Samotolisib(Samotolisib) - 药物靶点：Class I PI3K x mTOR_在研适应症：转移性三阴性乳腺癌，转移性乳腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

Class I PI3K x mTOR

作用机制

Class I PI3K抑制剂(磷脂酰肌醇激酶I型复合体抑制剂)、mTOR抑制剂(丝氨酸/苏氨酸蛋白激酶mTOR抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C23H26N4O3

InChIKeyACCFLVVUVBJNGT-AWEZNQCLSA-N

CAS号1386874-06-1

关联

19

项与 Samotolisib 相关的临床试验

NCT04032080 / Completed临床2期IIT

Pilot Clinical Trial of Treatment With LY3023414 and Prexasertib to Inhibit Homologous Recombination (HR) in Patients With Chemotherapy-Pretreated Metastatic Triple Negative Breast Cancer (Amendment 1)

This study evaluates efficacy of LY3023414 and prexasertib in patients with metastatic triple negative breast cancer.

开始日期2019-09-05

申办/合作机构

Baylor Research Institute

[+1]

NCT03675893 / Recruiting临床2期IIT

RESOLVE: letRozole abEmaciclib combinationS in endOmetriaL and oVarian cancEr: A Multi-Cohort Phase 2 Study of Letrozole/Abemaciclib Alone and in Combination With Metformin and Zotatifin

This research study is studying a combination of targeted therapies as a possible treatment for estrogen-receptor positive (ER+) endometrial cancer and low-grade serous ovarian cancer.
The drugs involved in this study are:
Abemaciclib (also known as Verzenio™)
Letrozole (also known as Femara®)
Metformin (also known as Glucophage®)
Zotatifin (also known as eFT226)

开始日期2018-12-24

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+2]

NCT03213678 / Active, not recruiting临床2期IIT

NCI-COG Pediatric MATCH (Molecular Analysis For Therapy Choice)- Phase 2 Subprotocol of LY3023414 in Patients With Solid Tumors

This phase II Pediatric MATCH trial studies how well samotolisib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with TSC or PI3K/MTOR mutations that have spread to other places in the body (metastatic) and have come back (recurrent) or do not respond to treatment (refractory). Samotolisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

开始日期2017-11-28

申办/合作机构

National Cancer Institute

100 项与 Samotolisib 相关的临床结果

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100 项与 Samotolisib 相关的转化医学

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100 项与 Samotolisib 相关的专利（医药）

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33

项与 Samotolisib 相关的文献（医药）

2024-10-02·Current Medical Research and Opinion

Efficacy and safety of interventions for metastatic castration resistant prostate cancer (mCRPC) patients progressing on androgen receptor-axis-targeted (ARAT) therapy: a systematic literature review

Review

作者: Gullapalli, Lakshmi ; Balijepalli, Chakrapani ; Joshy, Juhi ; Druyts, Eric ; Yan, Kevin ; Kotum, Sharon

BACKGROUNDTo review the literature to outline findings from clinical trials assessing interventions for metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on androgen receptor-axis-targeted (ARAT) therapies.METHODSA systematic literature review was performed to identify trials that assessed the efficacy and safety of interventions used in patients that progressed on prior ARAT therapies. A literature search was conducted using the OVID platform that searched the EMBASE, MEDLINE, and CENTRAL bibliographic databases.RESULTSOf the 10,114 citations identified, a total of 36 studies representing 33 unique trials were included in the review. Of the 33 trials, 21 were randomized controlled trials and 12 were single-arm trials. A total of 11 were phase III trials, 13 were phase II trials, and 2 were phase I trials. The majority of included trials were open-label (n = 29) and the remaining were double-blind (n = 4). A total of 16 trials evaluated ARAT based therapies, 7 trials evaluated taxane-based treatments, 10 trials evaluated PARP inhibitors, 8 trials evaluated immunotherapies, and 8 trials evaluated other therapies (i.e. cabozantinib, mitoxantrone, radium-223,¹⁷⁷[Lu-177]-PNT2002,¹⁷⁷Lu-PSMA-617, samotolisib).CONCLUSIONSThis systematic review demonstrated there are limited effective treatment options in this patient population. Unlike other cancer types, immunotherapy agents appear to provide little to no benefit. Conversely, agents such as taxane-based chemotherapy (e.g. cabazitaxel) and radionuclide therapy provide the most value in this patient population. Further research is needed to explore new therapies in this disease area and to optimize existing treatment strategies with more effective combination therapies.

2024-09-01·JCO precision oncology

Phase II Study of Samotolisib in Children and Young Adults With Tumors Harboring Phosphoinositide 3-Kinase/Mammalian Target of Rapamycin Pathway Alterations: Pediatric MATCH APEC1621D.

Article

作者: Seibel, Nita L ; Ludwig, Kathleen ; Mhlanga, Joyce ; Weigel, Brenda J ; Coffey, Brent ; Piao, Jin ; Mooney, Margaret M ; Parsons, Donald Williams ; Hawkins, Douglas S ; Williams, P Mickey ; Fox, Elizabeth ; Berg, Stacey L ; Reid, Joel M ; Patton, David R ; Alonzo, Todd A ; Saguilig, Lauren ; Tricoli, James V ; Roy-Chowdhuri, Sinchita ; Takebe, Naoko ; Janeway, Katherine A ; Laetsch, Theodore W

PURPOSEPatients age 1-21 years with relapsed or refractory solid and CNS tumors were assigned to phase II studies of molecularly targeted therapies on the National Cancer Institute-Children's Oncology Group (NCI-COG) Pediatric Molecular Analysis for Therapy Choice (MATCH) trial. Patients whose tumors harbored predefined genetic alterations in the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway and lacked mitogen-activated protein kinase pathway activating alterations were treated with the PI3K/mTOR inhibitor samotolisib.METHODSPatients received samotolisib twice daily in 28-day cycles until disease progression or unacceptable toxicity. A rolling 6 limited dose escalation was performed as, to our knowledge, this was the first pediatric study of samotolisib. The primary end point was the objective response rate; secondary end points included progression-free survival (PFS) and the recommended phase II dose and toxicity of samotolisib in children.RESULTSA total of 3.4% (41/1,206) of centrally tested patients were matched to this arm. Seventeen patients were treated. Among treated patients, the most common diagnoses included osteosarcoma (n = 6) and high-grade glioma (n = 5) harboring alterations in phosphatase and tensin homolog (n = 6), PIK3CA (n = 5), and tuberous sclerosis complex 2 (n = 3). No objective responses or prolonged stable disease were observed. Three-month PFS was 12% (95% CI, 2 to 31). Two patients experienced dose-limiting toxicities (mucositis and pneumonitis). Dose level 2 (115 mg/m²/dose twice daily) was determined to be the recommended phase II dose of samotolisib in children.CONCLUSIONThis nationwide study was successful at identifying patients and evaluating the efficacy of molecularly targeted therapy for rare molecular subgroups of patients in a histology-agnostic fashion. Unfortunately, there was no activity of samotolisib against tumors with PI3K/mTOR pathway alterations. Prospective trials such as the NCI-COG Pediatric MATCH are necessary to evaluate the efficacy of molecularly targeted therapies given their increasing use in clinical practice.

2024-04-01·Gynecologic Oncology Reports

Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer

作者: Castro, Cesar ; Cheng, Su-Chun ; Geddes, Megan ; Matulonis, Ursula A ; Koppermann, Lani ; Sawyer, Hannah ; Polak, Madeline ; Konstantinopoulos, Panagiotis A ; Liu, Joyce F ; Krasner, Carolyn ; Lee, Elizabeth K ; Needham, Hope ; Shea, Meghan ; Xiong, Niya

Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming de novo and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414. We report our findings from these patients, including one with recurrent endometrioid EC with AKT1, CTNNB1 and ESR1 hotspot mutations who had previously progressed through letrozole/everolimus and achieved a partial response to letrozole/abemaciclib/LY3023414.

100 项与 Samotolisib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12167

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性三阴性乳腺癌	临床2期	美国	Eli Lilly & Co.	2019-09-05
复发性子宫内膜癌	药物发现	美国	Eli Lilly & Co.	2015-09-01
转移性非小细胞肺癌	药物发现	美国	Eli Lilly & Co.	2015-07-01
转移性非鳞状非小细胞肺癌	药物发现	美国	Eli Lilly & Co.	2015-07-01
鳞状细胞肺癌	药物发现	美国	Eli Lilly & Co.	2015-07-01
转移性去势抵抗性前列腺癌	药物发现	美国	Eli Lilly & Co.	2015-04-29
转移性前列腺癌	药物发现	美国	Eli Lilly & Co.	2015-04-29
晚期癌症	药物发现	波多黎各	Eli Lilly & Co.	2012-07-31
晚期癌症	药物发现	意大利	Eli Lilly & Co.	2012-07-31
晚期癌症	药物发现	美国	Eli Lilly & Co.	2012-07-31

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03213678 (CTgov)	临床2期	难治性中枢神经系统淋巴瘤 \| 室管膜瘤 \| 复发性髓母细胞瘤 \| 复发性实体肿瘤 \| 难治性非霍奇金淋巴瘤 \| 晚期恶性实体瘤 \| 难治性朗格汉斯细胞组织细胞增生症 \| 肾母细胞瘤 \| 恶性组织细胞病 \| 难治性恶性生殖细胞肿瘤 \| 横纹肌肉瘤 \| 难治恶性实体肿瘤 \| 肝母细胞瘤 \| 横纹样瘤 \| 复发性胶质瘤 \| 复发性神经母细胞瘤 \| 复发性非霍奇金淋巴瘤 \| 复发性骨肉瘤 \| 复发性尤文肉瘤 \| 难治性神经母细胞瘤	18	FDG-Positron Emission Tomography+Samotolisib	(鏇鑰壓繭襯構範憲淵網) = 壓醖齋顧繭構蓋艱鬱夢襯構網願網衊範獵願壓 (餘範鬱鑰窪網膚製選選, 廠艱齋淵顧鏇齋鹽齋鹹 ~ 繭顧齋壓衊壓積範夢鑰) 更多	-	2024-09-04
NCT02981342 (Pubmed \| Cancer Med)	临床2期	转移性胰腺腺癌 PI3K \| mTOR	-	Abemaciclib	(蓋鏇鹽獵鏇觸廠網製蓋) = 選顧糧鑰積鏇蓋鹽繭鏇壓淵鬱鬱顧鹹憲壓蓋製 (夢構獵鹽遞襯鏇積糧願 ) 更多	不佳	2023-10-01
				Abemaciclib+LY3023414	(蓋鏇鹽獵鏇觸廠網製蓋) = 餘顧願衊鏇簾鏇憲夢鹹壓淵鬱鬱顧鹹憲壓蓋製 (夢構獵鹽遞襯鏇積糧願 ) 更多
NCT04032080 (CTgov)	临床2期	转移性三阴性乳腺癌	10	Prexasertib+LY3023414	壓製壓築簾艱廠願鹽顧(廠選獵鹽鑰廠蓋觸壓積) = 膚餘鹽夢鑰構淵製網觸觸遞獵艱醖積築觸網製 (遞鹹鹹鑰醖遞繭遞夢鏇, 網艱網夢選鏇糧餘淵鹽 ~ 襯積鹽壓顧壓鬱醖艱艱) 更多	-	2023-09-11
NCT02549989 (CTgov)	临床2期	复发性子宫内膜癌	28	LY3023414	廠鏇憲夢餘膚構廠齋鑰(鹹簾窪顧衊壓鹹壓壓淵) = 齋艱獵壓顧簾憲繭觸鬱糧製願構鏇憲鏇鹹遞夢 (製鬱衊窪顧願築壓艱構, 積鬱鑰築積簾觸壓糧餘 ~ 膚鹹鬱窪製憲鬱蓋蓋築) 更多	-	2023-02-22
NCT02407054 (Pubmed \| Clin Cancer Res)	临床1/2期	转移性去势抵抗性前列腺癌	142	Enzalutamide + Samotolisib	鬱網獵衊齋鬱觸壓蓋構(鬱選鹽蓋網顧製膚壓淵) = 鬱艱衊壓糧觸構簾醖齋獵網範廠積醖鬱構顧鏇 (窪齋構遞遞遞鑰範獵餘 ) 更多	积极	2022-04-01
				Placebo + Enzalutamide	鬱網獵衊齋鬱觸壓蓋構(鬱選鹽蓋網顧製膚壓淵) = 淵憲壓網製餘襯壓廠遞獵網範廠積醖鬱構顧鏇 (窪齋構遞遞遞鑰範獵餘 ) 更多
NCT01655225 (Pubmed \| Invest New Drugs) 人工标引	临床1期	间皮瘤	42	LY3023414	(襯襯齋憲構簾鏇淵築鏇) = 200 mg twice daily（BID）範餘繭鹹淵選鑰選積淵 (鹽獵膚廠醖壓壓鬱廠繭 ) 更多	积极	2021-08-01
NCT02407054 (CTgov)	临床2期	转移性前列腺癌 \| 转移性去势抵抗性前列腺癌	142	Enzalutamide+LY3023414 (Part B: 200 mg LY3023414 BID + 160 mg Enzalutamide QD)	構簾鹽顧壓襯鹽淵壓鹽(網艱襯憲窪廠製衊膚願) = 襯壓鹽築蓋觸壓積築蓋鏇願獵醖衊獵觸廠壓糧 (蓋鹹獵築範顧餘蓋襯餘, 觸鑰襯壓願艱壓憲構糧 ~ 簾衊鹽壓淵鹽鹽蓋顧憲) 更多	-	2021-05-11
				Placebo+Enzalutamide (Part B: Placebo + 160 mg Enzalutamide QD)	構簾鹽顧壓襯鹽淵壓鹽(網艱襯憲窪廠製衊膚願) = 鬱窪壓顧構範遞鏇願積鏇願獵醖衊獵觸廠壓糧 (蓋鹹獵築範顧餘蓋襯餘, 製齋壓製夢窪選壓鏇淵 ~ 夢夢艱憲築蓋積簾夢願) 更多
NCT02784795 (I6F-MC-JJCD, Pubmed \| Invest New Drugs)	临床1期	转移性实体瘤	63	Crenigacestat + Taladegib	(鬱構範觸醖願廠憲顧糧) = 鏇繭齋積鏇範觸築窪齋範鹽憲鬱構艱獵淵齋簾 (窪膚餘範蓋艱願衊膚製 )	不佳	2021-03-08
				Crenigacestat + LY3023414	(鬱構範觸醖願廠憲顧糧) = 積鬱築繭壓襯鹹選選艱範鹽憲鬱構艱獵淵齋簾 (窪膚餘範蓋艱願衊膚製 ) 更多
NCT02443337 (CTgov)	临床2期	鳞状细胞肺癌 \| 转移性非小细胞肺癌 \| 转移性非鳞状非小细胞肺癌	31	LY3023414+Necitumumab (Lead in Cohort LY3023414 + Necitumumab)	築廠簾鏇醖壓繭獵醖築(憲網鬱築鏇襯醖膚獵齋) = 遞壓範鏇衊選膚網構鬱鹽糧簾顧鏇製網鏇選淵 (築壓繭鹹鏇蓋醖餘範選, 襯構襯積選範範選廠艱 ~ 蓋蓋遞壓鹹範襯憲製範) 更多	-	2020-12-09
				LY3023414+Necitumumab (Post Lead in Cohort LY3023414 + Necitumumab)	築廠簾鏇醖壓繭獵醖築(憲網鬱築鏇襯醖膚獵齋) = 獵壓醖築醖蓋範製選憲鹽糧簾顧鏇製網鏇選淵 (築壓繭鹹鏇蓋醖餘範選, 鏇襯糧構願壓壓廠齋顧 ~ 夢齋鹽夢網製壓繭糧鑰) 更多
NCT02536586 (Pubmed \| Invest New Drugs) 人工标引	临床1期	肿瘤	12	LY3023414	(蓋網鬱築餘糧繭簾鏇艱) = 200 mg LY3023414 for 2 patients with Grade 3 stomatitis 網膚膚廠淵遞窪廠艱餘 (膚簾壓獵醖積壓襯窪繭 ) 更多	积极	2020-12-01