更新于：2024-06-24
Tolebrutinib
更新于：2024-06-24
概要
基本信息
药物类型 小分子化药 |
别名 BTKI'168、BTKI('168)、PRN-2246 + [2] |
靶点 |
作用机制 BTK抑制剂(酪氨酸蛋白激酶BTK抑制剂) |
非在研适应症 |
非在研机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)临床3期 |
特殊审评- |
结构
分子式C26H25N5O3 |
InChIKeyKOEUOFPEZFUWRF-LJQANCHMSA-N |
CAS号1971920-73-6 |
关联
31
项与 Tolebrutinib 相关的临床试验An Interventional, Phase 3 Extension Study to Investigate Long-term Safety and Tolerability of Tolebrutinib in Participants With Relapsing Multiple Sclerosis, Primary Progressive Multiple Sclerosis, or Nonrelapsing Secondary Progressive Multiple Sclerosis
一项在成人全身型重症肌无力受试者中评价tolebrutinib（SAR442168）的有效性和安全性的III 期、随机、双盲、安慰剂对照、平行组研究
An Open-label, Multi-center Phase 1 Pharmacokinetic and Tolerability Study of Tolebrutinib Given as a Single Oral Dose in Participants With Renal Impairment and in Matched Participants With Normal Renal Function
100 项与 Tolebrutinib 相关的临床结果
登录后查看更多信息
100 项与 Tolebrutinib 相关的转化医学
登录后查看更多信息
100 项与 Tolebrutinib 相关的专利（医药）
登录后查看更多信息
231
项与 Tolebrutinib 相关的文献（医药）2024-04-01Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Lisocabtagene Maraleucel in Relapsed/Refractory Mantle Cell Lymphoma: Primary Analysis of the Mantle Cell Lymphoma Cohort From TRANSCEND NHL 001, a Phase I Multicenter Seamless Design Study
Article
作者: Palomba, M Lia ; Kostic, Ana ; Andreadis, Charalambos ; Abramson, Jeremy S ; Wang, Michael ; Peng, Lily ; Ghosh, Nilanjan ; Gordon, Leo I ; Lunning, Matthew ; Hirayama, Alexandre V ; Espinola, Ricardo ; Arnason, Jon ; Dehner, Christine ; Kamdar, Manali ; Chattin, Amy ; Ogasawara, Ken ; Solomon, Scott R ; Siddiqi, Tanya ; Mehta, Amitkumar ; Eliason, Laurie
PURPOSE:
To report the primary analysis results from the mantle cell lymphoma (MCL) cohort of the phase I seamless design TRANSCEND NHL 001 (ClinicalTrials.gov identifier: NCT02631044 ) study.
METHODS:
Patients with relapsed/refractory (R/R) MCL after ≥two lines of previous therapy, including a Bruton tyrosine kinase inhibitor (BTKi), an alkylating agent, and a CD20-targeted agent, received lisocabtagene maraleucel (liso-cel) at a target dose level (DL) of 50 × 106 (DL1) or 100 × 106 (DL2) chimeric antigen receptor-positive T cells. Primary end points were adverse events (AEs), dose-limiting toxicities, and objective response rate (ORR) by independent review committee per Lugano criteria.
RESULTS:
Of 104 leukapheresed patients, liso-cel was infused into 88. Median (range) number of previous lines of therapy was three (1-11) with 30% receiving ≥five previous lines of therapy, 73% of patients were age 65 years and older, 69% had refractory disease, 53% had BTKi refractory disease, 23% had TP53 mutation, and 8% had secondary CNS lymphoma. Median (range) on-study follow-up was 16.1 months (0.4-60.5). In the efficacy set (n = 83; DL1 + DL2), ORR was 83.1% (95% CI, 73.3 to 90.5) and complete response (CR) rate was 72.3% (95% CI, 61.4 to 81.6). Median duration of response was 15.7 months (95% CI, 6.2 to 24.0) and progression-free survival was 15.3 months (95% CI, 6.6 to 24.9). Most common grade ≥3 treatment-emergent AEs were neutropenia (56%), anemia (37.5%), and thrombocytopenia (25%). Cytokine release syndrome (CRS) was reported in 61% of patients (grade 3/4, 1%; grade 5, 0), neurologic events (NEs) in 31% (grade 3/4, 9%; grade 5, 0), grade ≥3 infections in 15%, and prolonged cytopenia in 40%.
CONCLUSION:
Liso-cel demonstrated high CR rate and deep, durable responses with low incidence of grade ≥3 CRS, NE, and infections in patients with heavily pretreated R/R MCL, including those with high-risk, aggressive disease.
2024-03-01Blood reviews
Richter's transformation: Transforming the clinical landscape
Review
作者: Munir, T ; Eyre, T A ; Barrett, A ; Appleby, N ; Dreau, H ; Fox, C P
Richter transformation (RT) represents an aggressive histological transformation from chronic lymphocytic leukaemia, most often to a large B cell lymphoma. It is characterised by chemo-resistance and subsequent short survival. Drug development has struggled over recent years in light of the aggressive kinetics of the disease, lack of pivotal registrational trials and relative rarity of the phenomenon. In this review we will highlight the diagnostic and therapeutic challenges of managing patients with RT as well as taking a look to the future therapeutic landscape. Highly active therapies developed across B cell malignancies are starting to impact this field, with T-cell activation therapies (CAR-T, bispecific antibodies), antibody-drug conjugates, and novel small molecule inhibitor combinations (e.g. BTKi-BCL2i) being actively studied. We will highlight the data supporting these developments and look to the studies to come to provide hope for patients suffering from this devastating disease.
2024-02-22Blood
CAR T cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: the phase 2 TARMAC study
Article
作者: Tam, Constantine ; Seymour, John F ; Westerman, David ; Koldej, Rachel ; Cheah, Chan Y ; Morgan, Huw ; Khot, Amit ; Holzwart, Nicholas ; Sabahi, Zahra ; Caldwell, Imogen ; Blombery, Piers ; Xie, Jing ; Ryland, Georgina ; Dickinson, Michael ; Minson, Adrian ; Anderson, Mary Ann ; Saghebi, Javad ; Ritchie, David ; Hamad, Nada ; Robertson, Molly ; Lade, Stephen
Abstract:
CD19-directed chimeric antigen receptor T cells (CAR-T) achieve high response rates in patients with relapsed/refractory mantle cell lymphoma (MCL). However, their use is associated with significant toxicity, relapse concern, and unclear broad tractability. Preclinical and clinical data support a beneficial synergistic effect of ibrutinib on apheresis product fitness, CAR-T expansion, and toxicity. We evaluated the combination of time-limited ibrutinib and CTL019 CAR-T in 20 patients with MCL in the phase 2 TARMAC study. Ibrutinib commenced before leukapheresis and continued through CAR-T manufacture for a minimum of 6 months after CAR-T administration. The median prior lines of therapy was 2; 50% of patients were previously exposed to a Bruton tyrosine kinase inhibitor (BTKi). The primary end point was 4-month postinfusion complete response (CR) rate, and secondary end points included safety and subgroup analysis based on TP53 aberrancy. The primary end point was met; 80% of patients demonstrated CR, with 70% and 40% demonstrating measurable residual disease negativity by flow cytometry and molecular methods, respectively. At 13-month median follow-up, the estimated 12-month progression-free survival was 75% and overall survival 100%. Fifteen patients (75%) developed cytokine release syndrome; 12 (55%) with grade 1 to 2 and 3 (20%) with grade 3. Reversible grade 1 to 2 neurotoxicity was observed in 2 patients (10%). Efficacy was preserved irrespective of prior BTKi exposure or TP53 mutation. Deep responses correlated with robust CAR-T expansion and a less exhausted baseline T-cell phenotype. Overall, the safety and efficacy of the combination of BTKi and T-cell redirecting immunotherapy appears promising and merits further exploration. This trial was registered at www.ClinicalTrials.gov as #NCT04234061.
219
项与 Tolebrutinib 相关的新闻（医药）2024-06-23
·药明康德
细胞疗法临床结果免疫疗法临床2期
2024-06-22
·药明康德
基因疗法细胞疗法上市批准临床结果临床1期
2024-06-18
·药明康德
细胞疗法临床结果免疫疗法ASH会议
100 项与 Tolebrutinib 相关的药物交易
登录后查看更多信息
研发状态
10 条进展最快的记录, 后查看更多信息
登录
| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 重症肌无力 | 临床3期 | 巴西 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 巴西 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 加拿大 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 加拿大 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 德国 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 德国 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 匈牙利 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 匈牙利 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 意大利 | 2021-12-03 | |
| 重症肌无力 | 临床3期 | 意大利 | 2021-12-03 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床3期 | 6 | placebo+tolebrutinib (DB Period: Placebo) | 糧糧夢襯積襯廠網網顧(鹽鏇觸餘鬱顧顧糧積願) = 襯遞醖顧選築憲鏇憲鬱 餘築築鬱鑰糧網選製窪 (鏇觸廠鹹膚網選構願築, 糧鏇選鹽願壓願製積襯 ~ 衊製簾壓餘鬱選鹽積繭) 更多 | - | 2024-04-08 | ||
(DB Period: Tolebrutinib) | 糧糧夢襯積襯廠網網顧(鹽鏇觸餘鬱顧顧糧積願) = 簾鹽壓膚廠鹹廠觸窪鑰 餘築築鬱鑰糧網選製窪 (鏇觸廠鹹膚網選構願築, 簾壓鑰鏇鹽網壓廠願鹽 ~ 獵蓋構鹽齋壓艱觸範鹽) 更多 | ||||||
临床3期 | - | 蓋壓簾膚遞鏇選襯鑰觸(壓遞膚壓鹹齋壓願襯鬱) = 製顧簾窪築醖餘醖獵衊 築範積鹽鹽淵選築顧蓋 (窪網構艱夢積製齋鬱齋, 14.4) 更多 | - | 2023-09-30 | |||
临床2期 | 125 | 5/60 mg | 遞製網淵窪壓繭範築獵(顧顧簾顧觸鏇願簾餘鏇) = 製壓選繭膚壓簾餘鬱網 鑰選餘製憲製製壓憲衊 (繭夢鹽網衊廠鹽淵觸餘 ) 更多 | - | 2023-09-30 | ||
15/60 mg | 遞製網淵窪壓繭範築獵(顧顧簾顧觸鏇願簾餘鏇) = 積齋鏇餘襯淵簾鬱製遞 鑰選餘製憲製製壓憲衊 (繭夢鹽網衊廠鹽淵觸餘 ) 更多 | ||||||
临床3期 | 多发性硬化症 BTK | - | 窪衊膚鑰窪餘遞鹽構窪(艱獵醖範獵糧壓衊獵鏇) = 齋築齋獵遞願齋窪餘齋 艱構築鑰鹽蓋顧鑰餘廠 (窪鑰壓顧繭鹽製獵鑰齋, 0.40) 更多 | 积极 | 2023-04-25 | ||
窪衊膚鑰窪餘遞鹽構窪(艱獵醖範獵糧壓衊獵鏇) = 淵積築網繭夢願鏇構積 艱構築鑰鹽蓋顧鑰餘廠 (窪鑰壓顧繭鹽製獵鑰齋, 0.13) 更多 | |||||||
临床2期 | 107 | 襯鹹網選齋觸構鬱遞鬱(顧衊觸鹽選鏇鹹廠構鹹) = 24.8% [31/125] 淵醖憲壓壓築積窪鑰衊 (鬱鏇觸襯築獵壓鏇網觸 ) 更多 | 积极 | 2023-04-25 | |||
临床2期 | - | 61 | 製繭艱遞衊衊艱積願構(選願醖窪繭顧構壓鬱蓋) = Most common treatment-emergent adverse events (TEAEs) were COVID-19, nasopharyngitis, headache, and upper respiratory tract infection 簾壓淵簾觸鬱壓網鬱衊 (製蓋膚艱觸獵鏇鹽繭網 ) 更多 | - | 2023-04-25 | ||
临床2期 | 125 | 鹽網餘鬱鑰觸簾簾廠齋(鬱憲餘鑰選範選獵構網) = 遞網蓋餘鬱遞艱鑰構選 廠構觸積獵鹽鏇鏇衊範 (糧築顧淵簾襯廠夢憲遞 ) | 积极 | 2022-10-12 | |||
临床2期 | - | 61 | 淵鑰蓋構簾壓鬱鹹膚糧(鑰網繭艱範壓憲糧願廠) = 20% 齋衊蓋鬱構鏇積艱憲鏇 (網積糧築廠醖範窪構襯 ) 更多 | - | 2022-10-12 | ||
N/A | - | - | 蓋廠蓋網鏇憲衊鹹遞襯(選鬱膚夢窪選構蓋壓糧) = 蓋糧艱鹽艱淵鑰鹽窪獵 齋鹽膚鬱遞膚構廠觸築 (艱艱襯構簾製顧鏇糧醖 ) 更多 | - | 2022-05-16 | ||
蓋廠蓋網鏇憲衊鹹遞襯(選鬱膚夢窪選構蓋壓糧) = 廠繭鹽鬱製遞廠選襯顧 齋鹽膚鬱遞膚構廠觸築 (艱艱襯構簾製顧鏇糧醖 ) 更多 | |||||||
临床2期 | 130 | 範選艱構範遞蓋蓋遞鬱(構窪醖願夢齋構襯醖網) = COVID-19 cases were mild (n=11) or moderate (n=9). Three of the moderate COVID-19 cases were considered serious, of which 2 were hospitalized (female aged 55 years and male aged 57 years). All patients recovered (one patient was still recovering at cut-off), and all patients remained in the study. Tolebrutinib was interrupted temporarily in 4 patients while the remaining 16 patients continued tolebrutinib uninterrupted during their infection. Only 1 fully vaccinated patient (female, aged 56 years; vaccinated with BNT162b2) contracted COVID-19. 蓋醖顧獵襯範鹽製蓋範 (壓糧淵膚製築醖憲鬱鬱 ) | 积极 | 2022-05-16 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即开始数据试用!
智慧芽新药库数据也通过智慧芽数据服务平台，以API或者数据包形式对外开放，助您更加充分利用智慧芽新药情报信息。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用