A Randomized, Open-label, Multi-Center, Phase 2 Clinical Trial Evaluating Sapanisertib and Serabelisib (PIKTOR) With Paclitaxel, Serabelisib With Paclitaxel, and Paclitaxel Alone in Patients With Advanced or Recurrent Endometrial Cancer

This is a Phase 2, multicenter, open-label, randomized study to evaluate the efficacy and safety of sapanisertib and serabelisib (PIKTOR) with paclitaxel and the efficacy and safety of serabelisib with paclitaxel versus paclitaxel alone in participants with advanced or recurrent endometrial cancer.

开始日期2024-09-30

申办/合作机构

Faeth Therapeutics, Inc.初创企业

[+1]

NCT05300048 / Active, not recruiting临床1期

A Phase 1b Study of Serabelisib in Combination With an Insulin Suppressing Diet (Study ISD) and With or Without Nab-paclitaxel in Adult Subjects With Advanced Solid Tumors With PIK3CA Mutations With or Without PTEN Loss

This study will evaluate the feasibility of optimizing the safety and tolerability of serabelisib (an investigational PI3K inhibitor) when combined with an ISD and with or without nab-paclitaxel with a goal of reducing side effects and enhancing anticancer activity.

开始日期2022-04-01

申办/合作机构

Faeth Therapeutics, Inc.初创企业

NCT04073680 / Unknown status临床1/2期

A Phase 1b/2 Study of Serabelisib in Combination With Canagliflozin in Patients With Advanced Solid Tumors With PIK3CA or KRAS Mutations

This study aims to test the hypothesis that combining serabelisib, a PI3K alpha isoform inhibitor, with an SGLT2 inhibitor, canagliflozin will improve efficacy in the treatment of patients with advanced solid tumors.

开始日期2020-09-01

申办/合作机构

Petra Pharma Corp.初创企业

100 项与色雷利塞相关的临床结果

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100 项与色雷利塞相关的转化医学

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100 项与色雷利塞相关的专利（医药）

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项与色雷利塞相关的文献（医药）

Advances in clinical and experimental medicine : official organ Wroclaw Medical University

Serabelisib regulates GSDMD-mediated pyroptosis, apoptosis and migration of hepatoma cells via the PI3K/Akt/E-cadherin signaling pathway

Article

作者: Li, Ming ; Huang, Zhao ; Zhou, Yuxiang

BACKGROUND:

Liver cancer is a malignant tumor commonly seen in infants and young children. Serabelisib is a novel and effective phosphoinositide-3-kinase (PI3Kα) inhibitor, currently in trials for solid malignancy treatment, such as bladder cancer. However, it is unclear whether serabelisib affects liver cancer.

OBJECTIVES:

To explore the effects of serabelisib on the proliferation, apoptosis, invasion, and metastasis of HepG2 and HuH-6 cells, and elucidate the relevant molecular mechanisms.

MATERIAL AND METHODS:

The HepG2 cells were treated with 2 μM, 4 μM or 8 μM serabelisib, while the 0-μM group was used as a control. A plate clone formation assay was utilized to measure colony formation ability in each group, a 5-ethynyl-2'-deoxyuridine (EdU) assay examined cell proliferation, a Cell Counting Kit-8 (CCK-8) assay assessed cell viability, flow cytometry measured the cell cycle and apoptosis, JC-1 staining determined mitochondrial membrane potential, and transmission electron microscopy evaluated cell morphology. In addition, gene and protein expression levels of apoptosis markers, epithelial-mesenchymal transition (EMT), Gasdermin D (GSDMD), and the PI3K/protein kinase B (AKT) signaling pathway were measured.

RESULTS:

After serabelisib intervention, HepG2 and HuH-6 cells formed fewer colonies, proliferated more slowly, and had reduced viability. The number of HepG2 and HuH-6 cells in the G2 and S phases decreased, apoptosis and the number of apoptotic bodies increased, and mitochondrial membrane potential decreased. Serabelisib treatment also reduced the migration and invasion capacity of the cells. Furthermore, genes and proteins of the PI3K/AKT signaling pathway were downregulated, while those that promote apoptosis and pyroptosis or inhibit EMT were upregulated.

CONCLUSIONS:

Serabelisib inhibited the PI3K/AKT signaling pathway, thereby inhibiting EMT and promoting apoptosis and pyroptosis in HepG2 and HuH-6 cells.

2023-11-01·Gynecologic oncology

A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer

Article

作者: Faller, Douglas V ; Han, Sileny N ; Makker, Vicky ; Jewell, Andrea ; Wenham, Robert M ; Alía, Eva María Guerra ; Sedarati, Farhad ; Vincent, Sylvie ; Raspagliesi, Francesco ; Neuwirth, Rachel ; Krell, Jonathan ; Baurain, Jean-François ; Su, Zhenqiang ; Braicu, Elena Ioana ; Oza, Amit ; Oaknin, Ana ; Scambia, Giovanni ; Colombo, Nicoletta

OBJECTIVE:

This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer.

METHODS:

Patients with histologic diagnosis of endometrial cancer (1-2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m² (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m² + oral sapanisertib 4 mg on days 2-4, 9-11, 16-18, and 23-25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1-3, 8-10, 15-17, and 22-24.

RESULTS:

Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58-1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43-1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib.

CONCLUSIONS:

Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable.

TRIAL REGISTRATION:

ClinicalTrials.gov number, NCT02725268.

2023-11-01·European journal of medicinal chemistry

Design, synthesis and bioevaluation of PI3Kα-selective inhibitors as potential colorectal cancer drugs

Article

作者: Chen, Yuan-Si ; Lei, Li ; Ban, Yu-Juan ; Zheng, Xue-Mei ; Tang, Lei ; Zhang, Ji-Quan ; Wang, Yu-Jie ; Li, Hong-Liang ; Guo, Bing ; Wang, Jian-Ta ; Dong, Yong-Xi

The dysregulation of the phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin signaling pathway has been implicated in various human cancers, and isoform-selective inhibitors targeting PI3Kα have received significant interest in recent years. In this study, we have designed and synthesized three series of substituted benzoxazole derivatives based on the clinical candidate TAK-117 (8a). A detailed structure-activity relationship (SAR) study has identified the optimal compound 18a bearing a quinoxaline scaffold. Compared to the control 8a, 18a exhibited 4.4-fold more potent inhibitory activity against PI3Kα (IC₅₀: 2.5 vs 11 nM) and better isoform-selective profiles over other PI3Ks. In addition, 18a showed a 1.5-fold more potent antiproliferative effect against HCT-116 cell lines (IC₅₀: 3.79 vs 5.80 μM) and a better selectivity over the normal tissue cells. The potential antitumor mechanism and in vitro metabolic stability of 18a were also investigated. Notably, pharmacokinetic assays indicated that 18a had a higher plasma exposure, a higher maximum concentration and shorter elimination time compared to 8a.

项与色雷利塞相关的新闻（医药）

2024-05-30

·BioSpace

Faeth Therapeutics to Participate in Upcoming Jefferies Investor Conference

Faeth’s CEO to showcase how AI has unlocked metabolism as a new cancer treatment paradigm AUSTIN, Texas--(BUSINESS WIRE)-- Faeth Therapeutics, (Faeth) a clinical-stage biotechnology company, announced today that Anand Parikh, Chief Executive Officer (CEO), will participate in one-on-one investor meetings at the upcoming Jefferies Global Healthcare Conference being held June 4-6 in New York. To schedule a meeting at the conference with Faeth’s CEO, please contact bridie@faeththerapeutics.com. For more information about the conference, please contact your institutional sales representative at Jefferies. Founded by renowned oncology researchers including Drs. Lew Cantley, Siddhartha Mukherjee, and Karen Vousden alongside CEO Anand Parikh, Faeth is focused on developing therapies targeting cancer metabolism. The role of metabolism in cancer proliferation is well established, yet remains a vastly under-exploited area, with very few cancer metabolism therapies in existence today. Faeth’s differentiated approach to targeting cancer metabolism leverages a systemic understanding of cancer metabolism, functional genomics, and computational biology to develop effective, less toxic therapies. Faeth has a robust clinical and preclinical pipeline driven by the company’s MetabOS discovery platform, which leverages AI, machine learning, and curated data sets to identify targets matched to specific tumor genotypes. Faeth's lead program, FTH-001/003, or "PIKTOR," includes serabelisib, a PI3Kɑ inhibitor, and sapanisertib, an mTORC 1/2 inhibitor, which together effectively shut down the PI3K pathway, the most commonly mutated pathway in cancer. PIKTOR, together with paclitaxel, has already shown outstanding results in a Phase 1b trial including endometrial, ovarian, and breast cancers. Faeth's second clinical program features FTH-002, a specially formulated amino acid sachet, which is administered in conjunction with an amino acid-restricted regimen and radio/chemotherapy. About Faeth Therapeutics Faeth Therapeutics is a clinical-stage biotechnology company at the forefront of oncology research with a robust clinical and preclinical pipeline powered by its AI-driven MetabOS discovery platform. Faeth’s lead program, PIKTOR, has shown outstanding clinical results in a Phase 1b trial and is advancing into a Phase 2 trial in endometrial cancer in 2024. For additional information, visit .

临床1期临床2期临床结果

2024-05-29

·CPHI制药在线

罗氏Inavolisib获FDA突破性疗法认定， PI3Kα抑制剂持续发力晚期乳腺癌

关注并星标CPHI制药在线5月21日，罗氏宣布美国FDA授予其在研口服疗法inavolisib突破性疗法认定，通过与palbociclib（哌柏西利）和fulvestrant（氟维司群）联合使用，用于治疗PIK3CA突变、激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）、在完成辅助内分泌治疗后或12个月内复发的局部晚期或转移性乳腺癌成年患者。Inavolisib是新一代PI3K抑制剂，兼具高选择性抑制PI3Κα与特异性降解PI3Κα突变蛋白功能的独特双重作用机制。就在上个月，inavolisib已被CDE纳入优先审评程序。 FDA的决定是基于III期INAVO120研究阳性结果。INAVO120研究（NCT04191499）是一项全球、多中心、双盲、随机对照的III期临床研究，旨在评估Inavolisib联合哌柏西利和氟维司群在PIK3CA突变的HR+/HER2-局部晚期或转移性乳腺癌患者中的疗效和安全性。结果显示，对比哌柏西利+氟维司群对照组，Inavolisib的加入令中位PFS翻倍，由7.3个月延长至15个月，具有统计学意义和临床意义的改善，并降低了57%的疾病进展或死亡风险（HR= 0.43，95%CI 0.32-0.59；p<0.0001）。在客观缓解率（ORR）和临床获益率（CBR）方面也观察到明显优势，Inavolisib+哌柏西利+氟维司群组ORR达58.4%，比对照组提高了33.4%（58.4% vs. 25.0%）；CBR达到了75.2%，比对照组提高了28.2%（75.2% vs. 47.0% ）。虽然OS方面虽然数据尚未成熟，但已观察到获益趋势。此外，inavolisib也在同步开展其他2项III期临床研究，分别是联合氟维司群 vs. alpelisib联合氟维司群用于既往接受过CDK4/6抑制剂和内分泌联合治疗的HR阳性/HER2阴性乳腺癌患者的INAVO121研究、联合帕妥珠单抗曲妥珠单抗皮下注射复方Phesgo）vs. Phesgo作为HER2阳性乳腺癌患者一线维持治疗的INAVO122研究。 PIK3CA基因与乳腺癌耐药 PAM通路中的PI3K是一种胞内磷脂酰肌醇激酶，又称磷脂酰肌醇3-激酶。它是一种二聚物体复合物，由催化亚基和调节亚基构成，根据不同的结构特点和底物分子可分为三类。其中研究最广泛的为I类PI3K，又分为IA类和IB类两个主要亚类。IA类PI3K包括PI3Kα、PI3Kβ、PI3Kδ，由其相对应的催化亚基p110（p110α、p110β、p110δ）和调节亚基p85组成。而PIK3CA基因可编码P110α蛋白，该蛋白在PIK3CA突变驱动的肿瘤生长和乳腺癌治疗耐药中发挥重要作用。CDK4/6抑制剂联合雌激素受体(ER)降解剂氟维司特可显著提高晚期激素受体阳性(HR+)乳腺癌患者的无进展生存期和总生存期，这是该疾病的标准治疗方法。然而，这种组合用药并不能治愈HR+乳腺癌患者，耐药性限制了临床受益的持续时间。在高达40%的HR+乳腺癌中，PIK3CA突变导致磷酸肌醇3-激酶α (PI3Kα)的激活，是耐药的关键驱动因素。因此，PI3Kα抑制剂联合CDK4/6抑制剂和/或氟维司特在预防和克服HR+、PIK3CA突变型乳腺癌的治疗耐药方面具有很高的市场价值。图片来源：参考来源2 Alpelisib将迎来Inavolisib正面PK 尽管PI3K抑制剂（包括选择性抑制剂与泛抑制剂）在血液瘤领域遭遇频繁撤市，但并未影响PI3Kα抑制剂在实体瘤领域的持续探索。诺华的Alpelisib（Piqray）是目前全球唯一获批上市的PI3Kα抑制，Piqray适应症为联合氟维司群治疗HR+/HER2-伴有PIK3CA突变的晚期或转移性乳腺癌。此后，alpelisib还在罕见病领域成功获批了第二项适应症，用于治疗PIK3CA相关过度生长疾病谱系（PROS）成人和2岁及以上儿童患者，alpelisib 2023年销售额达到5亿美元。值得注意的是，在NCCN指南中alpelisib联合氟维司群方案仅作为二线以及后线治疗推荐。而罗氏III期临床明确inavolisib组合作为一线治疗方案，瞄准的是患者群体更大的药物市场。换句话说，在当前获批的适应症下，inavolisib上市后的市场并不会受到alpelisib的影响，而因为患者在一线治疗已经使用了PI3Kα抑制剂，则有可能会影响临床医生二线治疗方案时再选择PI3Kα抑制剂，将会对alpelisib的市场造成冲击。此外，如上文所提及罗氏也开展了inavolisib与alpelisib的头对头研究，未来也将在二线及以上治疗市场中与alpelisib展开正面较量。由于alpelisib对wt和突变型PI3Kα均有抑制作用，选择性较差，临床中出现严重的高血糖副作用，65%患者出现高血糖，其中37%为3-4级AE。Inavolisib在III期临床中，有6.5%患者出现3-4级高血糖AE，这一点inavolisib有明显的优势。高达40%的HR+/HER2-晚期乳腺癌患者存在PIK3CA突变，在这一突变人群中inavolisib对比一线标准疗法，mPFS延长一倍以上（15.0个月vs7.3个月），拥有碾压性的临床优势，商业化前景可期。不仅是HER2阴性，罗氏同样在HER2阳性乳腺癌中联用帕妥珠/曲妥珠单抗一线维持开展了III期头对头研究，同样也是值得期待的大适应症。诺华和罗氏的接连成功，自然也吸引了很多药企开发选择性PI3Kα抑制剂，进入临床阶段的有Petra Pharm的Serabelisib、礼来的LOXO-783和Relay Therapeutics的RLY-2608等。国内方面，涉及到PI3Kα抑制剂研发的企业则有上海海和的CYH33、豪森的HS-10352和君实/润佳的JS105等。适应症包括晚期实体瘤、乳腺癌和复发/持续性卵巢、输卵管或原发性腹膜透明细胞癌等。进入临床阶段的高选择性PI3Kα抑制剂整理参考来源 1. André F, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019;380(20):1929-40 2. Overview of the relevance of PI3K pathway in HR-positive breast cancer. N Vasan, et al. Ann Oncol. 2019 Dec 1;30(Suppl_10):x3-x11. 3. He Y, et al. Targeting PI3K/Akt signal transduction for cancer therapy. Signals Transduction and Targeted Therapy. 2021; 6: 425 4. Juric et al. A phase I/Ib study of inavolisib (GDC-0077) in combination with fulvestrant in patients (pts) with PIK3CA-mutated hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer. Presented at San Antonio Breast Cancer Symposium, 2020 December 7-10; San Antonio, USA. Abstract #P5-17-05 5. Jhaveri K et al. Phase III study of inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: INAVO120 primary analysis. Presented at San Antonio Breast Cancer Symposium, 2023 December 5-9; San Antonio, USA. Abstract #GS03-13【企业推荐】来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

突破性疗法优先审批临床3期临床结果

2023-11-08

·BioSpace

Faeth Therapeutics to Participate in the Stifel 2023 Healthcare Conference

AUSTIN, Texas--(BUSINESS WIRE)-- Faeth Therapeutics, an oncology company with clinical programs combining therapeutics with metabolic optimization to achieve greater efficacy, today announced that the company will be participating in a company presentation and 1x1 investor meetings at the Stifel 2023 Healthcare Conference, taking place from November 14-15 in New York City. Anand Parikh, J.D., Chief Executive Officer & Co-Founder, Oliver Maddocks, PhD, Head of Research & Co-Founder, and Debbie Chirnomas, MD, Chief Medical Officer, will present a company overview on Wednesday, November 15, at 3:00 pm ET. About Faeth Therapeutics Faeth Therapeutics, headquartered in Austin, TX, is a clinical-stage biotechnology company focused on bringing breakthrough research in metabolic oncology into the clinic. The company leverages its machine-learning platform to develop precision therapies, augmented by a metabolic regimen involving the patient’s diet, to revolutionize the treatment paradigm. Faeth’s lead program combines FTH-001, serabelisib, with FTH-003, sapanisertib, and an insulin suppressing regimen to slow tumor growth by shutting down the PI3K/mTOR pathway. Faeth’s scientific founders include industry leaders Drs. Lew Cantley, Sid Mukherjee, Karen Vousden. For additional information, visit .

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床2期	-	Petra Pharma Corp.初创企业	2020-09-01
乳腺癌	临床2期	-	Petra Pharma Corp.初创企业	2020-09-01
结直肠癌	临床2期	-	Petra Pharma Corp.初创企业	2020-09-01
子宫内膜癌	临床2期	-	Petra Pharma Corp.初创企业	2020-09-01
头颈部肿瘤	临床2期	-	Petra Pharma Corp.初创企业	2020-09-01
肺癌	临床2期	-	Petra Pharma Corp.初创企业	2020-09-01
转移性三阴性乳腺癌	临床2期	美国	Takeda Pharmaceutical Co., Ltd.	2017-07-18
转移性透明细胞性肾细胞癌	临床2期	美国	Millennium Pharmaceuticals, Inc.	2016-06-30
转移性透明细胞性肾细胞癌	临床2期	加拿大	Millennium Pharmaceuticals, Inc.	2016-06-30
转移性透明细胞性肾细胞癌	临床2期	捷克	Millennium Pharmaceuticals, Inc.	2016-06-30

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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


NCT03193853 (CTgov)	临床2期	转移性三阴性乳腺癌	12	Nab Paclitaxel+Cisplatin+Tak-117+Tak-228	鹽衊願壓齋簾夢構築夢(遞觸窪淵築積蓋壓願憲) = 鹽蓋鏇繭餘鏇網齋網網夢餘選壓願鹹淵淵顧衊 (鹹鑰鏇襯齋壓廠築衊衊, 範鬱製構齋艱蓋襯鬱鏇 ~ 鏇鑰壓艱醖淵襯繭淵廠) 更多	-	2023-05-09
NCT03154294 (ASCO2021) 人工标引	临床1期	卵巢癌 \| 子宫内膜癌 \| 乳腺癌 PI3K Mutation \| AKT Mutation \| MTOR Mutation	19	paclitaxel+sapanisertib+serabelisib	築蓋繭鑰蓋構繭範繭獵(廠衊鏇築構繭顧夢網醖) = 鹹齋窪簾願糧積鹹憲襯鑰築範蓋壓糧餘鬱餘醖 (鹽選願觸範製廠齋壓齋 ) 更多	积极	2021-05-20
NCT02724020 (CTgov)	临床2期	转移性透明细胞性肾细胞癌	96	everolimus (Arm A: Single-agent Everolimus 10 mg QD)	選醖蓋窪觸積壓淵遞壓(淵鹽鬱構鑰膚憲築遞糧) = 壓鏇選遞蓋鹽簾範膚淵顧網構廠壓淵顧簾構憲 (膚廠鬱積鏇顧積憲憲範, 積襯憲遞願餘壓繭廠獵 ~ 衊糧蓋衊醖鑰繭窪築繭) 更多	-	2021-02-21
				MLN0128 (Arm B: Single-agent MLN0128 30 mg QW)	選醖蓋窪觸積壓淵遞壓(淵鹽鬱構鑰膚憲築遞糧) = 觸觸鏇淵獵構鹹鹹夢積顧網構廠壓淵顧簾構憲 (膚廠鬱積鏇顧積憲憲範, 窪夢網夢廠鏇鬱網憲積 ~ 顧築繭鑰選範鹽壓廠窪) 更多
NCT02725268 (CTgov)	临床2期	复发性子宫内膜癌	241	Paclitaxel (Paclitaxel 80 mg/m^2)	淵選窪願餘壓憲獵壓憲(簾齋憲窪鑰蓋齋顧窪壓) = 醖願衊鏇醖鑰糧鹹選醖醖鑰簾網製艱鬱餘獵顧 (艱膚衊構願願蓋選觸遞, 鹽製獵網夢簾壓繭獵壓 ~ 鹹餘簾鹽醖願鹹糧窪繭) 更多	-	2020-06-09
				Paclitaxel+Sapanisertib (Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg)	淵選窪願餘壓憲獵壓憲(簾齋憲窪鑰蓋齋顧窪壓) = 願範憲構觸蓋鏇範糧選醖鑰簾網製艱鬱餘獵顧 (艱膚衊構願願蓋選觸遞, 網齋範蓋蓋簾鹽選網襯 ~ 鹽襯積選鹽廠廠遞遞繭) 更多
NCT01449370 (ASCO2015)	临床1期	晚期恶性实体瘤	76	MLN1117 once daily (QD)	齋積艱獵製網選淵築積(鏇鏇積壓網廠範艱艱獵) = 衊鹽蓋鏇襯鹽襯餘願廠襯網積鏇鑰餘淵遞艱觸 (網餘淵窪築膚衊獵積網 ) 更多	-	2015-05-20
				MLN1117 3 days per week (MWF)	齋積艱獵製網選淵築積(鏇鏇積壓網廠範艱艱獵) = 鑰鬱鏇窪獵獵獵獵糧膚襯網積鏇鑰餘淵遞艱觸 (網餘淵窪築膚衊獵積網 ) 更多