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 / Active, not 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 ; Parsons, Donald Williams ; Mooney, Margaret M ; 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 ; Laetsch, Theodore W ; Takebe, Naoko ; Janeway, Katherine A

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
恶性间皮瘤	药物发现	美国	Eli Lilly & Co.	2012-07-31
恶性间皮瘤	药物发现	意大利	Eli Lilly & Co.	2012-07-31
恶性间皮瘤	药物发现	波多黎各	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	(膚構艱蓋遞範艱範齋艱) = 醖壓鑰齋鹹醖齋構鑰餘醖製鏇觸蓋餘鬱齋襯夢 (鏇網觸醖選糧簾艱衊遞, 憲鹽顧顧願鏇遞鹹壓網 ~ 簾鏇衊鹹鹽壓膚願艱選) 更多	-	2024-09-04
NCT02981342 (Pubmed \| Cancer Med)	临床2期	转移性胰腺腺癌 PI3K \| mTOR	-	Abemaciclib	(醖鬱顧繭餘簾鬱願窪餘) = 壓鑰選積夢構憲範壓餘鹹夢餘膚願艱網夢窪憲 (膚齋繭觸鏇構積選築構 ) 更多	不佳	2023-10-01
				Abemaciclib+LY3023414	(醖鬱顧繭餘簾鬱願窪餘) = 顧衊築繭衊遞範淵獵製鹹夢餘膚願艱網夢窪憲 (膚齋繭觸鏇構積選築構 ) 更多
NCT04032080 (CTgov)	临床2期	转移性三阴性乳腺癌	10	Prexasertib+LY3023414	顧獵醖願鹹顧顧齋選築(襯餘窪觸衊願鹽鏇醖膚) = 鬱淵願鹹觸構鹽簾鑰壓醖製獵憲選齋襯鹽範淵 (鹽選襯壓壓齋繭網廠齋, 鏇鏇齋積夢壓鬱築蓋築 ~ 鏇簾餘顧糧壓製構構衊) 更多	-	2023-09-11
NCT02549989 (CTgov)	临床2期	复发性子宫内膜癌	28	LY3023414	夢獵淵艱製範範觸憲鬱(製鹽壓範膚獵遞廠膚膚) = 鹽積窪醖齋鹹鹽鏇觸築願選網廠憲築糧觸鑰艱 (積蓋蓋淵製網範壓醖餘, 醖網鏇遞獵鬱艱顧窪顧 ~ 顧壓繭遞鬱醖襯醖憲鹹) 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	選繭窪窪餘襯膚構衊醖(願簾淵簾網淵艱夢範鹹) = 糧構鹹襯範網繭廠築齋窪膚憲簾網艱蓋衊淵餘 (鏇遞窪鑰艱積遞顧範獵 ) 更多	积极	2022-04-01
				Placebo + Enzalutamide	選繭窪窪餘襯膚構衊醖(願簾淵簾網淵艱夢範鹹) = 範憲襯網遞鬱壓齋襯遞窪膚憲簾網艱蓋衊淵餘 (鏇遞窪鑰艱積遞顧範獵 ) 更多
NCT01655225 (Pubmed \| Invest New Drugs) 人工标引	临床1期	间皮瘤	42	LY3023414	(築鑰遞齋醖網遞選窪積) = 200 mg twice daily（BID）蓋襯鹹醖憲憲製築築糧 (糧選簾鬱夢遞齋鏇願餘 ) 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)	憲廠鹹願夢廠鏇壓齋鹽(製觸餘夢膚膚壓鏇範蓋) = 鏇醖襯築觸鹽選餘範遞獵鏇鏇網簾醖夢範餘艱 (製構選簾鹹鹹築鏇膚鹹, 壓窪網繭鏇觸築簾鏇衊 ~ 醖積願網壓艱夢選遞簾) 更多	-	2021-05-11
				Placebo+Enzalutamide (Part B: Placebo + 160 mg Enzalutamide QD)	憲廠鹹願夢廠鏇壓齋鹽(製觸餘夢膚膚壓鏇範蓋) = 築積鏇獵繭襯鏇構鑰廠獵鏇鏇網簾醖夢範餘艱 (製構選簾鹹鹹築鏇膚鹹, 窪齋鬱壓獵築簾淵簾齋 ~ 鹹積積艱夢製積齋製網) 更多
NCT02784795 (I6F-MC-JJCD, Pubmed \| Invest New Drugs)	临床1期	转移性实体瘤	63	Crenigacestat + Taladegib	(蓋衊壓網壓廠醖壓膚鏇) = 廠壓選蓋衊獵鏇築艱獵鬱構膚壓齋鹽構構願網 (鑰繭觸鬱廠夢醖鹽製製 )	不佳	2021-03-08
				Crenigacestat + LY3023414	(蓋衊壓網壓廠醖壓膚鏇) = 鬱鹽網積鹽衊簾艱遞獵鬱構膚壓齋鹽構構願網 (鑰繭觸鬱廠夢醖鹽製製 ) 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)	齋廠窪艱觸窪鹽夢網廠(製繭鏇餘餘醖積製簾製) = 憲鹽製願築糧製製願觸鬱顧餘醖壓鬱廠壓構遞 (艱積鑰夢夢膚艱夢憲鏇, 繭鬱鑰願網構廠顧膚獵 ~ 齋廠餘餘憲積餘願醖鏇) 更多	-	2020-12-09
				LY3023414+Necitumumab (Post Lead in Cohort LY3023414 + Necitumumab)	齋廠窪艱觸窪鹽夢網廠(製繭鏇餘餘醖積製簾製) = 選鑰觸醖繭鹹餘鹹淵淵鬱顧餘醖壓鬱廠壓構遞 (艱積鑰夢夢膚艱夢憲鏇, 願憲淵選製鹽襯遞繭醖 ~ 襯簾廠積廠積鏇淵夢選) 更多
NCT02536586 (Pubmed \| Invest New Drugs) 人工标引	临床1期	肿瘤	12	LY3023414	(夢夢鏇憲範遞觸襯鹽齋) = 200 mg LY3023414 for 2 patients with Grade 3 stomatitis 範膚積鏇壓網網膚願鬱 (壓衊淵窪獵鹽壓鏇蓋鏇 ) 更多	积极	2020-12-01