Phase Ib Study on the Prevention of Graft-versus-host Disease (GVHD) in Children After Haploid Stem Cell Transplantation Using Cyclophosphamide (PTCy) Combined With Sirolimus and VIC-1911 Tablets

This study is a single arm, open label Phase Ib clinical trial, consisting of two parts: the first part is a safety introduction trial, and the second part is a dose escalation trial. In the first part, the tolerability, safety, PK characteristics, PD characteristics, and preliminary efficacy of VIC-1911 tablets in combination with PTCy and sirolimus will be explored. The first part will conduct safety introduction tests at the same dose as those already tested abroad to determine the dosage required for VIC-1911 tablets to meet safety and effective biological activity. The dose limiting toxicity (DLT) in Phase I study will be evaluated from the first administration of VIC-1911 tablets to 28 days after administration. On this basis, the second part of the experiment will be conducted to further explore the effectiveness and safety of VIC-1911 tablets combined with PTCy and sirolimus under RP2D for preventing GVHD in haplo HSCT patients after myeloablative pretreatment

开始日期2026-03-25

申办/合作机构

上海交通大学医学院

NCT06519721

/ RecruitingN/AIIT

Safety and Efficacy Study of Lenvatinib Combined With VIC-1911 for the Treatment of Advanced Hepatocellular Carcinoma

This study is a single-arm, open-label trial to clarify the safety and efficacy of the combined treatment of lenvatinib and VIC-1911 in patients with advanced liver cancer.

开始日期2024-08-01

申办/合作机构-

NCT05718882

/ Unknown statusN/AIIT

Safety and Efficacy of Lenvatinib Combined With VIC-1911 in the Treatment of Lenvatinib-unresponsive or Lenvatinib-resistant Hepatocellular Carcinoma

This is a prospective clinical study aiming to test the safety and efficacy of lenvatinib in combination with Aurora kinase A inhibitor VIC-1911 in participate with lenvatinib-unresponsive or lenvatinib-resistant hepatocellular carcinoma(HCC).

开始日期2023-07-01

申办/合作机构

上海交通大学医学院附属仁济医院

100 项与 TAS-119 相关的临床结果

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100 项与 TAS-119 相关的转化医学

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100 项与 TAS-119 相关的专利（医药）

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项与 TAS-119 相关的文献（医药）

2021-06-01·Investigational new drugs3区 · 医学

TAS-119, a novel selective Aurora A and TRK inhibitor, exhibits antitumor efficacy in preclinical models with deregulated activation of the Myc, β-Catenin, and TRK pathways

3区 · 医学

Article

作者: Ito, Kimihiro ; Uto, Yoshihiro ; Fujita, Naoya ; Sugimoto, Tetsuya ; Mitsuya, Morihiro ; Hirai, Hiroshi ; Miura, Akihiro ; Takahashi, Hidekazu ; Fukushima, Hiroto ; Mizuarai, Shinji ; Sootome, Hiroshi ; Masuko, Norio ; Suzuki, Takamasa ; Hashimoto, Akihiro

Aurora kinase A, a mitotic kinase that is overexpressed in various cancers, is a promising cancer drug target. Here, we performed preclinical characterization of TAS-119, a novel, orally active, and highly selective inhibitor of Aurora A. TAS-119 showed strong inhibitory effect against Aurora A, with an IC₅₀ value of 1.04 nmol/L. The compound was highly selective for Aurora A compared with 301 other protein kinases, including Aurora kinase B. TAS-119 induced the inhibition of Aurora A and accumulation of mitotic cells in vitro and in vivo. It suppressed the growth of various cancer cell lines harboring MYC family amplification and CTNNB1 mutation in vitro. In a xenograft model of human lung cancer cells harboring MYC amplification and CTNNB1 mutation, TAS-119 showed a strong antitumor activity at well-tolerated doses. TAS-119 induced N-Myc degradation and inhibited downstream transcriptional targets in MYCN-amplified neuroblastoma cell lines. It also demonstrated inhibitory effect against tropomyosin receptor kinase (TRK)A, TRKB, and TRKC, with an IC₅₀ value of 1.46, 1.53, and 1.47 nmol/L, respectively. TAS-119 inhibited TRK-fusion protein activity and exhibited robust growth inhibition of tumor cells via a deregulated TRK pathway in vitro and in vivo. Our study indicates the potential of TAS-119 as an anticancer drug, especially for patients harboring MYC amplification, CTNNB1 mutation, and NTRK fusion.

2021-01-19·British journal of cancer1区 · 医学

A first-in-human phase 1 and pharmacological study of TAS-119, a novel selective Aurora A kinase inhibitor in patients with advanced solid tumours

1区 · 医学

Article

作者: Robbrecht, Debbie G J ; Cook, Natalie ; de Bono, Johann S ; Hiroshi, Hirai ; Soni, Nital ; Fasolo, Angelica ; He, Xiaomin ; Eskens, Ferry A L M ; Lopez, Juanita ; Moreno, Victor ; Dowlati, Afshin ; Calvo, Emiliano

Abstract:

Background:

This is a first-in-human study with TAS-119, an Aurora A kinase (AurA) inhibitor.

Methods:

Patients with advanced, refractory, solid tumours were enrolled into 5 dose escalation cohorts (70–300 mg BID, 4 days on/3 days off, 3 out of 4 weeks or 4 out of 4 weeks). The expansion part consisted of patients with small-cell lung cancer, HER2-negative breast cancer,MYC-amplified/β-catenin-mutated (MT) tumours or other (basket cohort).

Results:

In the escalation part (n = 34 patients), dose-limiting toxicities were one grade 3 nausea, two grade 2 and one grade 3 ocular toxicity and a combination of fatigue, ocular toxicity and nausea in one patient (all grade 2) at dose levels of 150, 200, 250 and 300 mg, respectively. Most frequent treatment-related adverse events were fatigue (32%), diarrhoea (24%) and ocular toxicity (24%). Toxicity grade ≥3 in ≥10% of patients were diarrhoea (15%) and increased lipase (12%). The maximum tolerated dose was 250 mg BID. Due to one additional grade 1 ocular toxicity, the RP2D was set at 200 mg BID (4 days on/3 days off, 3 out of 4 weeks), which was further explored in the expansion part (n = 40 patients). Target inhibition in paired skin biopsies was shown.

Conclusions:

TAS-119 has a favourable and remarkably distinct safety profile from other AurA inhibitors.

Clinical trial registration:

NCT02448589.

2020-10-01·Molecular cancer therapeutics2区 · 医学

Aurora A Inhibitor TAS-119 Enhances Antitumor Efficacy of TaxanesIn VitroandIn Vivo: Preclinical Studies as Guidance for Clinical Development and Trial Design

2区 · 医学

Article

作者: Hirai, Hiroshi ; Sootome, Hiroshi ; Masuko, Norio ; Miura, Akihiro ; Suzuki, Takamasa ; Uto, Yoshihiro

Abstract:

TAS-119 is a novel orally active, selective inhibitor of Aurora kinase A identified as a clinical candidate for efficacy testing in combination with taxanes. In vitro, TAS-119 enhanced cell growth inhibition of paclitaxel in multiple human cancer cell lines derived from various tissues, including paclitaxel-resistant cell lines. Interestingly, TAS-119 did not enhance paclitaxel antitumor activity in normal lung diploid fibroblast cell lines WI-38 and MRC5. In vivo, TAS-119 enhanced the antitumor efficacy of paclitaxel and docetaxel in multiple models at doses inhibitory to Aurora A in tumors. Moreover, the drug combination was well tolerated, and TAS-119 did not exaggerate clinically documented side effects of taxanes, neutropenia and neurotoxicity, in rats. The same TAS-119 concentration enhanced the cell growth inhibitory activity of three clinically approved taxanes, paclitaxel, docetaxel, and cabazitaxel. The degree of enhancement calculated as fold of change of the IC50 value for each taxane was almost the same among the three taxanes. We conducted in vitro and in vivo experiments to develop an optimized combination therapy regimen for TAS-119 with paclitaxel/docetaxel. Using in vitro and in vivo models, we tested the drug administration order for TAS-119 combined with paclitaxel and the TAS-119 treatment duration. The best regimen in preclinical models was combining paclitaxel or docetaxel treatment with 4 days of TAS-119 dosing, which was initiated on the same day as the paclitaxel or docetaxel administration or one day later. This information provided guidance for the design of a clinical trial of TAS-119 and paclitaxel or docetaxel combination.

项与 TAS-119 相关的新闻（医药）

2024-06-01

·同写意

捷思英达将在2024 ASCO公布Aurora A抑制剂VIC-1911治疗肺癌的I期临床研究数据

同写意20岁庆！中国医药创新未来之路！“意”同创新，穿越周期，赢得未来。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！捷思英达将在2024年美国临床肿瘤学会年会（ASCO）公布极光激酶A （Aurora A）抑制剂VIC-1911治疗肺癌的I期临床研究数据，本次报告的标题为【Phase I trial of aurora kinase A（AURKA）Inhibitor VIC-1911 plus Osimertinib for TKI-resistant, EGFR-mutant non-small cell lung cancer（NSCLC）】，编号：8077。此项研究共入组了24例患者，剂量递增阶段入组了7例患者（150mg 4例，200mg 3例），未观察到DLT，后选择200mg作为RP2D。与VIC-1911相关的最常见不良反应为腹泻（52.3%）、白细胞减少（38.1%）、中性粒细胞减少（3.3%）和血小板减少（28.6%）。剂量扩展阶段入组了17例受试者。在总体可评价疗效的23例患者中，10例患者为未使用奥希替尼（T790m阴性8例，T790m阳性2例），13例患者为奥希替尼耐药。未使用奥希替尼患者的客观缓解率（ORR）为50% （5PRs, T790m阴性=4,T790m阳性=1），疾病控制率(DCR)为80%（3SDs）。对于奥希替尼耐药患者，ORR为0%，DCR为53.8%（7SDs)）。在疾病控制的患者中，66.7%（10/15）的患者在数据截止时仍在治疗中，中位随访时间为5.5个月，未达到中位缓解持续时间（DOR），6个月DOR率为50%。未使用奥希替尼和奥希替尼耐药患者的中位无进展生存期（PFS）分别为4.6个月和2.1个月，6个月无进展生存率分别为70.0%和38.5%。总体结果显示VIC-1911联合奥希替尼在既往接受过治疗的EGFR突变的非小细胞肺癌患者中具有良好的耐受性。联合用药也显示出持续的抗肿瘤活性，这表明阻断极光激酶A/AURKA在延缓奥希替尼耐药出现方面具有潜力。VIC-1911是新一代高选择性、临床安全的细胞周期调节激酶Aurora A抑制剂，目前在中美处于临床1b研究阶段，具备国际首创新药潜力。VIC-1911在干细胞移植后预防移植物抗宿主病（GVHD）和白血病复发的临床研究中初步展示很好的疗效（参见2023年12月美国血液肿瘤年会ASH会议报告）。关于捷思英达捷思英达是一家聚焦新一代肿瘤精准治疗新药研发的生物医药企业，公司核心业务致力于解决肿瘤新药研究的两个痛点：（a）精准靶向，改善药物的临床安全性和潜在治疗窗口；（b）肿瘤耐药解决方案。捷思英达和国内外最权威的临床医生和研究机构合作，开展国际前沿水平的转化医学研究和临床研究，目前已经在干细胞移植后预防GVHD和白血病复发，非小细胞肺癌，乳腺癌，黑色素瘤及其脑转移，头颈癌以及小细胞肺癌等领域取得重要进展。捷思英达目前有3个国家一类新药产品分别处于临床1期和临床II期研究阶段。近期直播推荐:

临床结果ASCO会议临床1期临床2期

2024-06-01

·医药观澜

捷思英达公布2款小分子抗肿瘤新药临床试验数据 | ASCO

▎药明康德内容团队报道5月31日消息，捷思英达宣布将在2024年美国临床肿瘤学会年会（ASCO）上公布两款在研新药临床试验数据，分别为：Aurora A抑制剂VIC-1911治疗肺癌的1期临床研究数据；以及ERK抑制剂JSI-1187治疗实体瘤的1期临床研究数据。VIC-1911：Aurora A抑制剂适应症：非小细胞肺癌VIC-1911是新一代高选择性、临床安全的细胞周期调节激酶Aurora A抑制剂，目前在中美处于临床1b研究阶段。此前，VIC-1911在干细胞移植后预防移植物抗宿主病（GVHD）和白血病复发的临床研究中已初步展示良好的疗效。本次在ASCO大会上展示的是一项1期临床研究数据，旨在评估VIC-1911联合第三代EGFR-TKI奥希替尼治疗TKI耐药、EGFR突变的非小细胞肺癌（NSCLC）患者的效果。此项研究共入组了24例患者，剂量递增阶段入组了7例患者（150mg 4例，200mg 3例），未观察到剂量限制性毒性（DLT），后选择200mg作为2期推荐剂量（RP2D）。与VIC-1911相关的最常见不良反应为腹泻（52.3%）、白细胞减少（38.1%）、中性粒细胞减少（33.3%）和血小板减少（28.6%）。剂量扩展阶段入组了17例受试者。在总体可评价疗效的23例患者中，10例患者为未使用奥希替尼（T790m阴性8例，T790m阳性2例），13例患者为奥希替尼耐药。未使用奥希替尼患者的客观缓解率（ORR）为50%（5例部分缓解[PRs], T790m阴性=4，T790m阳性=1)，疾病控制率（DCR）为80%（3例病情稳定[SDs]）。对于奥希替尼耐药患者，ORR为0%，DCR为53.8%（7例SDs）。在疾病控制的患者中，66.7%（10/15）的患者在数据截止时仍在治疗中，中位随访时间为5.5个月，未达到中位缓解持续时间（DOR），6个月DOR率为50%。未使用奥希替尼和奥希替尼耐药患者的中位无进展生存期（PFS）分别为4.6个月和2.1个月，6个月无进展生存率分别为70.0%和38.5%。研究认为：VIC-1911联合奥希替尼在既往接受过治疗的EGFR突变的非小细胞肺癌患者中具有良好的耐受性，联合用药也显示出持续的抗肿瘤活性，这表明阻断极光激酶A/AURKA在延缓奥希替尼耐药出现方面具有潜力。JSI-1187：ERK抑制剂适应症：实体瘤JSI-1187是一款高选择性ERK激酶抑制剂，目前在中美处于临床1期研究阶段。本次在ASCO大会上展示的是JSI-1187治疗MAPK通路突变晚期实体瘤患者的1期临床研究数据。截至2023年12月23日，此研究共入组了26例患者，其中每日两次（BID）组23例，80mg每日一次（QD）组3例。QD组未发生DLT；BID 96和80 mg组分别发生1例DLT（1例黄斑水肿）和2例DLT（1例黄斑水肿和1例肺炎）。JSI-1187的16 mg ~96mg BID组最常见的不良反应为低白蛋白血症（69.6%）、皮疹（62.5%）和贫血（43.5%），而JSI-1187 80mg QD最常见的不良反应为皮疹（100%）、白细胞减少（100%）和中性粒细胞减少（66.7%）。JSI-1187的16 mg ~ 96mg BID组治疗最常见的3级相关不良反应为贫血（17.4%）和血小板减少（8.7%）。26例患者中有18例评估了肿瘤缓解情况，在16-96 mg BID组和80 mg QD组中的最佳的疗效均为SD，包括1例NRAS突变黑色素瘤患者在32mg BID治疗时肿瘤缩小29.8%和1例MEK1 K57N突变肺癌患者在72mg BID治疗时肿瘤缩小21.6%，其中一例肺癌患者治疗持续时间已达14个月。研究认为：总体来看，JSI-1187单药治疗晚期实体瘤患者耐受性良好，初步显示出抗肿瘤作用。目前的证据支持未来在MAPK突变肿瘤患者中探索JSI-1187单药或联合治疗的效果。本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

ASCO会议临床结果临床1期临床2期

2024-03-13

·BioBAY

研发动态丨捷思英达Aurora A激酶抑制剂VIC-1911片治疗乳腺癌获批中国临床

3月11日，BioBAY园内企业捷思英达宣布，其小分子创新药Aurora A抑制剂VIC-1911片通过国家药品监督管理局（NMPA）的新药临床研究申请审评，并收到临床批件（2024LP00592）。捷思英达本次获批开展Aurora A抑制剂VIC-1911单药/联合奥拉帕利治疗晚期乳腺癌的临床研究。据世卫组织旗下的国际癌症研究机构(IARC)发布的最新的癌症负担数据（GLOBOCAN 2022)显示，全球乳腺癌年新增病例超过229万，高据第二位，年死亡病例超过66万（第四位），临床需求高未满足。VIC-1911有望为乳腺癌患者提供更为持久、显著的治疗效果。在此之前，VIC-1911片已获得两项中国临床1期批件(2021LP02060及2022LP00790)，批准适应症分别为与紫杉醇联合治疗晚期卵巢癌、输卵管癌和原发性腹膜癌，以及与奥希替尼联用治疗晚期非小细胞肺癌。此次IND获批是NMPA批准的第三项VIC-1911临床研究，也是地产化产品首次获批中国临床。地产化的成功保证了药品供应链的稳定，为开展更广泛、深入的临床开发提供了有力的支持。VIC-1911是新一代、高选择性、细胞周期调节激酶Aurora A抑制剂，美国临床I/II期开发阶段。VIC-1911已经率先在临床上被证明没有明显的骨髓抑制毒副作用。目前临床开发处于国际领先位置，具备国际首创潜力。捷思英达是一家聚焦肿瘤精准治疗新药研发生物医药企业，以临床需求和最新转化医学研究成果为驱动，致力于原创新药研发。资深和国际化高管团队在职业生涯中已经在中美开发成功20多款上市新药。捷思英达和国内外最权威的临床医生和研究机构合作，开展国际前沿水平的转化医学研究和临床研究，主要临床开发方向包括RAS基因突变的抗癌新药研发；克服EGFR抑制剂和KRAS抑制剂等靶向药的耐药研究；预防异基因造血干细胞移植后GVHD和白血病复发的研究；合成致死和药物联用策略的研究，目前已有三个产品进入或者即将进入临床2期研究阶段。▌文章来源：捷思英达责编：赵家帅审核：任旭推荐阅读研发动态丨星锐医药：呼吸道合胞病毒RSV mRNA疫苗STR-V003获美国FDA临床试验许可研发动态丨创澜生物：随机式、高通量全自动分子诊断系统GenMax 16全新上市研发动态丨映恩生物：靶向HER2的ADC拟纳入突破性治疗品种，针对子宫内膜癌

临床1期临床2期疫苗临床申请AACR会议

100 项与 TAS-119 相关的药物交易

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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
急性白血病	临床2期	美国	University of Minnesota Masonic Cancer Center	2022-03-17
移植物抗宿主病	临床2期	美国	University of Minnesota Masonic Cancer Center	2022-03-17
骨髓增生异常综合征	临床2期	美国	University of Minnesota Masonic Cancer Center	2022-03-17
骨髓增生性疾病	临床2期	美国	University of Minnesota Masonic Cancer Center	2022-03-17
非霍奇金淋巴瘤	临床2期	美国	University of Minnesota Masonic Cancer Center	2022-03-17
晚期肝细胞癌	临床1期	中国	捷思英达医药技术（上海）有限公司	2023-12-18
KRAS G12C突变非小细胞肺癌	临床1期	美国	VITRAC Therapeutics, LLC	2022-11-09
晚期非小细胞肺癌	临床1期	中国	-	2022-09-21
EGFR突变的非小细胞肺癌	临床1期	中国	-	2022-09-21
乳腺癌	临床1期	美国	捷思英达医药技术（上海）有限公司	2022-01-30

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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


NCT05120570 (4925, CTgov)	临床1/2期	骨髓增生性疾病 \| 非霍奇金淋巴瘤 \| 急性白血病 ... 更多	16	VIC- 1911	衊製鏇簾遞鬱鹹糧窪繭 = 顧膚選膚鏇艱遞餘淵艱鹹鹹積齋選膚艱範蓋築 (齋鬱鏇壓艱餘鹹簾窪齋, 網蓋淵餘鹽製齋繭選醖 ~ 夢糧鹽願窪鑰廠窪餘願)	-	2025-12-22
NCT05374538 (CTgov)	临床1期	KRAS G12C突变非小细胞肺癌	3	VIC-1911 (Dose Escalation Phase, Cohort 1a: VIC-1911 Monotherapy)	醖鏇襯齋築構繭鏇壓窪 = 築餘蓋鑰鹽簾製繭餘艱淵網淵艱鹽鬱鏇願簾獵 (壓製艱顧鬱廠範鬱衊簾, 築餘簾願淵夢蓋淵繭獵 ~ 廠餘膚憲糧壓範構壓鑰) 更多	-	2025-05-01
NCT05374538 (CTgov)	临床1期	KRAS G12C突变非小细胞肺癌	3	VIC-1911+sotorasib (Dose Escalation Phase, Cohort 1b: VIC-1911 Plus Sotorasib Combination Therapy)	醖鏇襯齋築構繭鏇壓窪 = 壓獵憲積襯襯顧淵築餘淵網淵艱鹽鬱鏇願簾獵 (壓製艱顧鬱廠範鬱衊簾, 鑰顧夢遞願選衊鹹顧齋 ~ 簾鑰製築積窪遞淵積淵) 更多	-	2025-05-01
NCT05489731 (ASCO2024) 人工标引	临床1期	EGFR突变的非小细胞肺癌 EGFR Mutation	24	VIC-1911 150mgosimertinib	鬱顧簾獵餘醖遞廠獵繭(構遞鏇選繭艱製繭齋蓋) = No observed 鹽積積憲廠糧鬱憲網壓 (壓齋窪構夢艱壓顧鑰構 ) 更多	积极	2024-05-24
NCT05489731 (ASCO2024) 人工标引	临床1期	EGFR突变的非小细胞肺癌 EGFR Mutation	24	VIC-1911VIC-1911 150mgosimertinib0mg or 200mg BID + osimertinib 80 mg QD (osimertinib-naïve)		积极	2024-05-24
NCT02134067 (ASCO 12019 \| ASCO 22019) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	26	paclitaxel+TAS-119	願鑰獵構觸壓繭膚觸壓(鏇簾製壓艱憲鹹願願選) = diarrhea, nausea, and fatigue (most ≤Gr2) 糧鹽顧憲蓋壓衊餘顧遞 (窪蓋襯憲範觸齋鑰憲願 ) 更多	积极	2019-06-01
NCT02448589 (ASCO2019)	临床1期	HR阳性/HER2低表达实体瘤	74	TAS-119	築繭窪鑰蓋艱淵顧顧憲(衊選獵製遞顧遞簾艱鹽) = Grade 3 ocular toxicity in 1 pt (300 mg cohort) 艱窪遞築襯繭窪壓簾繭 (糧積遞獵選顧獵鏇觸餘 ) 更多	不佳	2019-05-26