更新于：2024-09-20
Senaparib
塞纳帕利
更新于：2024-09-20
概要
基本信息
药物类型 小分子化药 |
别名 IMP-04297、IMP-4297、JS109 |
作用机制 PARP1抑制剂(聚腺苷二磷酸核糖聚合酶1抑制剂)、PARP2抑制剂(聚腺苷二磷酸核糖聚合酶2抑制剂) |
非在研适应症 |
原研机构 |
在研机构 |
非在研机构  上海瑛派药业有限公司初创企业 |
最高研发阶段申请上市 |
首次获批日期- |
最高研发阶段(中国)申请上市 |
特殊审评孤儿药 (美国) |
结构
分子式C24H20F2N6O3 |
InChIKeyVBTUJTGLLREMNW-UHFFFAOYSA-N |
CAS号1401682-78-7 |
关联
27
项与 塞纳帕利 相关的临床试验An Open, Multicenter, Phase Ib/II Clinical Study of IMP4297 Capsule (JS109) Combined With Irinotecan in the Treatment of Advanced Malignant Solid Tumors
An Open-label, Randomized, Single-dose, Two-way Crossover Bioequivalence Study to Compare Two Strengths (10 mg and 20 mg) of IMP4297 Capsules in Healthy Chinese Subjects Under Fasting Condition
一项开放、随机、单剂量、二交叉、比较中国健康受试者在空腹状态下IMP4297胶囊两种规格（10 mg和20 mg）的生物等效性研究
100 项与 塞纳帕利 相关的临床结果
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100 项与 塞纳帕利 相关的转化医学
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100 项与 塞纳帕利 相关的专利（医药）
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5
项与 塞纳帕利 相关的文献（医药）2023-12-11The oncologist
Safety, Tolerability, and Pharmacokinetics of Senaparib, a Novel PARP1/2 Inhibitor, in Chinese Patients With Advanced Solid Tumors: A Phase I Trial
Article
作者: Edward Tian, Ye ; Ji, Dongmei ; Xiong Cai, Sui ; Xu, Cong ; Zhang, Pin ; Zhang, Shun ; Hsieh, Chih-Yi ; Cao, Junning ; Shen, Weina ; Guo, Hongqian ; Xu, Binghe
Abstract:
Background:
Senaparib, a novel poly(ADP-ribose) polymerase 1/2 inhibitor, demonstrated antitumor activity in preclinical studies. This phase I, first-in-human, dose-escalation/-expansion study explored the pharmacokinetics, safety and tolerability, and preliminary antitumor activity of senaparib in Chinese patients with advanced solid tumors.
Patients and Methods:
Adults with advanced solid tumors who had failed ³1 line of prior systemic treatment were enrolled. Senaparib (once daily [QD]) dose was escalated from 2 mg until the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) using a modified 3 + 3 design. Dose expansion included: dose groups with ≥1 objective response and one dose higher, as well as those at the MTD/RP2D. Primary objectives were to evaluate the safety and tolerability, and determine the MTD and/or RP2D of senaparib.
Results:
Fifty-seven patients were enrolled across 10 dose groups (2-120 mg QD, and 50 mg twice daily). No dose-limiting toxicities were observed. The most common senaparib-related adverse events were anemia (80.9%), white blood cell count decreased (43.9%), platelet count decreased (28.1%), and asthenia (26.3%). Senaparib exposure increased dose proportionately at 2-80 mg; absorption saturated at 80-120 mg. Senaparib accumulation was minimal after repeated QD administration (accumulation ratio=1.1-1.5). The objective response rate was 22.7% (n=10/44) overall (all partial responses) and 26.9% (n=7/26) for patients harboring BRCA1/BRCA2 mutations. Disease control rates were 63.6% and 73.1%, respectively.
Conclusions:
Senaparib was well tolerated and demonstrated promising antitumor activity in Chinese patients with advanced solid tumors. The RP2D for this clinical study in China was identified as 100 mg QD.
ClinicalTrials.gov Identifier:
NCT03508011
2023-06-01British journal of clinical pharmacology
Effect of a strong CYP3A4 inhibitor and inducer on the pharmacokinetics of senaparib (IMP4297) in healthy volunteers: A drug–drug interaction study
Article
作者: Cai, Sui Xiong ; Zhang, Yanxin ; Xu, Pingsheng ; Liu, Lan ; Zhang, Ming ; Xu, Sumei ; Hu, Xiaolei ; Shi, Huiyan ; Hsieh, Chih‐Yi ; Liu, Wanli ; Zhang, Hongxia ; Li, Xiaomin ; Liu, Ping
Aims:
A phase I open‐label study assessed the effect of multiple oral doses of a potent CYP3A4 inhibitor (itraconazole) and inducer (rifampicin) on the pharmacokinetic profile of a single oral dose of senaparib, a novel, highly potent poly‐(ADP‐ribose) polymerase 1/2 inhibitor and CYP3A4 substrate, in Chinese healthy male volunteers (HMV).
Methods:
Adult HMV were enrolled to the itraconazole or rifampicin group (n = 16 each). In Period 1, all participants received a single oral dose of senaparib 40 mg (itraconazole group) or 100 mg (rifampicin group). In Period 2, the same dose was coadministered with itraconazole (200 mg) and rifampicin (600 mg), respectively. The primary endpoints were senaparib exposure parameters.
Results:
Coadministration with itraconazole significantly increased exposure of senaparib and decreased that of its major metabolites M9 and M14. Maximum plasma senaparib concentration (Cmax) was increased by ~79% and area under the concentration–time curve (AUC) increased by ~2.8‐fold. Coadministration with rifampicin significantly reduced the Cmax and AUC of senaparib by ~59 and 83%, respectively. The Cmax for both M9 and M14 was slightly increased, although AUC was decreased. All treatment‐emergent adverse events were grade ≤2, regardless of the treatment administered.
Conclusion:
In Chinese HMV, the exposure of senaparib was significantly increased when coadministered with itraconazole and significantly decreased when coadministered with rifampicin. It is recommended to avoid concomitant use of senaparib and strong inhibitors or inducers of CYP3A4.
2023-04-01Cancer
A phase 1 dose‐escalation study of the poly(ADP‐ribose) polymerase inhibitor senaparib in Australian patients with advanced solid tumors
Article
作者: de Souza, Paul ; Voskoboynik, Mark ; Zhang, Ming ; Cooper, Adam ; Li, Baoyue ; Ma, Ning ; Gao, Bo ; Hoon, Siao ; Wang, Chen ; Wilkinson, Kate ; Tian, Ye Edward ; Xu, Cong ; Zhou, Ruiyu ; Wang, Xiaozhu ; Hsieh, Chih‐Yi ; Cai, Suixiong ; Bao, Jun ; Guo, Mingchuan
Abstract:
Background:
Senaparib is a novel, selective poly(ADP‐ribose) polymerase‐1/2 inhibitor with strong antitumor activity in preclinical studies. This first‐in‐human, phase 1, dose‐escalation study examined the safety and preliminary efficacy of senaparib in patients with advanced solid tumors.
Methods:
Patients with advanced solid tumors were enrolled from three centers in Australia, using a conventional 3 + 3 design. Dose‐escalation cohorts continued until the maximum tolerated dose or a recommended phase 2 dose was determined. Patients received one dose of oral senaparib and, if no dose‐limiting toxicity occurred within 7 days, they received senaparib once daily in 3‐week cycles. The primary end points were safety and tolerability.
Results:
Thirty‐nine patients were enrolled at 10 dose levels ranging from 2 to 150 mg. No dose‐limiting toxicities were observed in any cohort. Most treatment‐emergent adverse events were grade 1–2 (91%). Seven patients (17.9%) reported hematologic treatment‐emergent adverse events. Treatment‐related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib‐related bone marrow failure. Pharmacokinetic analysis indicated that senaparib the accumulation index was 1.06–1.67, and absorption saturation was 80–150 mg daily. In 22 patients with evaluable disease, the overall response rate was 13.6%, and the disease control rate was 81.8%. The overall response rate was 33.3% for the BRCA mutation‐positive subgroup and 6.3% for the nonmutated subgroup.
Conclusions:
Senaparib was well tolerated in Australian patients with advanced solid tumors, with encouraging signals of antitumor activity. The recommended phase 2 dose for senaparib was determined to be 100 mg daily.
ClinicalTrials.gov ID:
NCT03507543.
59
项与 塞纳帕利 相关的新闻（医药）2024-07-12
·华昊中天
免疫疗法临床研究
2024-07-11
·创鉴汇
快速通道临床3期临床2期抗体药物偶联物
2024-05-21
·生物探索
临床1期临床2期临床结果临床3期
100 项与 塞纳帕利 相关的药物交易
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研发状态
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 |
|---|---|---|---|---|
| 输卵管癌 | 申请上市 | 中国 | 2023-08-28 | |
| 输卵管癌 | 申请上市 | 中国 | 2023-08-28 | |
| 卵巢癌 | 申请上市 | 中国 | 2023-08-28 | |
| 卵巢癌 | 申请上市 | 中国 | 2023-08-28 | |
| 卵巢上皮癌 | 申请上市 | 中国 | 2023-08-28 | |
| 卵巢上皮癌 | 申请上市 | 中国 | 2023-08-28 | |
| 原发性腹膜癌 | 申请上市 | 中国 | 2023-08-28 | |
| 原发性腹膜癌 | 申请上市 | 中国 | 2023-08-28 | |
| 转移性去势抵抗性前列腺癌 | 临床2期 | 美国 | 2021-12-31 | |
| 转移性去势抵抗性前列腺癌 | 临床2期 | 中国 | 2021-12-31 |
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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3期 | 404 | 獵鏇夢構壓衊網餘鬱淵(淵鬱醖願膚鹹獵顧願膚) = Grade ≥3 treatment-emergent adverse events occurred in 66% and 20% of patients treated with Senaparib 100 mg and Placebo, respectively 艱夢鹹遞鏇鹹膚夢願願 (蓋鹹窪糧醖艱構膚廠獵 ) 更多 | 积极 | 2024-06-01 | |||
Placebo | |||||||
临床2期 | 卵巢癌 BRCA1 Mutation | BRCA2 Mutation | 93 | 淵鹽衊憲製餘齋繭糧鏇(獵鑰願蓋蓋網壓糧簾鹹) = 鏇網範繭壓衊繭糧範艱 齋構淵範鏇積築夢構鑰 (積壓繭蓋鹹鏇觸鹹願願, 86.2 ~ 97.5) 更多 | 积极 | 2023-10-22 | ||
临床3期 | 卵巢癌 维持 | 404 | 膚窪鏇觸襯鹹鹹鹹衊構(衊蓋醖醖範鑰蓋壓鏇艱) = 廠窪窪製獵糧構簾鏇艱 醖艱艱繭鬱願憲構窪窪 (襯範製鹽鹽鹹顧顧鏇壓 ) 更多 | 积极 | 2023-10-20 | ||
Placebo | 膚窪鏇觸襯鹹鹹鹹衊構(衊蓋醖醖範鑰蓋壓鏇艱) = 艱醖鏇窪鹹遞顧繭窪淵 醖艱艱繭鬱願憲構窪窪 (襯範製鹽鹽鹹顧顧鏇壓 ) 更多 | ||||||
临床3期 | 404 | 蓋鑰鹽鏇鏇簾蓋窪襯構(鏇膚鹹憲築鑰觸網鑰廠) = 淵簾選觸艱糧顧鑰艱醖 鬱淵願鹹齋鏇範餘鑰繭 (鹹鏇製壓願積築醖壓築 ) | 积极 | 2023-09-28 | |||
Placebo | 蓋鑰鹽鏇鏇簾蓋窪襯構(鏇膚鹹憲築鑰觸網鑰廠) = 構製積艱簾糧願鑰蓋淵 鬱淵願鹹齋鏇範餘鑰繭 (鹹鏇製壓願積築醖壓築 ) | ||||||
临床1/2期 | 42 | 遞蓋鏇鏇鏇鑰鑰網壓窪(憲製鏇構窪製齋膚夢範) = 齋憲獵簾襯鏇餘艱積醖 網餘膚齋夢範製獵窪壓 (構淵繭廠壓鑰襯膚膚顧, 5.4 ~ 28.5) 更多 | 积极 | 2023-09-12 | |||
(Platinum sensitive) | 遞蓋鏇鏇鏇鑰鑰網壓窪(憲製鏇構窪製齋膚夢範) = 蓋觸鏇壓醖觸窪觸網糧 網餘膚齋夢範製獵窪壓 (構淵繭廠壓鑰襯膚膚顧, 2.4 ~ 30.2) 更多 | ||||||
临床1期 | 57 | 糧衊淵願構築獵夢積艱(鹹鹽選艱衊觸構醖淵憲) = 簾構範繭遞構衊廠鑰衊 獵鹹膚鏇蓋廠築願鹹夢 (壓網遞憲簾壓鑰醖憲鏇 ) 更多 | - | 2023-06-20 | |||
临床1期 | 39 | 網獵鏇艱膚繭鹹衊範遞(範淵築醖觸淵觸壓齋築) = Most treatment-emergent adverse events were grade 1-2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. 窪蓋觸醖艱夢鏇遞鹹廠 (糧願窪鹽淵壓鏇齋廠憲 ) | - | 2023-01-31 | |||
临床1期 | 14 | 鹹獵顧壓鹹觸襯齋繭選(窪膚壓繭艱夢壓窪觸繭) = The MTD and RP2D were determined as: senaparib 80 mg plus temozolomide 20 mg. 憲願鏇願觸壓蓋築蓋窪 (齋廠網構糧醖襯簾廠獵 ) 更多 | 积极 | 2022-06-02 |
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