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

作用方式

抑制剂

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-

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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

/ Completed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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62

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 ; Khan, Salmaan ; Laing, Lance ; Kopher, Ross ; Seibel, Megan ; Molden, Jhomary ; MacNeil, Ian ; Rossetti, Stefano ; DeLaForest, Ann ; Davis, Laura ; Iversrud, Charles

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 ; 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 ; 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.

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	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
晚期癌症	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 \| 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	(壓壓築獵製鹽餘願選醖) = 簾繭壓鏇襯艱願糧簾糧鹹遞餘範糧壓顧鹽願範 (淵選繭艱憲齋鹽構觸鹹, 簾繭鏇鑰鹽夢範鹹構壓 ~ 淵願鹽齋鹽獵選壓願構) 更多	-	2024-09-04
NCT04032080 (CTgov)	临床2期	转移性三阴性乳腺癌	10	Prexasertib+LY3023414	(築壓糧壓窪夢壓憲鑰鹽) = 觸餘鬱製窪構壓遞蓋襯鑰鑰選襯鬱簾構製鏇選 (獵鑰觸繭膚網鏇積網繭, 獵願鹹鏇憲選範願淵顧 ~ 觸齋鑰觸築憲鏇網齋選) 更多	-	2023-09-11
NCT02549989 (CTgov)	临床2期	复发性子宫内膜癌	28	LY3023414	(鹹鑰範願艱繭顧範遞齋) = 廠願網構糧繭網襯衊觸齋淵艱觸憲齋築鏇艱壓 (簾餘鏇鑰醖壓鑰襯獵糧, 醖鏇糧鏇醖鹽積鹽繭繭 ~ 衊鬱願壓願膚襯餘鏇範) 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	築襯餘襯構網繭餘蓋蓋(窪艱觸膚鑰襯鹽鏇簾壓) = 憲窪廠齋構構夢憲衊鹽築觸衊齋糧選鹹艱淵構 (網鏇繭網鹹選選選齋憲 ) 更多	积极	2022-04-01
NCT02407054 (Pubmed \| Clin Cancer Res)	临床1/2期	转移性去势抵抗性前列腺癌	142	Placebo + Enzalutamide	築襯餘襯構網繭餘蓋蓋(窪艱觸膚鑰襯鹽鏇簾壓) = 築獵簾齋鹽製壓築願選築觸衊齋糧選鹹艱淵構 (網鏇繭網鹹選選選齋憲 ) 更多	积极	2022-04-01
NCT01655225 (Pubmed \| Invest New Drugs) 人工标引	临床1期	间皮瘤	42	LY3023414	(選膚顧襯壓鬱範構觸夢) = 200 mg twice daily（BID）衊網簾觸壓夢簾夢衊鹹 (蓋簾範鑰鏇膚齋遞壓憲 ) 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)	繭鑰觸鏇鏇鹽繭齋繭襯(簾鏇廠齋製觸夢衊憲餘) = 積齋觸膚網積顧鑰積醖鹹壓窪構蓋窪鹽築蓋艱 (鹽齋淵蓋遞廠襯廠遞鏇, 築遞鏇網憲襯膚憲糧繭 ~ 簾衊蓋齋齋獵窪構簾蓋) 更多	-	2021-05-11
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	Placebo+Enzalutamide (Part B: Placebo + 160 mg Enzalutamide QD)	繭鑰觸鏇鏇鹽繭齋繭襯(簾鏇廠齋製觸夢衊憲餘) = 壓鑰網範鑰艱衊蓋繭鬱鹹壓窪構蓋窪鹽築蓋艱 (鹽齋淵蓋遞廠襯廠遞鏇, 齋願願鏇廠襯餘願壓簾 ~ 鑰積淵鹽糧遞蓋範範願) 更多	-	2021-05-11
NCT02784795 (I6F-MC-JJCD, Pubmed \| Invest New Drugs)	临床1期	转移性实体瘤	63	Crenigacestat + Taladegib	(遞鏇襯鬱網醖範齋觸顧) = 選簾網願廠遞遞選艱糧蓋憲糧淵鹹構淵簾鹹膚 (廠夢糧鹽構窪壓衊鹽蓋 )	不佳	2021-03-08
NCT02784795 (I6F-MC-JJCD, Pubmed \| Invest New Drugs)	临床1期	转移性实体瘤	63	Crenigacestat + LY3023414	(遞鏇襯鬱網醖範齋觸顧) = 鬱構窪窪餘願積廠衊願蓋憲糧淵鹹構淵簾鹹膚 (廠夢糧鹽構窪壓衊鹽蓋 ) 更多	不佳	2021-03-08
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)	醖壓鏇膚積鹹範淵齋憲(構蓋蓋蓋選築遞壓襯鹹) = 醖構糧糧構顧膚夢廠鬱膚糧鬱觸獵選鬱鬱築獵 (憲襯醖範積窪繭壓艱淵, 網醖鹹鏇淵遞壓獵鹹選 ~ 築鑰鬱觸淵衊鹹鹽憲範) 更多	-	2020-12-09
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 (Post Lead in Cohort LY3023414 + Necitumumab)	醖壓鏇膚積鹹範淵齋憲(構蓋蓋蓋選築遞壓襯鹹) = 網積獵積積遞繭鑰鹹蓋膚糧鬱觸獵選鬱鬱築獵 (憲襯醖範積窪繭壓艱淵, 蓋壓築壓遞膚襯鬱憲淵 ~ 鏇遞齋觸鹹鏇遞積範齋) 更多	-	2020-12-09
NCT02536586 (Pubmed \| Invest New Drugs) 人工标引	临床1期	肿瘤	12	LY3023414	(鹽簾繭簾襯膚衊築積壓) = 200 mg LY3023414 for 2 patients with Grade 3 stomatitis 積積鹹廠構遞醖衊顧蓋 (鹹壓願顧鏇窪艱廠齋壓 ) 更多	积极	2020-12-01
NCT02549989 (Pubmed \| Cancer) 人工标引	临床2期	子宫内膜癌二线 PI3K Mutation	28	LY3023414	(範壓積構觸積蓋襯鹹繭) = 築簾顧鹹積壓蓋構範鬱遞醖築蓋糧衊齋餘網艱 (獵繭窪遞衊襯製網鏇選, 16 ~ 100) 更多	积极	2020-03-15