Phase I/Ib study with the combination of RMC-4630 and LY3214996 in metastatic KRAS mutant CRC, PDAC and NSCLC - The SHERPA-trial - Phase I/Ib study with the combination of RMC-4630 and LY3214996

开始日期2022-03-31

申办/合作机构-

NCT04916236

/ Terminated临床1期IIT

Phase I/Ib Study With the Combination of RMC-4630 (SHP2 Inhibitor) and LY3214996 (ERK Inhibitor) in Metastatic KRAS Mutant CRC, PDAC and NSCLC

This is a Phase I/Ib study in which the safety of the combination therapy of RMC-4630 and LY3214996 in the treatment of KRAS mutant cancers will be studied.

开始日期2022-03-31

申办/合作机构

Netherlands Cancer Insitute

[+1]

NCT04616183

/ Active, not recruiting临床1/2期IIT

Open-Label Phase 1b/2 Study of Cetuximab Administered in Combination With LY3214996 (ERK 1/2 Inhibitor) or Cetuximab in Combination With LY3214996 and Abemaciclib in Patients With Metastatic, Anti-EGFR-Refractory Colorectal Cancer

This phase Ib/II trial investigates the side effects and best dose of LY3214996 when given together with cetuximab alone or in combination with abemaciclib and to see how well they work in treating patients with colorectal cancer that cannot be removed by surgery (unresectable) and/or has spread to other places in the body (metastatic). Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. LY3214996 and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving LY3214996 and cetuximab alone or in combination with abemaciclib may help treat patients with colorectal cancer.

开始日期2020-12-02

申办/合作机构

The University of Texas MD Anderson Cancer Center

[+1]

100 项与 Temuterkib 相关的临床结果

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100 项与 Temuterkib 相关的转化医学

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100 项与 Temuterkib 相关的专利（医药）

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项与 Temuterkib 相关的文献（医药）

2025-10-01·Cancer research communications

RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types

Article

作者: Silvers, Thomas ; Fox, Raymond G. ; Davoudi, Zahra ; Teicher, Beverly A. ; Juneja, Poorva ; Morris, Joel ; Coussens, Nathan P. ; Dexheimer, Thomas S. ; Hollingshead, Melinda G. ; Takebe, Naoko ; Doroshow, James H. ; Kemp, Samantha B.

Abstract:

The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene is among the most frequently altered genes in cancer, and the KRAS protein was long deemed undruggable. Recent strategies to target oncogenic KRAS have included both direct inhibition of the KRAS protein and indirect inhibition of its activity by targeting upstream and downstream signaling pathway mediators. A high-throughput screen of multicell-type tumor spheroids was designed to identify active combinations of targeted small molecules and KRAS pathway inhibitors. Inhibitors of the nonreceptor protein tyrosine phosphatase Src homology 2 domain–containing protein tyrosine phosphatase (SHP2) and the guanine nucleotide exchange factor Son of Sevenless homolog 1 (SOS1) were tested to evaluate indirect upstream pathway inhibition, whereas sotorasib directly inhibited the KRAS G12C variant. As single agents, sotorasib and the SHP2 inhibitor batoprotafib (TNO155) exhibited selectivity toward spheroids with KRAS G12C, whereas the SOS1 inhibitor BI-3406 showed varying activity across KRAS variants. Vertical inhibition of the rat sarcoma virus (RAS)/MEK/ERK pathway by targeting SHP2 or SOS1 and the downstream kinases MEK (trametinib) or ERK (temuterkib) was highly effective. Inhibition of upstream tyrosine receptor kinases with nintedanib in combination with batoprotafib or BI-3406 was also effective and, in combination with sotorasib, demonstrated synergy in spheroids harboring KRAS G12C. Dual inhibition of the RAS/MEK/ERK and PI3K/Ak strain transforming (AKT)/mTOR pathways by batoprotafib or sotorasib with either the mTORC1/2 inhibitor sapanisertib or the AKT inhibitor ipatasertib demonstrated combination activity, primarily in spheroids harboring KRAS G12C. The BCL-2 inhibitor venetoclax, in combination with sotorasib, batoprotafib, or BI-3406, resulted in additive and synergistic cytotoxicity. Lastly, concurrent inhibition of the KRAS pathway with sotorasib and batoprotafib demonstrated combination activity in spheroids containing KRAS G12C.

Significance::

KRAS variants are oncogenic drivers for a range of human cancers. Multiple combinations of small-molecule agents that target RAS signaling were screened and reduced the viability of multicell-type tumor spheroids from a variety of human solid tumors. Combinations warranting further testing were identified.

2025-10-01·JACC: CardioOncology

Inhibition, But Not Depletion, of Erk Signaling Ameliorates Anthracycline-Induced Cardiotoxicity in Zebrafish

Article

作者: Ma, Xueling ; Moossavi, Maryam ; Mondaca-Ruff, David ; Ding, Yonghe ; Yan, Feixiang ; Xu, Xiaolei ; Zhu, Ping

BACKGROUND:

Anthracycline-induced cardiotoxicity (AIC) is a unique type of cardiomyopathy that limits the clinical use of anthracyclines in cancer therapy. Although several cardiomyopathy-related pathways have been identified, including extracellular signal-regulated kinase (ERK) signaling, pathway-specific interventions for AIC remain unclear.

OBJECTIVES:

The aim of this study was to investigate the role of Erk signaling in AIC using zebrafish genetics.

METHODS:

A zebrafish model of AIC was used to screen genes in known cardiomyopathy pathways, including Erk signaling. Heterozygous and homozygous mutants were evaluated for their modifying effects on AIC. In parallel, pharmacologic studies with ERK inhibitors were conducted to assess dose-dependent therapeutic effects of Erk inhibition.

RESULTS:

mek1^+/- and erk1^+/- mutants conferred protective effects in adult zebrafish with AIC. Consistent with this, Erk phosphorylation was aberrantly elevated in AIC hearts. Although heterozygous mutants mitigated AIC phenotypes, homozygous erk1^-/- mutants caused cardiac dysfunction and worsened AIC. Similarly, pharmacologic inhibition of Erk with temuterkib was therapeutic at low doses but induced dose-dependent cardiotoxicity. Mechanistically, the AIC model exhibited accelerated cardiac senescence, which can be attenuated by Erk inhibition.

CONCLUSIONS:

Aberrant Erk activation contributes to AIC, and controlled Erk inhibition may offer therapeutic benefit, potentially via antiaging mechanisms. However, optimization is essential, as excessive inhibition can be cardiotoxic.

2025-09-01·JCO Precision Oncology

Open-Label, Phase II Trial of Extracellular Regulated Kinase Inhibition Alone and in Combination With Autophagy Inhibition in Patients With Metastatic Pancreatic Cancer.

Article

作者: Parikh, Aparna R ; Bockorny, Bruno ; Wolpin, Brian M ; Enzinger, Andrea ; Bullock, Andrea ; Mancias, Joseph D ; Zheng, Hui ; Aguirre, Andrew J ; Zerillo, Jessica ; Bird, Alexandra ; Mayer, Robert J ; Brais, Lauren K ; Weekes, Colin D ; Ritterband, Lauren ; Ng, Kimmie ; Der, Channing J ; Rubinson, Douglas A ; Sanoff, Hanna K ; Slater, Sarah ; Whooley, Peter ; Wang, Junning ; Biller, Leah H ; Surana, Rishi ; Coleman, Emma C ; Graham, Christopher ; Bryant, Kirsten L ; Singh, Harshabad ; Perez, Kimberly ; Enzinger, Peter ; Somasundaram, Ashwin ; Williams, Hannah L ; Cleary, James M ; Morgado, Micaela ; Patel, Anuj K ; Raghavan, Srivatsan ; Huffman, Brandon M ; Clark, Jeffrey W ; Nowak, Jonathan O ; McCleary, Nadine J ; Saxena, Neetu ; Peters, Mary Linton ; Yurgelun, Matthew B ; Abrams, Thomas A ; Sawin, Mark

PURPOSE:

Oncogenic mutations in Kirsten rat sarcoma virus are present in over 90% of pancreatic ductal adenocarcinomas (PDACs). Preclinical data suggest that PDAC cells treated with inhibitors of the mitogen-activated protein kinase pathway demonstrate elevated autophagic flux. In this study, we evaluate the clinical efficacy of combining LY3214996 (extracellular regulated kinase inhibitor) with hydroxychloroquine (HCQ; autophagy inhibitor) in patients with metastatic PDAC.

METHODS:

Eligible patients had metastatic PDAC and at least one, but no more than two prior lines of systemic therapy. A safety lead-in evaluating the combination was conducted and the maximum tolerated dose level of LY3214996 was identified. Patients were then randomly assigned in a 1:1 fashion to receive either LY3214996 200 mg orally (PO) once daily + HCQ 600 mg PO twice a day (arm 1) or LY3214996 400 mg PO once daily (arm 2). The primary end point for this study was disease control rate (DCR). Secondary end points included overall survival (OS) and progression-free survival (PFS).

RESULTS:

Thirty-nine patients enrolled (20 in arm 1, 19 in arm 2). The DCR rates were 5% in arm 1 and 5.3% in arm 2. The median OS was 2.4 months in arm 1 (95% CI, 1.3 to 5.8) and 4.6 months in arm 2 (95% CI, 3.1 to 5.7). The median PFS was 1.3 months in arm 1 (95% CI, 0.8 to 1.8) and 1.9 months in arm 2 (95% CI, 1.644 to 2.4). The most frequently observed toxicities in both arms included nausea, diarrhea, elevated creatine phosphokinase, anorexia, and cytopenias. Exploratory analysis using patient-derived PDAC organoids did not show evidence of synergistic antiproliferative activity of LY3214996 in combination with chloroquine.

CONCLUSION:

LY3214996 alone or in combination with HCQ did not result in clinical activity in patients with metastatic PDAC.

项与 Temuterkib 相关的新闻（医药）

2022-12-10

·生物制药小编

赛诺菲为何放弃价值5亿美元的SHP2抑制剂合作？

12月7日，Revolution Medicines宣布，赛诺菲方面已发出通知，将终止双方从2018年开始价值5亿美元的SHP2抑制剂的开发和商业化合作。而协议终止后，Revolution Medicines将重新获得赛诺菲根据协议获得的所有全球权利，包括关于研发的决策权，以及RMC-4630的所有商业收益权。据悉，赛诺菲的发言人声称，终止其与RM公司的商业伙伴关系的决定是在“最近的投资组合审查和优先排序”之后做出的。受到这一消息影响，Revolution Medicines公司的股价短时间出现一波近14%的大幅跳水，随后才逐渐反弹。而赛诺菲方面的股价也有所波动，在7日和8日接连小幅下滑。这样一看，市场方面似乎更肯定了赛诺菲方面的说法，是因为战略布局而做出了取舍。那么从现有事实来看，赛诺菲方面的说法可信吗？这可以先从赛诺菲对RMC-4630的临床开发来看以及SHP2靶点的作用机理来看。SHP2靶点的作用机理与临床开发方式作为一种非受体蛋白酪氨酸磷酸酶，SHP2在受生长因子、细胞因子和整合素受体调节的细胞信号转导下游发挥重要作用，并参与包括细胞存活、增殖和迁移在内的细胞过程。首先，越来越多的证据表明，SHP2参与了癌细胞中的许多信号级联，包括RAS-MAPK、PI3K-AKT和JAK-STAT通路。对于PD1-PDL1通路的影响也在研究中。其次，Th1免疫能力的恢复和T细胞的激活也依赖于SHP2的抑制，Th1免疫能力的恢复和T细胞的激活能够激活肿瘤微环境内的免疫反应。再次，通过对SHP2的药理抑制可以增强CD8+ 细胞毒性T细胞介导的抗肿瘤免疫来降低肿瘤负担。最后，SHP2的过度激活突变已在努南综合征和各种类型的癌症中被发现，包括白血病、非小细胞肺癌(NSCLC)、胃食管癌和乳腺癌。因此，SHP2被认为是癌症治疗的潜在治疗靶点。尽管如此，SHP2这一靶点最初被认为是难以成药的，最初的几项靶向药物（如PTP结合位点的传统抑制剂，如PHPS1、GS-493和NSC-87877）普遍存在细胞渗透性低和生物利用度差的问题。，但后来通过蛋白变构和高通量筛选得到的SHP2变构抑制剂通过变构机制稳定了自抑制构象，更重要的是，变构抑制剂和其他激酶抑制剂的联合应用可以协同降低耐药的可能性。而目前，临床上较为前列的SHP2抑制剂包括诺华的TNO155、RMC-4630、加科思的JAB-3068和JAB-3312。其中JAB-3068已获得孤儿药认证。这些药物许多都采用了联合治疗的策略。以RMC-4630的临床开发策略为例，RMC-4630由于其在RAS-MAPK通路上的作用，因此可以与Amgen全球首个上市的KRAS G12C抑制剂Sotorasib（AMG510），以及另外一款KRAS G12C抑制剂Adagrasib联用。与Sotorasi初步的临床结果则表明疗效限制，且安全可控：在纳入的11例非小细胞肺癌患者中：3例（27%）有确认部分缓解；7例（64%）疾病控制（部分缓解+疾病稳定）。在接受最高剂量RMC-4630联合治疗的4例未经KRAS靶向治疗的非小细胞肺癌患者中：3例（75%）确认部分缓解，其中2例仍在持续缓解，4例（100%）疾病控制。有1例患者在既往索托雷赛治疗后疾病进展，在联合RMC-4630治疗5.5个月后肿瘤缩小超30%，治疗6.9个月时疾病进展。安全性方面，没有任何患者出现≥4级治疗相关不良事件。还有文献表明，MEK抑制剂似乎是SHP2抑制剂的“好伙伴”，在动物体内，SHP2抑制剂在KRAS突变的NSCLC同样可以导致肿瘤细胞衰老效应，这种效应能够被MEK抑制剂增强。因此RMC-4630能够与罗氏的MEK抑制剂Cobimetinib联用。而除此之外，RMC-4630还与LY3214996（ERK抑制剂），Osimertinib（第三代EGFR抑制剂），K药（PD-1抑制剂）等诸多药物展开临床应用。从合作内容和临床试验的举办者来看，这些广泛展开的临床主要由赛诺菲推动，但这样一看，临床开展的是不是太多了？毕竟许多临床研究也只是联合用药的探索……推测笔者推测，如果以赛诺菲的角度来看，虽说Sotorasib与RMC-4630的联用展现出了较好的初步效果，但从另外一个方面来看，拓展临床太多也可能造成太高花费。如果将5亿美元与如此多的临床项目相比，这样做似乎让赛诺菲本身承担了太多风险，而赛诺菲将这个“球”扔还给了RM。毕竟再怎么说，赛诺菲的肿瘤业务也不是主营业务。参考来源：OA03.03 Sotorasib in Combination with RMC-4630, a SHP2 Inhibitor, in KRAS p.G12C-Mutated NSCLC and Other Solid TumorsSong Z, Wang M, Ge Y, Chen XP, Xu Z, Sun Y, Xiong XF. Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies. Acta Pharm Sin B. 2021 Jan;11(1):13-29. doi: 10.1016/j.apsb.2020.07.010. Epub 2020 Jul 26. PMID: 33532178; PMCID: PMC7838030.Mainardi, S., Mulero-Sánchez, A., Prahallad, A. et al. SHP2 is required for growth of KRAS-mutant non-small-cell lung cancer in vivo. Nat Med 24, 961–967 (2018). https://doi.org/10.1038/s41591-018-0023-9免责声明：以上内容仅供参考，不构成任何投资建议和医学建议

孤儿药临床1期免疫疗法

2022-09-17

·药智网

【药咖君】19款1类新药获批临床，多款First-in-class新药国内获批临床！礼来、诺华、步长…

看点：1.37项新药申请获得临床试验默认许可，包括19款1类新药2.CDE新受理30个新药（53个受理号）的临床试验申请3.礼来重磅降糖药Tirzepatide减肥适应症在国内获批临床4.两款干细胞疗法进入临床阶段药智数据显示，本期（9月9日至9月16日）有37项新药申请获得临床试验默认许可，涉及13款国产新药，10款进口新药；另有30个品种（53个受理号）临床申请获CDE承办受理，更多动态如下：新药临床申请·新获批本期，37项新药申请获得临床试验默认许可，涉及13款国产新药，10款进口新药。获批临床的创新药涉及多款小分子创新药、单抗、双抗、融合蛋白、干细胞疗法等，适应症涵盖多种肿瘤、疼痛、黄斑变性、细菌感染、心肌梗死、脑卒中、自身免疫性疾病、血友病、帕金森病、肥胖等。数据来源：药智数据1. STC007注射液该药是阳光诺和子公司诺和晟泰通过应用计算机辅助药物分子设计(CADD)与经验分子结构改造(SAR)相结合手段，开发的一款化学1类新药，拟用于治疗术后疼痛。STC007注射液对κ阿片样物质(KOR)受体具有较强结合力，且在3种啮齿类动物疼痛模型中表现出良好的镇痛效果，毒理学研究中未见明显的不良反应，展现了良好的成药性和安全性，且无明显成瘾性风险。2. RG002片该药是凌济生物开发的新一代抗肝胆肿瘤耐药新药泛FGFR1-4 不可逆抑制剂，拟用于恶性肿瘤的治疗，包括但不限于伴有FGF/FGFR基因改变的晚期胆管癌、肝细胞癌、尿路上皮癌等。3. BGC1201片该药是博瑞医药开发的一款小分子创新药，拟用于晚期实体瘤的治疗。此次为该项目首次获批临床。据悉，BGC1201是 RTK-RAS-MAPK 信号通路靶向药物，兼具靶向肿瘤生长和肿瘤免疫的双重机制，BGC1201对 RAS-ERK 信号通路有调控作用，在调节肿瘤细胞存活和生长中发挥重要作用。此外，BGC1201作用位点处于PD1等免疫检查点下游，介导肿瘤免疫逃逸信号。4. YZJ-4729酒石酸盐注射液该药是扬子江药业全资子公司上海海雁医药开发的一款1类小分子创新药，靶点未知，本次获批临床，拟用于需要使用静脉注射阿片类药物的成人患者急性疼痛。药智数据显示，目前海雁医药申报临床1类新药已有7款，包括YZJ-0318 马来酸盐片、YZJ-0673马来酸盐片、YZJ-1495盐酸盐胶囊、YZJ-2440马来酸盐片、YZJ-3058片、YZJ-5053片以及YZJ-4729酒石酸盐注射液。5. EVER001胶囊 EVER001（又名XNW1011）是信诺维自主研发的新一代共价可逆的BTK抑制剂。2021年9月，信诺维、中国抗体制药与云顶新耀宣布达成全球独家合作协议，将XNW1011（SN1011）全球范围的肾脏疾病领域开发和商业化的权利授权给云顶新耀。本次EVER001胶囊获批临床适应症为以蛋白尿为特征的肾小球疾病。6. Tinlarebant 片 Tinlarebant (LBS-008) 是倍亮生技的主要候选产品，是一种口服的非维甲酸类 RBP4 小分子拮抗剂，每日口服一次，可以减少和维持维生素A（视黄醇）向眼睛的输送，以减少有毒维生素A副产物在眼组织中的积累。LBS-008曾获得FDA授予孤儿药认证（ODD）、儿科罕见疾病认证（RPD），快速审查认定，以及欧盟EMA授予的ODD。本次Tinlarebant在国内获批开展临床试验，用于治疗青少年遗传性黄斑变性疾病（Stargardt 病）。7. 注射用XNW4107 该药是信诺维医药开发的新一代β-内酰胺酶类广谱抗耐药菌药物，专门针对细菌耐药挑战而设计。本次批准开展3期临床，拟开发与亚胺培南/西司他丁钠联合用于革兰阴性菌引起的医院获得性细菌性肺炎（HABP）和呼吸机相关性细菌性肺炎（VABP）。值得一提的是，今年4月该3期临床方案也已获得美国FDA批准。此前XNW4107还曾获得FDA授予的合格传染病产品资格（QIDP）和快速通道资格。8. 注射用ZKLJ02 该药是龙津药业开发的一款化学1类创新药，本次获批临床，用于急性缺血性脑卒中，改善神经功能缺损。9. BC008-1A注射液该药是步长制药开发的一款特异性靶向 PD-1 和 TIGIT 的双抗药物，目前国内外尚无同类双靶点药物批准上市。本次获得临床试验默示许可，适应症为晚期实体瘤。这是继HER2/CD3双抗注射液BC004后，步长制药今年第二款步入临床阶段的创新生物药。10. 伊立珠单抗注射液伊立珠单抗（Itolizumab）是由Biocon Biopharmaceuticals开发的一款全球首创CD6单克隆抗体药物。该药已于2013年在印度获批上市，并先后于2013年和2020年获批银屑病和新冠病毒适应症。百泰生物目前已提交3项针对伊立珠单抗的临床申请，均获得临床默认许可，适应症分别为：急性移植物抗宿主病、病毒性肺炎引发的中重度急性呼吸窘迫综合征、合并间质性肺病抗MDA5抗体阳性皮肌炎。11. RY_SW01细胞注射液该药是由睿源生物申报的一款异体间充质干细胞药物，拟开发治疗活动性狼疮肾炎。今年6月，睿源生物与江苏省人民医院合作的“注射用人脐带间充质干细胞（hUC-MSCs）治疗难治性狼疮肾炎的安全性、耐受性、疗效探索的单中心临床研究”临床试验已在江苏省人民医院完成首例受试患者给药入组，初步结果显示，RY_SW01细胞注射液具有良好的安全性。12. 人脐带间充质干细胞注射液该药是上海泉生生物开发的一款人脐带间充质干细胞产品，研发代号ASCP04。目前已有3项适应症获得临床默认许可，分别为，轻至中度急性呼吸窘迫综合征（ARDS），强直性脊柱炎，Ⅱ度烧伤，还有一项临床试验申请尚在审评审批中。13. TNO155 该药是诺华开发的一款First-in-class选择性、变构、口服SHP2抑制剂，同时也是首个进入临床的SHP2抑制剂，是在高通量筛选出的先导化合物SHP836的基础上，进一步优化得到的，具有理想的成药性，例如：高渗透性、高溶解度、不抑制CYP450、理想的临床前PK参数。本次TNO155在国内获批临床，拟用于晚期实体瘤。14. LTT462 该药是诺华开发的一款ERK激酶抑制剂，目前全球尚无ERK激酶抑制剂获批上市，进展较快的项目包括BioMed Valley Discoveries开发的优立替尼、礼来开发的LY3214996、诺华开发的LTT462。15. TAK-981 注射液 TAK-981注射液（subasumstat）是武田制药开发的一款类泛素蛋白修饰小分子（SUMO）抑制剂。目前，TAK-981正在多种实体瘤和血液肿瘤中开展1/2期临床研究。在中国，该药曾获批在转移性或局部晚期实体肿瘤和血液系统恶性肿瘤成年患者中开展临床研究。本次该药获批临床的适应症为：联合利妥昔单抗用于治疗CD20阳性的复发/难治性非霍奇金淋巴瘤患者。16. BIIB122 BIIB122 (DNL151) 是一款潜在first-in-class的LRRK2小分子抑制剂，目前正在海外开展治疗帕金森病的3期临床试验。2020年，渤健与Denali Therapeutics达成一项超10亿美元的合作，从而获得合作开发和共同商业化BIIB122的权益。本次BIIB122在国内获批临床，适应症为用于治疗帕金森病。17. Selatogrel注射液该药是一种高效、高选择性、可逆的P2Y12受体拮抗剂，起效快，作用时间短。本在国内获得临床默认许可，拟用于有急性心肌梗死（AMI）病史的成人患者AMI的入院前治疗。18. TAR-200 该药由TARIS公司专有的膀胱癌新型靶向药物递送技术“TARIS技术”开发，可在膀胱内持续数周连续释放化疗药物吉西他滨。在美国，FDA已授予TAR-200快速通道资格，用于治疗不适合根治性疗法的肌肉浸润性膀胱癌（MIBC）患者。2019年12月，强生收购TARIS，将TAR-200收入囊中。本次TAR-200在中国获批开展临床试验，与强生的PD-1单抗Cetrelimab联用，适用于未接受过BCG治疗的高危非肌层浸润性膀胱癌患者的治疗。19. Tirzepatide注射液替尔泊肽（Tirzepatide）是一款GIP/GLP-1受体双重激动剂，是一款First-in-class药物，于2022年5月首次获FDA批准上市，用于治疗2型糖尿病。在中国，Tirzepatide注射液2型糖尿病适应症上市申请已于本月早些时候获得CDE受理。本次Tirzepatide注射液新适应症在国内获批临床，用于成人超重和肥胖者的药物干预治疗，降低其主要心血管事件的风险，减少2型糖尿病发生风险和改善肾脏结局。20. Modakafusp Alfa注射液 (TAK-573) TAK-573是武田制药与梯瓦（Teva）合作开发的一款潜在First-in-class免疫靶向减毒细胞因子。据悉，TAK-573不但能够直接杀死癌细胞，而且能够激活CD8阳性T细胞。此外，CD38的特异性和干扰素α2b分子与受体结合亲和力的减弱，显著降低了该产品脱靶结合风险和发生毒性的可能性。本次获批在国内开展多发性骨髓瘤（MM）适应症临床试验。新药临床申请·新受理本期，CDE新受理30新药（53个受理号）临床申请。其中，23个品种（39个受理号）为国产新药，7个品种（14个受理号）为进口新药，更多动态如下：数据来源：药智数据数据来源：药智数据、企业公告等网络公开数据信息来源：药智网、企业公告等网络公开信息注：药智网公众号【ID:yaozh008】后台回复【0918】，获取本文图表excel格式文档声明：本文观点仅代表作者本人，不代表药智网立场，欢迎在留言区交流补充；如需转载，请务必注明文章作者和来源。如涉及作品内容、版权和其它问题，请在本平台留言，我们将在第一时间删除。责任编辑 | 琉璃排版设计 | 惜姌媒体合作 | 17316793441（微信号：18323856316）投稿爆料 | 17783467842（同微信）转载授权 | 18523380183（同微信）发现“分享”和“赞”了吗，戳我看看吧

First in Class免疫疗法抗体小分子药物合作

2021-06-04

·GlobeNewswire

Ivy Brain Tumor Center Announces Interim Results from a Phase 0 ‘Trigger’ Trial of Targeted Combination Therapy for Glioblastoma

Phoenix, AZ, June 04, 2021 (GLOBE NEWSWIRE) -- The Ivy Brain Tumor Center at Barrow Neurological Institute, the largest early-phase drug development program for brain cancer in the world, has announced initial results from an ongoing, dual-drug Phase 0 study (NCT04391595) evaluating the tumor pharmacokinetics (PK) and tumor pharmacodynamics (PD) of abemaciclib, a selective CDK4/6-inhibitor, plus LY3214996, a selective ERK1/2 inhibitor, in recurrent glioblastoma patients.The results of this study were published online in the ASCO Meeting Library and will be presented on June 7, 2021 at the American Society of Clinical Oncology (ASCO) Virtual Annual Meeting during an oral abstract session on Central Nervous System Tumors.“Phase 0 studies are starkly underutilized in neuro-oncology. Over the last 50 years, only 22 publications examined drug pharmacodynamics and/or pharmacokinetics in glioblastoma patients,” said Nader Sanai, MD, director of the Ivy Brain Tumor Center and director of neurosurgical oncology at Barrow Neurological Institute. “Our strategy is to identify agents that tackle the roadblock of the blood-brain barrier and build upon those agents in drug combinations.”In this ongoing Phase 0 study, patients receive six days of abemaciclib in combination with LY3214996 leading up to a timed brain tumor resection following the final dose. To obtain the Optimal Time Interval (OTI) at which to capture PK/PD endpoints following the dosing of the drugs, patients were enrolled in two surgical time cohorts: 3-5 hours and 7-9 hours.PK and PD analyses are performed on the tumor tissue samples collected at the time of resection to measure the unbound concentration of each drug and its metabolites. If the minimum threshold for adequate and pharmacologically relevant penetration is met for both drugs, a ‘trigger’ is activated and the patient goes on to the Phase 2 component of the trial in which they receive the drug combination daily until progression.To date, 19 patients have enrolled in this Phase 0 clinical trial and six patients have advanced to Phase 2. Initial data suggests abemaciclib and LY3214996 achieve pharmacologically-relevant concentrations in Gd-non-enhancing GBM tissue and are associated with suppression of the RB pathway and tumor proliferation. Following six days of presurgical drug exposure, the OTI for tissue sampling was determined to be 3-5 hours after the final drug dose. Based on this interim analysis, the trial will accrue an additional 25 patients at this OTI.This study is funded by the Ben and Catherine Ivy Foundation, in partnership with the Barrow Neurological Foundation. Additional clinical trial information can be found at NCT04391595 or the Ivy Brain Tumor Center’s website.###About Ivy Brain Tumor CenterIvy Brain Tumor Center at the Barrow Neurological Institute in Phoenix, AZ is a non-profit translational research program that employs a bold, early-phase clinical trials strategy to identify new treatments for aggressive brain tumors, including glioblastoma. The Ivy Center’s Phase 0 clinical trials program is the largest of its kind in the world and enables personalized care in a fraction of the time and cost associated with traditional drug development. Unlike conventional clinical trials focusing on single drugs, its accelerated trials program tests therapeutic combinations matched to individual patients. Learn more at IvyBrainTumorCenter.org. Follow the Ivy Brain Tumor Center on Facebook, Instagram, Twitter and LinkedIn. Attachments

财报ASCO会议合作

100 项与 Temuterkib 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
非小细胞肺癌	临床2期	美国	Eli Lilly & Co.	2020-10-05
晚期癌症	临床2期	美国	Eli Lilly & Co.	2020-05-27
转移性胰腺癌	临床2期	美国	Eli Lilly & Co.	2020-05-27
急性髓性白血病	临床1期	美国	Eli Lilly & Co.	2020-07-15
多形性胶质母细胞瘤	临床1期	美国	Eli Lilly & Co.	2020-07-11
复发性胶质母细胞瘤	临床1期	美国	Eli Lilly & Co.	2020-07-11
慢性淋巴细胞白血病	临床1期	-	Eli Lilly & Co.	2020-02-03
套细胞淋巴瘤	临床1期	-	Eli Lilly & Co.	2020-02-03
边缘区B细胞淋巴瘤	临床1期	-	Eli Lilly & Co.	2020-02-03
巨球蛋白血症	临床1期	-	Eli Lilly & Co.	2020-02-03

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临床结果

适应症

分期

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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


NCT04386057 (CTgov)	临床2期	转移性胰腺癌 \| 晚期癌症	52	Hydroxychloroquine Sulfate+LY3214996 (LY3214996 and HCQ Combination)	糧廠願鹹鹽積範簾廠選 = 鏇齋鑰廠鹹構繭繭網衊製窪製膚願鑰憲壓製築 (構襯選餘願壓願網鹹鹽, 齋襯築選壓鹽廠鏇憲網 ~ 觸鹹廠選齋膚醖願餘選) 更多	-	2024-11-27
NCT04386057 (CTgov)	临床2期	转移性胰腺癌 \| 晚期癌症	52	LY3214996 (LY3214996-Monotherapy)	糧廠願鹹鹽積範簾廠選 = 範網網選窪鹹積網築獵製窪製膚願鑰憲壓製築 (構襯選餘願壓願網鹹鹽, 膚餘衊淵顧蓋鹹觸餘廠 ~ 艱積製構選鑰膚夢淵壓) 更多	-	2024-11-27
NCT04534283 (CTgov)	临床2期	肿瘤 \| 非小细胞肺癌	16	LY3214996+abemaciclib	網膚憲網選鑰觸鬱顧獵 = 窪簾鏇網艱夢積襯製簾壓範鹽簾鬱廠夢襯願獵 (構鏇遞廠壓顧鏇選壓膚, 顧廠鹽鑰遞糧鹹觸衊蓋 ~ 鏇鏇齋蓋顧觸鑰蓋願壓) 更多	-	2024-08-07
NCT04534283 (ASCO2023) 人工标引	临床2期	肿瘤 BRAF \| RAF1 \| MAP2K1 ... 更多	12	LY3214996+Abemaciclib	蓋鹹觸觸繭鏇鹹獵鬱蓋(膚淵築鹽鑰襯糧齋餘糧) = 醖醖鑰選餘窪網網鬱築鹽壓簾鏇遞簾積壓淵繭 (鹽願鹽餘鬱積鬱顧願鬱 ) 更多	积极	2023-05-31
NCT04391595 (DDRE-08, SNO2021)	早期临床1期	胶质母细胞瘤	-	LY3214996	廠觸淵願遞觸鹽觸築構(醖簾願遞襯齋鏇顧壓製) = 範鹹蓋構願襯積獵壓艱遞衊鹹窪願壓膚網鹽夢 (鏇繭齋築獵顧餘鏇憲膚 )	-	2021-11-12
NCT04391595 (DDRE-08, SNO2021)	早期临床1期	胶质母细胞瘤	-	Abemaciclib	廠觸淵願遞觸鹽觸築構(醖簾願遞襯齋鏇顧壓製) = 夢齋鏇顧襯蓋衊壓鬱夢遞衊鹹窪願壓膚網鹽夢 (鏇繭齋築獵顧餘鏇憲膚 )	-	2021-11-12
NCT02857270 (ASCO 12019 \| ASCO 22019) 人工标引	临床1期	晚期癌症	51	LY3214996	築簾鏇鹽蓋製構醖鬱壓(繭淵繭鬱衊糧築窪簾鹽) = grade (G) 3 cough and fatigue, G3 dehydration, increased creatinine (Cr), G3 increased CPK, G3 rash > 7 days, and 1 pt with renal failure. 製襯鏇鬱積積築憲壓製 (網積範構廠醖壓夢壓鹹 ) 更多	积极	2019-06-03
NCT02857270 (AACR2017)	临床1期	-	210	LY3214996	衊壓顧鬱鏇獵衊淵鹹鬱(獵壓製膚鏇窪鬱淵衊淵) = 淵選繭顧網膚淵觸艱糧積鬱選範醖鹹選廠觸淵 (淵觸壓製築窪簾構壓艱 )	-	2017-07-01
NCT02857270 (AACR2017)	临床1期	KRAS突变非小细胞肺癌	210	LY3214996 + Abemaciclib	衊遞艱壓選壓獵膚膚遞(繭艱衊簾夢網窪鹹窪鏇) = 鹹憲製願顧襯襯壓鹽簾夢構壓夢鏇襯鹽糧鹹齋 (衊範餘構簾鬱願衊鏇廠 )	积极	2017-07-01