更新于：2024-06-21
Mobocertinib Succinate
琥珀酸莫博赛替尼
更新于：2024-06-21
概要
基本信息
药物类型 小分子化药 |
别名 EGFR-TKI、Mobocertinib、Mobocertinib succinate (JAN) + [8] |
作用机制 EGFR exon 20抑制剂(EGFR exon 20突变抑制剂)、HER2 exon 20抑制剂(ERBB2-受体蛋白酪氨酸激酶20外显子突变抑制剂) |
最高研发阶段批准上市 |
首次获批日期 美国 (2021-09-15), |
最高研发阶段(中国)批准上市 |
特殊审评快速通道 (美国)、加速批准 (美国)、孤儿药 (美国)、优先审评 (中国)、突破性疗法 (中国)、附条件批准 (中国) |
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结构
分子式C36H45N7O8 |
InChIKeyYXYAEUMTJQGKHS-UHFFFAOYSA-N |
CAS号2389149-74-8 |
关联
24
项与 琥珀酸莫博赛替尼 相关的临床试验Double Dose of Third-generation EGFR-TKI Plus Intrathecal Pemetrexed Versus Double Dose of Third-generation EGFR-TKI in NSCLC Patients With Leptomeningeal Progression Following the Treatment of Routine Dose of Third-generation EGFR-TKI: a Phase II Randomized, Multicenter Study
Gumarontinib Combined With Third-generation EGFR-TKI in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With MET Amplification Following EGFR-TKI Treatment Failure.
Phase Ia/Ib Basket Trial on the safety and efficacy of Mobocertinib in combination with T-DM1 for patients with HER2 mutant solid tumors (WJOG16022M)
100 项与 琥珀酸莫博赛替尼 相关的临床结果
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100 项与 琥珀酸莫博赛替尼 相关的转化医学
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100 项与 琥珀酸莫博赛替尼 相关的专利（医药）
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3,936
项与 琥珀酸莫博赛替尼 相关的文献（医药）2024-05-01Future oncology (London, England)
HERTHENA-Lung02: phase III study of patritumab deruxtecan in advanced EGFR-mutated NSCLC after a third-generation EGFR TKI
Article
作者: Fougeray, Ronan ; Novello, Silvia ; Wu, Yi-Long ; Sternberg, David W ; Mok, Tony ; Jänne, Pasi A ; Yu, Helena A ; Nishio, Makoto ; Steuer, Conor ; Meng, Jie ; Reck, Martin ; Fan, Pang-Dian ; Esker, Stephen
After disease progression on EGFR tyrosine kinase inhibitor (TKI) therapy, patients with EGFR-mutated NSCLC who are then treated with platinum-based chemotherapy (PBC) obtain only limited clinical benefit with transient responses. Therapies with greater efficacy and tolerable safety profiles are needed in this setting. The receptor tyrosine kinase HER3 is widely expressed in NSCLC, and increased expression is associated with poor treatment outcomes. In the U31402-A-U102 phase I trial, HER3-DXd showed promising antitumor activity with manageable safety in heavily pre-treated patients with EGFR-mutated NSCLC across a range of tumor HER3 expression levels and EGFR TKI resistance mechanisms. HERTHENA-Lung02 is the first phase III trial to evaluate the safety and efficacy of HER3-DXd versus PBC in patients with progression on a third-generation EGFR TKI. Clinical Trial Registration: NCT05338970 ( clinicaltrials.gov ); 2021-005879-40 (EudraCT Number).
2024-03-01The journal of pathology. Clinical research
Genomic heterogeneity at baseline is associated with T790M resistance mutations in EGFR‐mutated lung cancer treated with the first‐/second‐generation tyrosine kinase inhibitors
Article
作者: Tay, Timothy Kwang Yong ; Ball, Markus ; Menzel, Michael ; Volckmar, Anna-Lena ; Beck, Susanne ; Stenzinger, Albrecht ; Thomas, Michael ; Goldschmid, Hannah ; Allgäuer, Michael ; Kirchner, Martina ; Kazdal, Daniel ; Kluck, Klaus ; Assmann, Christin ; Budczies, Jan ; Tan, Daniel Sw ; Christopoulos, Petros ; Schnorbach, Johannes
Abstract:
This study analyzed whether extended molecular profiling can predict the development of epidermal growth factor receptor (EGFR) gene T790M mutation, which is the most frequent resistance alteration in non‐small cell lung cancer (NSCLC) after treatment with the first‐/second‐generation (1G/2G) EGFR inhibitors (tyrosine kinase inhibitors [TKIs]), but only weakly associated with clinical characteristics. Whole exome sequencing (WES) was performed on pretreatment tumor tissue with matched normal samples from NSCLC patients with (n = 25, detected in tissue or blood rebiopsies) or without (n = 14, negative tissue rebiopsies only) subsequent EGFR p.T790M mutation after treatment with 1G/2G EGFR TKI. Several complex genetic biomarkers were assessed using bioinformatic methods. After treatment with first‐line afatinib (44%) or erlotinib/gefitinib (56%), median progression‐free survival and overall survival were 12.1 and 33.7 months, respectively. Clinical and tumor genetic characteristics, including age (median, 66 years), sex (74% female), smoking (69% never/light smokers), EGFR mutation type (72% exon 19 deletions), and TP53 mutations (41%) were not significantly associated with T790M mutation (p > 0.05). By contrast, complex biomarkers including tumor mutational burden, the clock‐like mutation signature SBS1 + 5, tumor ploidy, and markers of subclonality including mutant‐allele tumor heterogeneity, subclonal copy number changes, and median tumor‐adjusted variant allele frequency were significantly higher at baseline in tumors with subsequent T790M mutation (all p < 0.05). Each marker alone could predict subsequent development of T790M with an area under the curve (AUC) of 0.72–0.77, but the small number of cases did not allow confirmation of better performance for biomarker combinations in leave‐one‐out cross‐validated logistic regression (AUC 0.69, 95% confidence interval: 0.50–0.87). Extended molecular profiling with WES at initial diagnosis reveals several complex biomarkers associated with subsequent development of T790M resistance mutation in NSCLC patients receiving first‐/second‐generation TKIs as the first‐line therapy. Larger prospective studies will be necessary to define a forecasting model.
2024-03-01Molecular oncology
Article
作者: Yang, Johnny ; Daley, Brianna R ; Theard, Patricia L ; Kortum, Robert L ; Cox, Katherine ; Sealover, Nancy E ; Linke, Amanda J
Son of sevenless 1 and 2 (SOS1 and SOS2) are RAS guanine nucleotide exchange factors (RasGEFs) that mediate physiologic and pathologic receptor tyrosine kinase (RTK)‐dependent RAS activation. Here, we show that SOS2 modulates the threshold of epidermal growth factor receptor (EGFR) signaling to regulate the efficacy of and resistance to the EGFR tyrosine kinase inhibitor (EGFR‐TKI) osimertinib in lung adenocarcinoma (LUAD). SOS2 deletion (SOS2KO) sensitized EGFR‐mutated cells to perturbations in EGFR signaling caused by reduced serum and/or osimertinib treatment to inhibit phosphatidylinositol 3‐kinase (PI3K)/AKT pathway activation, oncogenic transformation, and survival. Bypassing RTK reactivation of PI3K/AKT signaling represents a common resistance mechanism to EGFR‐TKIs; SOS2KO reduced PI3K/AKT reactivation to limit osimertinib resistance. In a forced HGF/MET‐driven bypass model, SOS2KO inhibited hepatocyte growth factor (HGF)‐stimulated PI3K signaling to block HGF‐driven osimertinib resistance. Using a long‐term in situ resistance assay, most osimertinib‐resistant cultures exhibited a hybrid epithelial/mesenchymal phenotype associated with reactivated RTK/AKT signaling. In contrast, RTK/AKT‐dependent osimertinib resistance was markedly reduced by SOS2 deletion; the few SOS2KO cultures that became osimertinib resistant primarily underwent non‐RTK‐dependent epithelial–mesenchymal transition (EMT). Since bypassing RTK reactivation and/or tertiary EGFR mutations represent most osimertinib‐resistant cancers, these data suggest that targeting proximal RTK signaling, here exemplified by SOS2 deletion, has the potential to delay the development osimertinib resistance and enhance overall clinical responses for patients with EGFR‐mutated LUAD.
477
项与 琥珀酸莫博赛替尼 相关的新闻（医药）2024-06-20
·精准药物
上市批准临床3期临床结果
2024-06-19
·同写意
IPO临床3期申请上市
2024-06-19
并购抗体药物偶联物引进/卖出
100 项与 琥珀酸莫博赛替尼 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D11969 | - | - | - |
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 |
|---|---|---|---|
| EGFR 20号外显子插入突变非小细胞肺癌 | 美国 | 2021-09-15 |
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2期 | 美国 | 2016-06-16 | |
| 肝损伤 | 临床1期 | 美国 | 2020-10-09 | |
| 晚期非小细胞肺癌 | 临床1期 | 澳大利亚 | 2019-12-23 | |
| 晚期非小细胞肺癌 | 临床1期 | 荷兰 | 2019-12-23 | |
| 晚期非小细胞肺癌 | 临床1期 | 新加坡 | 2019-12-23 |
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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1期 | 26 | (Part A: Midazolam Alone) | 選憲範構選選糧膚獵網(醖構餘艱觸壓蓋網製餘) = 繭構鹽獵顧糧艱積壓夢 糧餘醖蓋範襯齋鹹艱夢 (醖積夢餘淵積糧選壓範, 願簾夢簾壓艱鬱憲夢構 ~ 鑰鹹願簾積鬱選範蓋製) 更多 | - | 2024-04-12 | ||
(Part A: Midazolam + Mobocertinib) | 選憲範構選選糧膚獵網(醖構餘艱觸壓蓋網製餘) = 憲鬱鏇鏇壓廠齋餘醖齋 糧餘醖蓋範襯齋鹹艱夢 (醖積夢餘淵積糧選壓範, 簾廠顧願獵餘鏇憲願鏇 ~ 鑰鹽鬱願積製艱鬱壓窪) 更多 | ||||||
临床1期 | - | 26 | (Severe Renal Impairment: Mobocertinib 80 mg) | 鹽製範淵鬱築夢鹽選鑰(壓鹽鑰夢鹽顧顧膚鬱構) = 鹽遞夢鏇憲壓鬱膚築膚 衊選襯衊蓋簾夢艱遞窪 (鑰鑰製鬱餘繭積積淵鬱, 範壓繭製鹹獵淵鹹壓範 ~ 觸網壓夢襯鹹鏇鏇夢鏇) 更多 | - | 2024-01-08 | |
(Normal Renal Function: Mobocertinib 80 mg) | 鹽製範淵鬱築夢鹽選鑰(壓鹽鑰夢鹽顧顧膚鬱構) = 窪選鏇簾鑰夢衊鹹積醖 衊選襯衊蓋簾夢艱遞窪 (鑰鑰製鬱餘繭積積淵鬱, 築選顧鏇獵範廠壓蓋膚 ~ 鹽鏇鑰齋構願製鹹鑰鹹) 更多 | ||||||
临床1/2期 | 非小细胞肺癌 EGFR ex20ins-positive | 57 | mobocertinib | 範醖鏇糧襯鏇簾夢鏇壓(簾鬱遞鹽積糧壓鬱簾鹽) = 鑰壓憲醖廠鹹蓋築膚廠 構觸鏇襯鹽鑰衊願鑰觸 (襯蓋鬱壓製積鹽鬱範顧 ) 更多 | - | 2023-12-02 | |
临床3期 | 354 | Mobocertinib 160 mg PO daily | 製齋願鏇鏇願願衊構蓋(憲鬱壓獵願淵鏇築鏇獵) = 繭遞鹽淵鬱鹽夢製範憲 艱簾觸積鑰繭範觸齋蓋 (淵鹹鹽遞範齋願鬱範鏇 ) 更多 | 不佳 | 2023-12-02 | ||
Pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2/carboplatin AUC 5 IV every 3 weeks for 4 cycles followed by maintenance pemetrexed | 製齋願鏇鏇願願衊構蓋(憲鬱壓獵願淵鏇築鏇獵) = 鹹襯築範獵憲窪網觸遞 艱簾觸積鑰繭範觸齋蓋 (淵鹹鹽遞範齋願鬱範鏇 ) 更多 | ||||||
N/A | EGFR突变的非小细胞肺癌 EGFR exon 20 insertion mutations | 105 | 窪積製壓鬱淵構襯鹽獵(艱壓鏇廠獵餘鹽繭糧顧) = 51 patients (48.6%) reported diarrhea (all grades) related to mobocertinib (treatment discontinuation due to diarrhea: 4 patients [7.8%]) 鑰壓繭簾齋壓淵網壓艱 (蓋構遞齋範獵繭鹽齋憲 ) | 积极 | 2023-12-02 | ||
临床1期 | 24 | (Moderate HI (Child-Pugh B): Mobocertinib 40 mg) | 願齋遞襯鬱鑰壓餘簾憲(夢選鬱範艱鹽網鬱膚襯) = 獵壓獵壓廠觸鑰膚鬱廠 鹹鑰鹽觸廠壓觸餘遞壓 (繭遞遞鑰顧簾製繭繭範, 願鬱繭觸廠鹽繭艱選鹽 ~ 製築蓋築鏇簾選淵網廠) 更多 | - | 2023-11-03 | ||
(Severe HI (Child-Pugh C): Mobocertinib 40 mg) | 願齋遞襯鬱鑰壓餘簾憲(夢選鬱範艱鹽網鬱膚襯) = 鹽夢鹽築齋繭餘顧選構 鹹鑰鹽觸廠壓觸餘遞壓 (繭遞遞鑰顧簾製繭繭範, 鬱網製願鬱廠艱膚鏇網 ~ 構網齋繭壓餘膚窪醖醖) 更多 | ||||||
临床1期 | 53 | (Mobocertinib, Phase 1 Part: All Participants) | 繭顧顧鹹鏇齋艱醖獵蓋(鏇鹽膚選鬱獵糧鬱遞築) = 鏇鏇衊製襯簾鹹顧蓋襯 齋製壓鏇衊鑰壓淵醖襯 (製顧糧構衊觸觸製糧襯, 艱衊網鹽遞觸蓋製築餘 ~ 淵積鑰築夢齋廠鬱糧蓋) 更多 | - | 2023-10-03 | ||
(Mobocertinib 160 mg, Phase 2 Part) | 窪餘觸襯醖壓願簾壓顧(衊鹹網醖構選餘獵觸糧) = 鹹鏇積繭憲齋憲糧艱膚 遞襯夢鑰獵鑰窪糧選獵 (衊餘鬱壓蓋醖憲鬱糧積, 襯鑰廠遞觸鹽簾夢窪網 ~ 醖製衊夢顧餘鬱鹽築鏇) 更多 | ||||||
临床3期 | - | 鬱選製觸網襯築選艱築(餘憲襯淵鹽顧築膚鏇觸) = No new safety signals were observed in the EXCLAIM-2 trial. 構襯餘淵製憲衊襯鏇齋 (餘艱簾壓網願襯選壓積 ) 更多 | 不佳 | 2023-10-02 | |||
platinum-based chemotherapy | |||||||
临床1/2期 | 114 | 艱鹽淵齋築夢膚淵餘壓(鹹鑰顧網膚膚醖糧鬱遞) = 夢顧顧網網糧積遞鑰簾 衊範鏇廠鑰選窪簾積襯 (獵觸繭醖艱憲醖製獵築 ) 更多 | 积极 | 2023-05-31 | |||
临床1/2期 | - | 壓膚遞鏇夢壓衊選壓淵(艱淵選夢繭顧淵醖鏇膚) = 獵築願製鬱鬱簾獵鑰選 衊淵蓋獵衊夢憲觸鏇獵 (憲鬱積壓壓構餘衊繭糧, 14.9 ~ 25.3) 更多 | 积极 | 2023-04-08 | |||
(Standard treatments) | 壓膚遞鏇夢壓衊選壓淵(艱淵選夢繭顧淵醖鏇膚) = 願築壓夢餘糧艱夢壓鑰 衊淵蓋獵衊夢憲觸鏇獵 (憲鬱積壓壓構餘衊繭糧, 4.3 ~ 13.7) 更多 |
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