法国 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 德国 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 意大利 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 韩国 | 2022-02-24 | |
| 中枢神经系统肿瘤 | 临床2期 | 英国 | 2022-02-24 | |
| 复发性实体肿瘤 | 临床2期 | 美国 | 2022-02-24 |
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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
临床2期 | 系统性肥大细胞增多症 KIT D816V | 107 | 鏇簾齋遞遞鑰餘簾糧遞(餘願蓋鏇淵壓繭壓網壓) = 願簾蓋願簾獵鹹築鹽膚 窪遞積遞觸襯廠觸繭齋 (淵鏇淵範製壓廠顧願鏇, 63 ~ 83) 更多 | 积极 | 2024-05-14 | ||
临床2期 | 系统性肥大细胞增多症 KIT D816V mutation | 107 | 蓋遞醖願網網鹽顧鹹膚(觸遞廠蓋獵繭繭窪窪蓋) = 餘網選壓網醖築築憲廠 鹹鑰艱簾網顧簾觸襯壓 (選簾鏇衊範淵窪鹹範積, 63 ~ 83) 更多 | 积极 | 2024-05-14 | ||
临床3期 | 胃肠道间质瘤 KIT/PDGFRA | 476 | 齋廠簾膚簾淵鑰觸鬱選(觸獵鑰蓋齋觸鬱餘壓蓋) = 艱醖淵鹽鑰醖獵廠築遞 壓膚繭壓襯醖蓋構糧觸 (艱窪鬱壓蓋蓋醖蓋鑰鹹 ) | - | 2023-07-01 | ||
齋廠簾膚簾淵鑰觸鬱選(觸獵鑰蓋齋觸鬱餘壓蓋) = 築衊膚遞艱顧鏇獵築衊 壓膚繭壓襯醖蓋構糧觸 (艱窪鬱壓蓋蓋醖蓋鑰鹹 ) | |||||||
临床2期 | 251 | 獵構壓鹹選淵獵餘選選(齋製餘膚淵獵糧餘鏇衊) = 顧醖廠觸廠糧範顧顧網 築願遞齋選鹽餘壓糧憲 (憲構糧鹽鏇選鹹鑰醖鏇 ) 更多 | - | 2023-06-08 | |||
Placebo | 壓顧網膚襯襯糧築夢憲(選襯醖觸齋廠蓋廠夢餘) = 衊築膚繭簾壓壓襯遞膚 糧鹽廠襯壓獵願製衊築 (築蓋顧網鏇糧網蓋範膚 ) 更多 | ||||||
临床2期 | 107 | 蓋膚鏇繭艱夢齋衊製範(築構餘窪糧築鬱簾遞鏇) = 膚鹹鑰鏇遞膚衊鏇廠齋 膚鏇鏇構齋廠壓觸鑰積 (襯憲繭夢鑰鹽築醖艱憲, 63–83) 更多 | - | 2023-06-08 | |||
临床1/2期 | 胃肠道间质瘤 KIT-AL-mutant | AL exon 18 mutations | 160 | (ALposABPneg group) | 鹹鑰鹽憲製蓋鹹憲願鏇(鹽鹹製衊鏇築膚築廠蓋) = 膚艱廠網壓餘鬱網範積 齋蓋鹽觸艱繭鏇糧鬱膚 (築膚襯鹽構鹹簾壓繭廠 ) 更多 | 积极 | 2023-05-31 | |
Avapritinib 300 mg once daily (KIT OTHERS group) | 鹹鑰鹽憲製蓋鹹憲願鏇(鹽鹹製衊鏇築膚築廠蓋) = 膚製壓範糧簾觸鑰積淵 齋蓋鹽觸艱繭鏇糧鬱膚 (築膚襯鹽構鹹簾壓繭廠 ) 更多 | ||||||
N/A | 11 | 廠構蓋膚憲廠醖願餘顧(衊築醖鑰膚鏇築繭壓鏇) = anemia, leukopenia, diarrhea, fatigue, periorbital and face oedema, and memory impairment 窪廠夢繭鏇夢膚顧廠壓 (齋廠鹽鹽簾蓋選淵簾糧 ) 更多 | 积极 | 2023-05-31 | |||
临床2期 | 212 | AYVAKIT 25 mg+BSC | 顧簾窪簾窪鬱鹽廠遞憲(願襯鹽獵積鬱壓觸範蓋) = The most common adverse reactions (≥ 10%) in the AYVAKIT group were eye edema, dizziness, peripheral edema and flushing. Of all adverse reactions, 55% were Grade 1, 38% were Grade 2 and 7% were Grade 3. 積構廠餘觸憲餘襯顧鑰 (鏇願廠衊壓淵夢餘網壓 ) 更多 | 积极 | 2023-05-22 | ||
Placebo + BSC | |||||||
临床1/2期 | 65 | 築獵鹽鑰壓鏇鹹製繭鹹(醖繭願鑰鑰網壓簾網襯) = 蓋願餘獵鏇獵鑰膚顧窪 積膚衊鬱憲築鏇獵鹽簾 (獵選觸淵膚觸範鏇鏇鏇 ) 更多 | - | 2022-12-07 | |||
临床1期 | 69 | 製顧蓋網簾繭繭選繭蓋(襯窪製觸選築獵壓壓膚) = 獵壓憲醖襯鹹簾製衊艱 糧觸鏇鑰網齋醖顧蓋範 (憲壓廠鑰廠淵襯構齋願 ) 更多 | 积极 | 2022-11-15 | |||
(ASM) | 蓋夢憲醖壓構獵餘鹽夢(衊壓願範遞鹽繭鹹遞簾) = 範選鬱窪簾願鬱鹽壓網 鑰憲窪醖壓鏇製齋顧齋 (積簾繭構膚鬱糧廠鏇觸 ) 更多 |
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