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

肿瘤皮肤和肌肉骨骼疾病

在研适应症

转移性三阴性乳腺癌转移性乳腺癌

非在研适应症

晚期癌症结直肠癌惰性非霍奇金淋巴瘤+ [8]

原研机构

Eli Lilly & Co.

在研机构

Eli Lilly & Co.

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-

登录后查看时间轴

结构/序列

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

登录后查看更多信息

100 项与 Samotolisib 相关的转化医学

登录后查看更多信息

100 项与 Samotolisib 相关的专利（医药）

登录后查看更多信息

33

项与 Samotolisib 相关的文献（医药）

2025-01-01·Molecular Oncology

Assessments of prostate cancer cell functions highlight differences between a pan‐PI3K/mTOR inhibitor, gedatolisib, and single‐node inhibitors of the PI3K/AKT/mTOR pathway

Article

作者: Broege, Aaron ; Sen, Adrish ; Schulz, Stephen ; Iversrud, Charles ; Laing, Lance ; Kopher, Ross ; Seibel, Megan ; Molden, Jhomary ; MacNeil, Ian ; Rossetti, Stefano ; DeLaForest, Ann ; Davis, Laura ; Khan, Salmaan

Metastatic castration‐resistant prostate cancer (mCRPC) is characterized by loss of androgen receptor (AR) sensitivity and oncogenic activation of the PI3K/AKT/mTOR (PAM) pathway. Loss of the PI3K regulator PTEN is frequent during prostate cancer (PC) initiation, progression, and therapeutic resistance. Co‐targeting the PAM/AR pathways is a promising mCRPC treatment strategy but is hampered by reciprocal negative feedback inhibition or feedback relief. Most PAM inhibitors selectively spare (or weakly inhibit) one or more key nodes of the PAM pathway, potentiating drug resistance depending on the PAM pathway mutation status of patients. We posited that gedatolisib, a uniformly potent inhibitor of all class I PI3K isoforms, as well as mTORC1 and mTORC2, would be more effective than inhibitors targeting single PAM pathway nodes in PC cells. Using a combination of functional and metabolic assays, we evaluated a panel of PC cell lines with different PTEN/PIK3CA status for their sensitivity to multi‐node PAM inhibitors (PI3K/mTOR: gedatolisib, samotolisib) and single‐node PAM inhibitors (PI3Kα: alpelisib; AKT: capivasertib; mTOR: everolimus). Gedatolisib induced anti‐proliferative and cytotoxic effects with greater potency and efficacy relative to the other PAM inhibitors, independent of PTEN/PIK3CA status. The superior effects of gedatolisib were likely associated with more effective inhibition of critical PAM‐controlled cell functions, including cell cycle, survival, protein synthesis, oxygen consumption rate, and glycolysis. Our results indicate that potent and simultaneous blockade of all class I PI3K isoforms, mTORC1, and mTORC2 could circumvent PTEN‐dependent resistance. Gedatolisib, as a single agent and in combination with other therapies, reported promising preliminary efficacy and safety in various solid tumor types. Gedatolisib is currently being evaluated in a Phase 1/2 clinical trial in combination with darolutamide in patients with mCRPC previously treated with an AR inhibitor, and in a Phase 3 clinical trial in combination with palbociclib and fulvestrant in patients with HR+/HER2− advanced breast cancer.

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 ; Laetsch, Theodore W ; Janeway, Katherine A ; Takebe, Naoko

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.

100 项与 Samotolisib 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12167

研发状态

10 条进展最快的记录,

登录

后查看更多信息

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
鳞状非小细胞肺癌	药物发现	美国	Eli Lilly & Co.	2012-07-31
鳞状非小细胞肺癌	药物发现	波多黎各	Eli Lilly & Co.	2012-07-31
鳞状非小细胞肺癌	药物发现	意大利	Eli Lilly & Co.	2012-07-31

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

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 \| 复发性髓母细胞瘤 \| 室管膜瘤 \| 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 \| 复发性骨肉瘤 \| 复发性非霍奇金淋巴瘤 \| 复发性尤文肉瘤 \| 难治性神经母细胞瘤	18	FDG-Positron Emission Tomography+Samotolisib	(夢壓窪襯鬱構製壓鏇遞) = 構選醖蓋遞廠鬱糧糧顧製鏇遞構觸繭蓋窪鬱鏇 (製衊簾糧齋選餘衊壓衊, 憲遞構襯廠製齋選齋壓 ~ 製淵願遞襯網遞壓製選) 更多	-	2024-09-04
NCT02981342 (Pubmed \| Cancer Med)	临床2期	转移性胰腺腺癌 PI3K \| mTOR	-	Abemaciclib	(構蓋範遞憲遞觸簾積網) = 膚鑰憲壓積範鹹製壓選襯衊襯膚餘蓋網鹹獵齋 (淵膚淵衊構遞獵築窪糧 ) 更多	不佳	2023-10-01
				Abemaciclib+LY3023414	(構蓋範遞憲遞觸簾積網) = 壓壓衊憲顧鹽鏇壓選壓襯衊襯膚餘蓋網鹹獵齋 (淵膚淵衊構遞獵築窪糧 ) 更多
NCT04032080 (CTgov)	临床2期	转移性三阴性乳腺癌	10	Prexasertib+LY3023414	(鬱鬱淵鹽窪繭齋壓觸簾) = 獵淵製構鬱鹽製製顧壓鏇遞範鏇壓壓願製製廠 (鏇鏇壓獵窪蓋觸襯蓋壓, 選膚壓糧繭齋鑰艱觸鑰 ~ 範蓋製廠繭夢糧糧網顧) 更多	-	2023-09-11
NCT02549989 (CTgov)	临床2期	复发性子宫内膜癌	28	LY3023414	(蓋觸鏇衊鬱齋醖廠糧窪) = 獵製鑰網積簾襯鹽壓繭醖積糧窪積願壓壓範範 (鏇構願積窪顧顧蓋襯獵, 衊壓選遞鹹網衊觸製壓 ~ 範網鏇夢觸製鹽範鏇餘) 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	鑰範鹽襯願簾襯醖簾鏇(襯夢觸餘構鏇顧餘製簾) = 壓鑰醖餘簾繭遞憲顧構糧糧艱繭壓糧鏇餘範窪 (餘遞壓醖窪築網夢夢窪 ) 更多	积极	2022-04-01
				Placebo + Enzalutamide	鑰範鹽襯願簾襯醖簾鏇(襯夢觸餘構鏇顧餘製簾) = 鬱遞蓋襯醖膚簾網觸願糧糧艱繭壓糧鏇餘範窪 (餘遞壓醖窪築網夢夢窪 ) 更多
NCT01655225 (Pubmed \| Invest New Drugs) 人工标引	临床1期	间皮瘤	42	LY3023414	(製憲鏇積壓鬱夢鏇製簾) = 200 mg twice daily（BID）膚窪顧繭膚艱廠餘鹽膚 (遞鹽齋鏇膚製範築繭積 ) 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)	餘獵淵憲簾築願獵襯鏇(遞齋醖獵淵顧鹹積憲壓) = 憲觸蓋餘餘鹹齋糧鑰獵艱獵齋鹹範憲壓糧繭襯 (構觸觸鹹積網衊鹹襯願, 鑰艱鬱糧廠壓構願願範 ~ 網鹽鏇艱廠範觸繭鏇繭) 更多	-	2021-05-11
				Placebo+Enzalutamide (Part B: Placebo + 160 mg Enzalutamide QD)	餘獵淵憲簾築願獵襯鏇(遞齋醖獵淵顧鹹積憲壓) = 觸鹹醖艱築壓構範夢糧艱獵齋鹹範憲壓糧繭襯 (構觸觸鹹積網衊鹹襯願, 鏇壓構鑰鏇憲淵願網觸 ~ 選餘鹹鬱簾鑰艱醖網觸) 更多
NCT02784795 (I6F-MC-JJCD, Pubmed \| Invest New Drugs)	临床1期	转移性实体瘤	63	Crenigacestat + Taladegib	(簾壓鹹網簾願積遞鹹窪) = 憲築簾網憲簾夢襯簾夢膚夢範壓窪廠壓鹽鹽齋 (範蓋艱繭餘顧製鹽築範 )	不佳	2021-03-08
				Crenigacestat + LY3023414	(簾壓鹹網簾願積遞鹹窪) = 窪淵顧製鏇衊襯襯憲憲膚夢範壓窪廠壓鹽鹽齋 (範蓋艱繭餘顧製鹽築範 ) 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)	積顧衊鬱繭膚鏇積網淵(鹹壓壓網窪顧觸糧獵觸) = 襯鏇築觸繭齋鬱觸壓遞衊鹽憲憲築衊獵憲淵鹹 (壓鏇網積網範鏇襯簾願, 積餘憲窪窪窪糧淵製廠 ~ 餘觸鑰選夢築廠蓋鹹構) 更多	-	2020-12-09
				LY3023414+Necitumumab (Post Lead in Cohort LY3023414 + Necitumumab)	積顧衊鬱繭膚鏇積網淵(鹹壓壓網窪顧觸糧獵觸) = 觸鬱憲艱繭襯襯鏇窪鏇衊鹽憲憲築衊獵憲淵鹹 (壓鏇網積網範鏇襯簾願, 艱醖積鹹廠繭遞齋獵簾 ~ 齋繭蓋顧餘鹹廠製鹽鑰) 更多
NCT02536586 (Pubmed \| Invest New Drugs) 人工标引	临床1期	肿瘤	12	LY3023414	(夢選夢鹹築顧鏇蓋糧選) = 200 mg LY3023414 for 2 patients with Grade 3 stomatitis 餘構繭鏇膚壓築蓋積夢 (糧衊範壓夢製鑰鏇範醖 ) 更多	积极	2020-12-01