Phase I Clinical Trial of CA-4948 (Emavusertib) in Combination With FOLFOX Plus Bevacizumab as Frontline Treatment in Patients With Metastatic Colorectal Cancer

This phase I trial studies the side effects and best dose of CA-4948 when given together with fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). CA-4948 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The chemotherapy drugs used in FOLOX, fluorouracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin is used with fluorouracil to treat colorectal cancer. Bevacizumab is in a class of medications called anti-angiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of the tumor. Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and/or effective in treating patients with metastatic colorectal cancer.

开始日期2025-06-23

申办/合作机构

National Cancer Institute

NCT07107750

/ Not yet recruiting临床1期IIT

Phase I Trial of CA-4948 in Combination With Cisplatin, Gemcitabine, and Durvalumab in Patients With Untreated Advanced or Metastatic Biliary Tract Cancer

Based on preclinical data from the Lim lab (WUSM), the investigators hypothesize that IRAK4 inhibition cripples tumor-intrinsic survival signaling and effectively overcomes the desmoplastic and immune-suppressive tumor microenvironment (TME) to render chemo- and immunotherapies effective in GI malignancy. Therefore, this trial is designed to evaluate the combination of CA-4948 and standard chemoimmunotherapy in untreated advanced or metastatic biliary tract cancer.

开始日期2025-10-31

申办/合作机构

Washington University School of Medicine

[+1]

NCT06439836

/ Recruiting临床1期IIT

Phase 1 Trial of CA-4948 in Combination With Pembrolizumab to Overcome Resistance to PD-1/PD-L1 Blockade in Metastatic Urothelial Cancer

This phase I trial tests the safety, side effects, best dose, and effectiveness of emavusertib (CA-4948) in combination with pembrolizumab in treating patients with urothelial cancer that has spread from where it first started to other places in the body (metastatic) and that has a resistance to PD-1/PD-L1 immune checkpoint inhibitors. CA-4948, a kinase inhibitor, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving CA-4948 in combination with pembrolizumab may be safe, tolerable and/or effective in treating patients with metastatic urothelial cancer that is resistant to PD-1/PD-L1 immune checkpoint inhibitors.

开始日期2025-05-05

申办/合作机构

National Cancer Institute

100 项与 Emavusertib 相关的临床结果

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100 项与 Emavusertib 相关的转化医学

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100 项与 Emavusertib 相关的专利（医药）

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项与 Emavusertib 相关的文献（医药）

2025-10-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of pyrrolo[2,3-d]pyrimidine derivatives as novel FLT3/IRAK4 inhibitors

Article

作者: Gao, Yue ; Wang, Peipei ; Yuan, Haibin ; Dong, Xiaowu ; Liu, Tao ; Li, Jia ; Zhou, Yubo ; Che, Jinxin ; Wang, Chenxi

Starting with the lead compound L-1, a series of pyrrolo[2,3-d]pyrimidine derivatives were developed as FLT3/IRAK4 inhibitors through three rounds of rational structural optimization. Among them, HB-29 had the remarkable activity towards FLT3-WT (IC₅₀ = 1.95 nM) and IRAK4 (IC₅₀ = 53.72 nM), outperforming the positive control, CA-4948. Besides, it exhibited excellent activities in MV4-11, MOLM3, and BaF3 cells with varying FLT3-TKD and FLT3-ITD-TKD mutations, highlighting its potential to overcome acquired resistance. The toxicity of HB-29 to normal bone marrow cell line HS-5 is relatively low (SI > 2000). Mechanistic studies revealed that HB-29 inhibited FLT3 and IRAK4 pathways in a dose-dependent manner, promoting cell apoptosis. Notably, in the cytokine-induced cell model, HB-29 efficiently induced apoptosis, and while also enhancing SOD activity and reducing ROS accumulation, thereby demonstrating its potential to overcome adaptive resistance. Moreover, HB-29 demonstrated an acceptable bioavailability (F = 13.4 %). These findings confirm that FLT3/IRAK4 inhibitor is a promising strategy for the treatment of AML.

2025-06-01·BRITISH JOURNAL OF HAEMATOLOGY

Contemporary management paradigms and emerging therapeutics for myelodysplastic syndromes/neoplasms

Review

作者: Xie, Yiyu ; Patel, Shyam A. ; Badar, Talha ; Zeidan, Amer M. ; Ramanathan, Ramkarthic

Summary:

From a historical perspective, the treatment landscape of myelodysplastic syndromes/neoplasms (MDS) has experienced a standstill in terms of new approvals by the U.S. Food and Drug Administration up until the recent 5 years. The widespread availability of comprehensive genome sequencing has shed insight into human MDS biology toward the goal of rational therapeutic design. This new knowledge has inspired the development of investigational therapies that extend beyond the scope of traditional erythropoiesis‐stimulating agents and hypomethylating agents. We describe how these contemporary treatment options are changing the management paradigms for lower‐risk and higher‐risk MDS, based on the landmark trial data. We discuss investigational therapies in the MDS pipeline, such as venetoclax, emavusertib, canakinumab and olutasidenib. We highlight challenges and solutions to the successful translation of emerging therapies based on our improved understanding of the biology of MDS, including the genomics of MDS with mutated TP53. We discuss how the identification of biomarkers of response to therapeutics may help guide clinical trial design for certain subsets of patients. Finally, we discuss how multicentre randomized trials can help facilitate the clinical rollout of emerging MDS therapeutics.

2025-05-01·Clinical Lymphoma Myeloma & Leukemia

Meeting Report From the 2024 Symposium on IRAK4 in Cancer: Highlights and Clinical Updates

Review

作者: Nayak, Lakshmi ; Metzeler, Klaus H ; Garcia-Manero, Guillermo ; Lim, Kian-Huat ; von Roemeling, Christina ; Doonan, Bently ; Ferreri, Andrés J M ; Tun, Han W ; Nowakowski, Grzegorz S ; Winer, Eric S ; Konopleva, Marina

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a serine/threonine kinase that mediates interleukin-1 and Toll-like receptor (TLR) signaling. IRAK4 drives the activation of nuclear factor kappa B (NF-κB), which promotes cell survival, inflammation, and proliferation. Aberrant activation of IRAK4 and TLR signaling has been implicated in multiple malignancies. At the 3rd Annual IRAK4 in Cancer Symposium, experts discussed the role of IRAK4 in cancer biology, the potential for synergism between IRAK4 inhibition and other treatments to overcome resistance, and how IRAK4 inhibition may improve clinical outcomes. Preclinical data were presented demonstrating the activity of IRAK4 inhibition alone or in combination with other anticancer agents in acute myeloid leukemia, myelodysplastic syndrome, non-Hodgkin lymphoma, primary central nervous system lymphoma, melanoma brain metastases, gastrointestinal cancers, and pancreatic ductal adenocarcinoma. Clinical data from the targeted small-molecule IRAK4 inhibitor emavusertib (CA-4948) were presented, including data from the TakeAim Leukemia and TakeAim Lymphoma trials of emavusertib in myeloid and lymphoid malignancies, respectively, and preliminary data from trials of emavusertib in multiple solid tumors. The meeting closed with expert discussion of the emerging profile of IRAK4 inhibition in cancers and the potential for IRAK4 inhibition to improve outcomes across both solid and liquid tumors.

项与 Emavusertib 相关的新闻（医药）

2025-08-25

·BioPlus

IRAK4，道路曲折，但前途光明

作者：十七前言丝氨酸/苏氨酸激酶IRAK4，参与的TLR/IL-1R信号通路极其复杂，涉及众多的上游受体和下游信号分子，在免疫信号传导和炎症反应中都有作用，其研究和药物开发过程中面临诸多挑战，但同时也展现出巨大的潜力和希望。早期的IRAK4抑制剂开发主要集中在小分子激酶抑制剂上，但这些抑制剂往往存在选择性不高、药代动力学特性不佳等问题。此外，IRAK4在免疫系统中的重要性也意味着药物开发需要在抑制炎症反应和避免过度免疫抑制之间找到平衡。过度抑制IRAK4可能导致免疫功能受损，增加感染风险，因此药物的安全性和有效性的平衡是开发过程中的关键挑战。但随着对IRAK4信号通路的深入理解以及不同药物类型开发如小分子和PROTACs药物等，给IRAK4研发带来希望。而且IRAK4适应症逐渐拓宽，包括化脓性汗腺炎（HS）、特应性皮炎（AD）、COPD、类风湿性关节炎、系统性红斑狼疮等自身免疫性疾病以及非霍奇金淋巴瘤（NHL）、弥漫大B细胞淋巴瘤（DLBCL）等肿瘤疾病，为患者提供新的治疗选择。 01 IRAK家族和信号通路 IRAK4属于IRAK家族（白细胞介素-1受体相关激酶家族），该家族还包括IRAK1、IRAK2和IRAK3（也称IRAK-M），IRAK家族成员均含有N端的死亡结构域（DD），用于蛋白间相互作用；中心的丝氨酸/苏氨酸激酶结构域（KD），用于磷酸化下游底物，除IRAK4外，其他成员还包含C末端结构域（图1）[1]。图1. IRAK4家族结构 IRAK4是一种丝氨酸/苏氨酸激酶，主要参与Toll样受体（TLR）和白细胞介素-1受体（IL-1R）介导的信号通路，IRAK4接收来自上游TLRs和IL-1R的信号，在免疫应答中被招募形成Myddosome复合物，激活下游的NF-κB、JNK等信号通路，调控炎症因子的表达。此外，IRAK4还参与调节NADPH氧化酶活性和p38 MAPK信号转导（图2）[2]。图2. IRAK4介导的信号通路 IRAK4的异常激活与多种疾病相关，如类风湿关节炎（RA）、系统性红斑狼疮（SLE）、特应性皮炎（AD）、慢性阻塞性肺病（COPD）、哮喘、银屑病等炎症性疾病。IRAK4在RA的发病机制中起重要作用。在滑膜液中，单核细胞/巨噬细胞上的TLR被内源性分子激活，诱导NF-κB分泌促炎因子，进而激活成纤维细胞样滑膜细胞（FLS）中的TLR-NF-κB信号通路，导致炎症和趋化因子的表达。而且，IRAK4在多种肿瘤中也高表达，如血液系统恶性肿瘤（如弥漫性大B细胞淋巴瘤）和实体瘤（如结肠癌、乳腺癌、肺癌等），通过调控肿瘤微环境中的炎症反应，影响肿瘤的发展（图3）。图3. IRAK4的发病机制目前尚无IRAK4靶向药获批上市，但临床上有很多在研的靶向IRAK4药物，包括小分子和PROTAC药物等。 02 在研的IRAK4小分子药物 IRAK4靶向药最初的药物开发类型多为小分子抑制剂，它们通过竞争性结合IRAK4的ATP结合口袋，抑制其激酶活性。辉瑞的Zimlovisertib是全球首个进入临床试验的IRAK4抑制剂，但因无法改善特应性皮炎患者皮肤微环境的炎症反应，于2022年8月终止开发，拜耳的Zabedosertib也因在特应性皮炎的Ⅱ期临床中疗效未能显著优于现有疗法，于2024年5月终止研发。此外，还有多款临床研究阶段IRAK4小分子抑制剂长期无动态或被终止（图4）。不过，IRAK4小分子抑制剂的研发一直在进行中，如吉利德的Edecesertib、Curis的Emavusertib、朗来科技的MY004567、阿斯利康的AZD6793和AZD2962等（图4）。图4. 在研的IRAK4小分子药物 1. Edecesertib Edecesertib（GS-5718）是一种强效、选择性的IRAK4抑制剂，具有良好的口服生物利用度和药代动力学特性。近期，Ammann等人在JMC杂志上报道了Edecesertib的结构与临床前数据。Edecesertib的结构如图5a所示。Edecesertib显示出对人血浆的中等结合能力（游离分数为4.4%），并且在人全血细胞实验中具有良好的活性（EC₅₀ = 124 nM）。该化合物具有良好的渗透性，在pH 2时溶解性良好，在pH 7时溶解性中等，并且在AMES实验中呈阴性。在激酶结合实验中（图5b），Edecesertib（测试浓度为1000 nM）显示出高选择性，只有七个激酶靶点（IRAK1、CDK7、CLK1、CLK2、CLK4、LRRK2、TAK1）的活性低于对照组的20%。 Edecesertib的初步毒理学研究在大鼠和食蟹猴中进行。大鼠的研究持续了14天，剂量水平为5/25/300 mg/kg/天；而食蟹猴的研究持续了7天，剂量水平为50/100/200 mg/kg/天。在这两项研究中，直到测试的最高剂量水平，均未观察到与药物相关的不良反应。令人欣慰的是，与体外hERG信号缺失一致，在食蟹猴研究中未观察到QT间期的剂量依赖性变化，这表明心血管毒性风险较低（见图5c）[3]。图5.Edecesertib的结构与临床前数据在类似人类狼疮的NZB/W小鼠模型中，Edecesertib显著降低了小鼠血清中TNFα和IL-12/23p40的水平，提高了小鼠存活率，并显著降低了蛋白尿水平（图6）。图6. Edecesertib在小鼠中疗效目前，Edecesertib正在进行针对系统性红斑狼疮（SLE）和皮肤红斑狼疮（CLE）的II期临床试验（图7）。图7. 吉利德炎症领域管线 2. Emavusertib Emavusertib（CA-4948）是由Aurigene Discovery原研的一款IRAK4小分子抑制剂，Curis通过与Aurigene的合作获得了Emavusertib的独家开发权。Curis目前负责Emavusertib的临床开发和商业化推进，主要用于治疗血液系统恶性肿瘤和某些实体瘤。在一项I期临床试验（NCT03328078）中，Emavusertib单药治疗在多种非霍奇金淋巴瘤患者中显示出一定的疗效，其中28例可评估患者中有8例（29%）肿瘤负荷减少≥20%（图8）[4]。图8. Emavusertib的临床试验结果在一项I期临床试验（NCT04278768）中，Emavusertib单药治疗在49例患者中进行了评估，其中包括急性髓系白血病（AML）和骨髓增生异常综合征（MDS）患者。在5例可评估的携带剪接体突变的AML患者中，40%达到完全缓解（CR）或血液学完全缓解（CRh）。在7例高危MDS患者中，57%达到骨髓CR。此外，在29例无SF3B1/U2AF1/FLT3突变的患者中，1例达到CR，2例达到PR（图9）。图9. Emavusertib的临床试验结果 2024年美国血液学会（ASH）年会上，Winer 等人报道了Emavusertib（CA948）在复发/难治性急性髓性白血病患者中的初步安全性和疗效。截至2024年7月10日，共有48例携带靶向突变（FLT3、U2AF1或SF3B1）且既往接受少于3线治疗的复发/难治性急性髓系白血病（R/R AML）患者接受了Emavusertib治疗。在200 mg BID队列中，5例可评估反应的患者中有1例携带FLT3突变且既往接受过HMA、VEN和FLT3i治疗的患者达到了形态学白血病无白血病状态（MLFS）。在300 mg BID队列中，有9例患者为反应者。在17例可评估反应的携带FLT3突变的患者中，有7例产生了反应：4例完全缓解（CR），1例部分血液学恢复的完全缓解（CRh），2例MLFS，治疗持续时间范围为85天至24天。在25例可评估反应的携带SF突变的患者中，有5例产生了反应：2例CR，2例不完全和部分血液学恢复的完全缓解（CRi/CRh），1例MLFS。2例CRi和CR的患者随后接受了干细胞移植。在9例反应者中，8例在1个治疗周期后产生反应；6例既往接受过VEN治疗；8例既往接受过HMA治疗；7例产生反应的携带FLT3突变的患者中有3例既往接受过FLT3i治疗。截至2024年7月10日，共有145例R/R AML（N=99）和高危骨髓增生异常综合征（hrMDS，N=46）患者接受了至少一次剂量的Emavusertib，剂量水平为200 mg至300 mg BID。治疗相关不良事件（TRAEs）≥3级在41例（28.3%）患者中报告，且大多数是可逆且可管理的[5]。 3. MY004567 MY004567是由上海美悦生物科技发展有限公司（朗来科技子公司）自主研发的1类新药，是一种IRAK4抑制剂，主要用于治疗自身免疫性疾病，如类风湿关节炎（RA）、银屑病和特应性皮炎等。 MY004567目前处于临床试验阶段，其研发进展顺利，多个适应症的临床试验正在进行中，包括MY004567片在中至重度活动性类风湿关节炎患者中的药代动力学研究、评估MY004567片单、多次给药在健康成年受试者中的安全性、耐受性和药代动力学特征的I期临床试验、MY004567片治疗中至重度活动性类风湿关节炎患者的II期临床试验、MY004567片在中至重度活动性类风湿关节炎患者中的药代动力学研究等（图10）。图10. MY004567的临床试验方案 03 在研的IRAK4的PROTAC药物 IRAK4小分子药物开发并不顺利，如上所述，多款药物被终止或无进展，因为IRAK4与MyD88、IRAK1等蛋白相互作用形成Myddosome复合体，该复合体在TLR/IL-1R介导的信号传导中起核心作用。IRAK4在该复合体中既具有激酶功能，也具有支架功能，传统小分子抑制剂仅能阻断激酶活性，无法干扰支架功能，难以全面抑制炎症信号通路，不足以产生有效的治疗效果。因此，很多药企纷纷开发IRAK4的PTOTAC药物，如KymeraTherapeutics的KT-474和KT-485、百济神州的BGB-45035、领泰生物的LT-002等。 1. KT-474和KT-485 KT-474是由KymeraTherapeutics研发的一种靶向IRAK4的PROTAC药物，通过泛素-蛋白酶体系统特异性地降解IRAK4蛋白，同时抑制其激酶活性和骨架功能。 2020年7月，Kymera Therapeutics与赛诺菲首次达成一项多项目战略合作协议，共同开发针对IRAK4靶点的“first-in-class”蛋白降解疗法，用于治疗免疫炎症疾病。根据协议，Kymera获得了1.5亿美元的前期付款，并有资格获得超过20亿美元的潜在里程碑付款。 Kymera与赛诺菲合作的首个成果就是KT-474，已推进至II期临床阶段，用于治疗化脓性汗腺炎（HS）和特应性皮炎（AD）。在临床前研究中，KT-474显示出强大的IRAK4降解能力，能够显著抑制多种炎症细胞因子的产生。在健康志愿者（HVs）中，KT-474显示出剂量依赖性的血浆暴露增加，稳态血浆浓度在第7天达到，第14天的暴露量比第1天增加了3-4倍。皮肤中的药物浓度显著高于血浆，且在停药2周后仍可检测到。在化脓性汗腺炎（HS）患者中，KT-474治疗28天后，IRAK4在皮肤病变中的降解率超过50%，且与健康志愿者的水平相当，在特应性皮炎（AD）患者中，KT-474治疗28天后，IRAK4在皮肤病变中的降解率超过50%，且与健康志愿者的水平相当（图12）图12. KT-474的临床前和临床数据然而，赛诺菲在2025年6月决定不再推进KT-474的开发，而是优先推进下一代口服IRAK4降解剂KT-485进入临床测试。KT-485在临床前测试中展示了更高的选择性和效力，并且具有良好的安全性。Kymera Therapeutics因此获得了2000万美元的临床前开发里程碑付款，并且未来有资格基于潜在临床开发、注册和商业化里程碑获得9.75亿美元的额外付款（图13）[6,7]。图13. 赛诺菲选择KT-485代替KT-474 2. BGB-45035 BGB-45035是百济神州基于自有CDAC平台上研发的第二款靶向降解剂，靶向IRAK4，用于治疗各类自身免疫性疾病。据报道，该药物具有潜力诱导更深、更快的IRAK4降解，并且细胞因子抑制作用更强。 2024年8月14日，据CDE官网显示，百济神州的BGB-45035片获得临床试验默示许可，适应症为中重度特应性皮炎。 2025年JPM会议上，百济神州提及BGB-45035为处于1期临床阶段的“高潜力”早期研发管线之一。百济神州认为BGB-45035将在自身免疫性疾病的治疗中发挥重要作用（图14）。图14. 2025年JPM会议上百济神州管线目前，BGB-45035已在一期临床试验中显示出显著的IRAK4降解特性，具有60-96小时的长半衰期。百济计划于2025年进行BGB-45035的2期临床试验，预计于2025年下半年获得组织IRAK4降解的概念验证数据（图15）。图15. 2025年下半年BGB-45035重大进展 3. LT-002 LT-002是由领泰生物基于其现有的靶向蛋白降解(Targeted Protein Degradation, TPD)新药研发平台Nano-SPUD®筛选得到的一款靶向IRAK4的PROTAC药物，是继Kymera的KT-474之后国内首创、全球第二的IRAK4靶向蛋白降解剂，主要用于治疗自身免疫性疾病，如化脓性汗腺炎和特异性皮炎等，已在临床前动物模型中显示出优越的改善皮肤炎症症状的疗效以及良好的安全性。 2024年6月25日，领泰宣布完成LT-002的1期临床试验的首例健康志愿者给药，该项试验覆盖全部120多例健康志愿者，通过单次剂量递增(SAD)和多次剂量递增(MAD)给药，旨在评价其在健康成年人中的的安全性、耐受性和药代动力学特征。根据目前的未揭盲数据显示，LT-002在全部健康志愿者中表现出良好的安全性和耐受性；同时，该药物在靶组织皮肤中的蓄积量较高，对于外周血单核细胞（PBMC）及皮肤中的IRAK4蛋白均具有显著的降解作用，分别能够达到99%和90%以上，并且呈现出明显的剂量依赖性；此外，LT-002还显著抑制了多个促炎细胞因子的释放，显示出其在抗炎方面的巨大潜力[8]。 2025年6月12日和7月9日，领泰相继宣布LT-002用于治疗特应性皮炎（AD）和化脓性汗腺炎（HS）的 IC 期临床试验已完成首例患者首次给药，该项目在临床开发中又一重要进展，标志着其多个适应症研究正式进入患者临床试验阶段。小结 IRAK4是一个药物研发热门靶点，小分子和PROTAC药物的研发层出不穷，尽管它们的开发都受到一些挫折，但新的方案和更优的药物仍在积极开发中。欢迎大家加入BioPlus微信交流群，共同探讨。 BioPlus 微信交流群申请入群申请联系人：Lisa 邮箱：lisa.li@bp-bioplus.com 电话：18662346610（同微信）入群申请，请先添加Lisa微信，并分享名片入群画像：Biotech/药厂研发/BD、投资机构、临床医生等入群福利：不定时行业资料包分享参考文献 1. Yifan Feng, Chengjuan Chen, Anqi Shao, Lei Wu, Haiyu Hu, Tiantai Zhang, Emerging interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitors or degraders as therapeutic agents for autoimmune diseases and cancer, Acta Pharmaceutica Sinica B 2024;14(12):5091e5105 2. Kymera: KT-474 HS and AD Clinical Data and Oncology Pipeline Update 3. Stephen E.Ammann, et.al, Discovery of Edecesertib(GS-5718): A Potent, Selective Inhibitor of IRAK4, J.Med.Chem.2025,68,10619−10630 4. Ricardo D. Parrondo et.al, IRAK-4 inhibition: emavusertib for the treatment of lymphoid and myeloid malignancies, Front. Immunol. 14:1239082. 5. Eric S. Winer et.al, Preliminary Safety, Efcacy , and Molecular Characterization of Emavusertib (CA948) in Relapsed/Refractory Acute Myeloid Leukemia Patients, Blood 144 (2024)737-739 6. Kymera snags Gilead as new partner, while Sanofi opts for next-gen IRAK4 degrader 7. Kymera: Revolutionizing Immunology with Oral Medicines June 2025 8. 领泰生物：Last HV Out！领泰生物宣布首个管线IRAK4降解剂的I期临床试验完成全部健康志愿者给药拓展阅读 BioPlus-海外寻找资产系列： 1.AACR复盘：9家CDH17-ADC数据对比 2.自免小众靶点APRIL，正在悄悄火起来了！ 3. STEAP1，会成为ADC与TCE的下一个爆款靶点么？ BioPlus国际大会跟踪系列： 1. 2025 ASCO：ADC、双抗/多抗，有哪些看点？（附一览表） 2. 2025 AACR 双抗与ADC有哪些看点？ 3. 小细胞肺癌领域，下一步将如何“破局”，ADC or TCE？ 4. ELCC 讨论：NSCLC的ADCs最新进展 5. 未来ADC发展方向：新靶点，新载荷，双靶点/双表位... 6. 2025 ASCO 重点项目临床数据：有哪些精彩看点？ 7. 2025 ASCO 重点项目临床数据 BioPlus靶点/管线研究系列： 1. “待爆”：CDH17 ADC项目大比拼，谁将脱颖而出? 2. PD-1激动剂在自免疾病项目数据盘点：失败项目的“坑”与启示 3. 上临床就能卖？DLL3 ADC这么好卖？ 4. 胰腺癌三大热门靶点：CLDN18.2、EGFR、RAS 5. TSLP/SCF双抗，下一个自免待爆靶点组合？ 6. GPC3靶点临床屡败，TCE能改写格局么？ 7. 亮相AACR，曾被临床终止的ADC靶点Ly6E，能否卷土重来？ 8. 最高18.45亿美元！赛诺菲为何重金买了两款TL1A双抗？ 9. 2025 Q1：BMS、Sanofi和Roche管线调整，哪些项目被砍？ 10. 现场！2025AACR：KRAS抑制剂的百花齐放 11. IL-17小分子抑制剂，能否杀出重围？ 12.全球首款：华东医药申报MUC17 ADC药物 13.荨麻疹 first-in-class双抗提交临床试验申请 14.绝非 “越低越好”：CD3 亲和力的权衡之道 15.重磅！罗氏披露BBB穿越Aβ药物最新临床数据（附详细资料） 16.阿斯利康C5纳米双抗：重症肌无力III期临床达主要终点 BioPlus技术平台深入剖析系列： 1. TCE 免疫共刺激信号之选：CD2，一颗冉冉升起的新星 2. BD爆发前夜！6家TCE Probody技术平台深度盘点 3. TCE Probody：Amgen携重磅技术“破局“，改写行业格局？ 4. 有人放弃，有人前行！自免TCE全球管线大盘点 5. Immunocore将TCR疗法照进现实，向自免疾病迈进 6. B细胞清除免疫重置：SLE等疾病长效缓解终成现实！ 7. 国内50家CD3平台序列来源汇总 8. CD28共刺激最终章？ZW209 DLL3/CD3/CD28 三抗剑指 Amgen 9. TCE 结构之争落幕：行业用行动给出 “标准答案” 10. CD3 VHH猴交叉：重要吗？ 11.Genentech创新前沿：口服VHH抗体，靶向IL-23R 12.AbbVie专利公开：靶向PSMA/STEAP1 双抗ADC BioPlus人物专访： 1. 专访肖亮：卖青苗不一定是坏事，这是中国Biotech长成参天大树的必经之路 2. 专访王刚，恺佧生物这些年的“出海”之旅？ 3.专访熊安稳教授：NSCLC，PD-1/VEGF之后，PD-1/IL2会是下一个双抗之王么？

蛋白降解靶向嵌合体上市批准

2025-07-02

·FiercePharma

China approves 4 new drugs, including a global first-in-class medicine

As the domestic biotech industry matures, China has given birth to increasingly more first-in-class drug assets, some of which have become sources for global innovation. China’s National Medical Products Administration (NMPA) has approved four new drugs developed by local biopharma companies, including a first-of-its-kind molecule in blood cancer.Wednesday, Chinese regulators announced (Chinese) the conditional approval of ifupinostat (BEBT-908) for treating diffuse large B-cell lymphoma (DLBCL) patients who have tried at least two prior lines of therapy.The drug, developed by BeBetter Med, is now the first HDAC/PI3K dual-targeted inhibitor approved anywhere, even though the U.S. FDA has approved multiple drugs separately targeting the two types of enzymes in blood cancers.Massachusetts-based Curis had previously been working on an HDAC/PI3K candidate called fimepinostat, which in 2018 earned an FDA “Fast Track” designation in third-line DLBCL. But the company shelved the program to put all its resources behind emavusertib, a potential first-in-class IRAK4 inhibitor, also in B-cell malignancies.A novel mechanism doesn’t necessarily mean better efficacy. In a pivotal phase 2b study, ifupinostat yielded an overall response rate (ORR) of 33.8%, according to BeBetter. After excluding patient loss to follow-up and protocol deviations caused by the COVID-19 pandemic, the ORR was 53.6%. But the number is lower than the roughly 70% posted by Gilead Sciences’ CD19 CAR-T therapy Yescarta in the Zuma-1 trial. Importantly, cross-trial comparisons come with intrinsic flaws such as differences in baseline patient characteristics.Nevertheless, ifupinostat delivered an adjusted 67% ORR in patients who had failed CAR-T and bispecific antibodies, according to BeBetter.Besides, as a small molecule drug, ifupinostat will be priced significantly cheaper than CAR-T and T-cell engagers, BeBetter noted.The company is conducting a confirmatory phase 3 trial to turn ifupinostat’s conditional nod into a full approval. The study is combining ifupinostat with rituximab in second-line DLBCL. In an exploratory phase 1b study, the combo achieved a 76.2% ORR as second-line treatment, according to results presented at this year’s American Society of Clinical Oncology meeting.As China's biotech industry matures, the country has given birth to an increasing number of first-in-class drug assets, some of which have become sources for global innovation. These include Akeso’s ivonesimab, which in 2024 became the world’s first approved PD-1xVEGF bispecific antibody thanks to a Chinese nod in EGFR-mutated nonsquamous non-small cell lung cancer.The PD-(L)1xVEGF mechanism gained prominence after ivonescimab’s phase 3 head-to-head success against Merck & Co.’s Keytruda in a Chinese population of patients with first-line NSCLC. Merck, Bristol Myers Squibb and Pfizer have since added to the fanfare with potential multibillion-dollar licensing deals all surrounding candidates developed in China. Also on Wednesday, the NMPA cleared China’s eighth CDK4/6 inhibitor, Betta Pharma’s tibremciclib, to be used alongside fulvestrant in HR-positive, HER2-negative breast cancer following progression on endocrine therapy. The drug has a similar structure to Eli Lilly’s Verzenio but with less inhibition of CDK9.In a China phase 3 trial, the addition of tibremciclib to fulvestrant led to a 69% reduction in the risk of progression or death compared with fulvestrant alone.In a third new cancer drug approval by NMPA, the agency greenlighted Simcere’s anti-VEGF antibody suvemcitug for use alongside chemotherapy for ovarian cancer patients who have tried no more than one line of therapy after developing resistance to platinum-based chemo.The drug proved its worth in a China phase 3 trial coded Scores carried out in patients with platinum-resistant ovarian cancer. Patients in the suvemcitug arm had a 54% lower chance of progression or death versus those in the placebo group, according to data released at least year’s ASCO meeting. Overall survival data were immature but favored the suvemcitug arm with a preliminary 21% death risk reduction.At that time, investigators noted that Scores was the first double-blinded phase 3 trial demonstrating the efficacy of an anti-angiogenic agent in platinum-resistant ovarian cancer. Outside of oncology, the NMPA cleared Changchun GeneScience Pharmaceutical’s firsekibart (formerly genakumab) for certain patients with acute gouty flares. To be eligible, patients must be unable to tolerate or respond to non-steroidal anti-inflammatory drugs and colchicine, and they must not be suitable to receive steroid hormones repeatedly.The drug blocks IL-1β, the same target of Novartis’ Ilaris, which secured its own gout flares nod from the U.S. FDA in 2023, making it the first biologic therapy in the indication. Ilaris is not approved in China.

临床结果临床3期临床2期免疫疗法上市批准

2025-06-17

·EINPresswire

The End Brain Cancer Initiative Partners with Curis to Pre-qualify for PCNSL TakeAim Lymphoma Clinical Trial

The End Brain Cancer Initiative Partners with Curis to Promote Awareness and Pre-qualify for PCNSL TakeAim Lymphoma Clinical Trial REDMOND, WA, UNITED STATES, June 16, 2025 / EINPresswire.com / -- FOR IMMEDIATE RELEASE Contact: Dellann Elliott Mydland, 425-785-8489, Dellann@EndBrainCancer.org The End Brain Cancer Initiative Partners with Curis to Promote Awareness and Pre-qualify for PCNSL TakeAim Lymphoma Clinical Trial The End Brain Cancer Initiative (EBCI) has partnered with Curis to promote awareness and pre-qualify patients for the company’s TakeAim Lymphoma Clinical Trial (CA-4948-101) clinical trial, an open-label, dose escalation and expansion trial of Emavusertib in Relapsed or Refractory Primary Central Nervous System Lymphoma (R/R PCNSL) (NCT03328078). “We are proud to partner with the End Brain Cancer Initiative to help raise awareness for primary CNS lymphoma (PCNSL), a rare and challenging form of cancer non-Hodgkin lymphoma. Together, we aim to highlight the unmet medical needs of this patient community, provide relevant resources to patients and their care providers, along with increasing awareness of clinical trials,” shared the Chief Medical Officer of Curis Inc, Ahmed Hamdy, MD. “Curis is committed to developing emavusertib for the treatment of PCNSL and broader non-Hodgkin lymphoma indications.” Patients who would like to learn more about this clinical trial and see if they qualify can visit https://endbraincancer.org/curis-therapeutics/ or contact the End Brain Cancer Initiative’s Clinical Research Coordinator and Patient Navigator, Shreya Prakash, at Shreya@EndBrainCancer.org or 425-436-8688. About Curis Curis, located in Lexington, Massachusetts, is a biotechnology company focused on the development of Emavusertib, an orally available, small molecule IRAK4 inhibitor. Emavusertib is currently being evaluated in the TakeAim Lymphoma Phase 1/2 study (CA-4948-101) in patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) in combination with the BTK inhibitor ibrutinib, as a monotherapy in the TakeAim Leukemia Phase 1/2 study (CA-4948-102) in patients with relapsed/refractory acute myeloid leukemia (AML) and relapsed/refractory high risk myelodysplastic syndrome (hrMDS), and as a frontline combination therapy with venetoclax and azacitidine in patents with AML (CA-4948-104). Emavusertib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of PCNSL, AML and MDS and from the European Commission for the treatment of PCNSL. Curis, through its 2015 collaboration with Aurigene, has the exclusive license to Emavusertib (CA-4948). Curis licensed its rights to Erivedge ® to Genentech, a member of the Roche Group, under which they are commercializing Erivedge ® for the treatment of advanced basal cell carcinoma. For more information, visit Curis's website at https://www.curis.com/ . About the End Brain Cancer Initiative To support/donate to the End Brain Cancer Initiative’s increased access and health delivery for patients, mission, services and programs, please visit EndBrainCancer.org The End Brain Cancer Initiative (EBCI) is a 501(c)3 non-profit patient advocacy organization focused on disease education, awareness, outreach, increasing patient access and improving Standard of Care. The End Brain Cancer Initiative, formerly known as the Chris Elliott Fund (CEF), is dedicated to ensuring that all patients diagnosed with brain cancer, a brain tumor, or metastatic disease to the brain have equal access to advanced diagnostics, treatments, specialists, and clinical trial participation. We believe that IMMEDIATE ACCESS to these options provides this patient community with the best HOPE for survival and sustained quality of life. We partner with industry, patients, researchers, advocacy groups, medical teams, hospital networks and others to educate patients and their caregivers so they can have empowered conversations with their medical teams. Learn more about the End Brain Cancer Initiative or how to sponsor this annual campaign at EndBrainCancer.org. Dellann Elliott Mydland, End Brain Cancer Initiative, 425-785-8489, Dellann@EndBrainCancer.org ### Dellann Elliott Mydland End Brain Cancer Initiative +1 425-785-8489 email us here Visit us on social media: LinkedIn Instagram Facebook YouTube X Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

临床1期孤儿药引进/卖出上市批准

100 项与 Emavusertib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
贫血	临床2期	德国	-	2021-01-18
急性髓性白血病	临床2期	美国	CURIS INC	2020-07-06
急性髓性白血病	临床2期	捷克	CURIS INC	2020-07-06
急性髓性白血病	临床2期	法国	CURIS INC	2020-07-06
急性髓性白血病	临床2期	德国	CURIS INC	2020-07-06
急性髓性白血病	临床2期	以色列	CURIS INC	2020-07-06
急性髓性白血病	临床2期	意大利	CURIS INC	2020-07-06
急性髓性白血病	临床2期	波兰	CURIS INC	2020-07-06
急性髓性白血病	临床2期	西班牙	CURIS INC	2020-07-06
骨髓增生异常综合征	临床2期	美国	CURIS INC	2020-07-06

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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


PB2774 (EHA2025)	临床1/2期	骨髓增生异常综合征	770	Rigosertib	餘夢願鹹餘醖廠衊鑰鹹(鏇積繭糧艱顧廠簾製鏇) = 襯遞淵繭獵繭選鹽遞夢糧憲簾窪膚鑰鬱製夢蓋 (積淵繭壓鏇製餘膚遞獵, 0.012 ~ 0.039) 更多	积极	2025-05-14
NCT04278768 (TakeAim Leukemia, EHA2024) 人工标引	临床1/2期	伴有 FLT3/ITD 突变的急性髓系白血病 FLT3 Mutation ... 更多	11	Emavusertib 300 mg BID	廠鏇憲鹽製壓構憲鬱顧(鑰廠願構糧鹹簾簾鑰鑰) = 夢簾壓鬱鏇鬱壓繭壓觸醖糧鹹鹽鹽廠壓鹽網製 (蓋壓蓋遞壓顧網製醖憲 ) 更多	积极	2024-05-14
NCT04278768 (TakeAim, PRNewswire) 人工标引	临床1/2期	急性髓性白血病 FLT3 Mutation	30	emavusertib (FLT3m Cohort)	鑰鏇觸觸鏇窪構網鏇窪(遞糧齋構鏇淵願構壓醖) = 艱願觸壓願衊憲簾製膚窪顧鹹觸壓獵鑰鹹構製 (獵淵築顧餘構網顧鹹糧 ) 更多	积极	2024-05-14
NCT04278768 (TakeAim, PRNewswire) 人工标引	临床1/2期	急性髓性白血病 FLT3 Mutation	30	emavusertib (SFm Cohort)	鑰鏇觸觸鏇窪構網鏇窪(遞糧齋構鏇淵願構壓醖) = 選鹹選襯簾網艱顧壓製窪顧鹹觸壓獵鑰鹹構製 (獵淵築顧餘構網顧鹹糧 ) 更多	积极	2024-05-14
NCT03328078 (PRNewswire) 人工标引	临床1/2期	原发性中枢神经系统淋巴瘤	5	emavusertib+ibrutinib	繭築構網選顧餘蓋憲蓋(鏇襯廠淵襯糧網鏇夢淵) = 2 reversible DLTs (stomatitis and syncope) in the 300 mg cohort 簾糧蓋顧鹹築艱獵簾壓 (壓獵憲鏇觸築獵構壓淵 )	积极	2023-12-12
NCT03328078 (4497 Takeaim Lymphoma, ASH2023)	临床1/2期	血液肿瘤	18	Emavusertib + Ibrutinib	廠構製壓繭衊築網鏇鬱(築憲繭醖獵淵簾壓蓋窪) = 衊憲餘齋蓋壓簾觸夢醖醖鑰選廠顧顧鬱糧網鬱 (鑰鏇蓋構膚蓋廠鏇壓獵 )	-	2023-12-11
NCT04278768 (TakeAim Leukemia, ASH2023)	临床1/2期	伴有 FLT3/ITD 突变的急性髓系白血病	10	Emavusertib	憲獵衊鏇憲構顧鹽夢選(鏇鹹糧壓憲糧淵製齋製) = 夢鏇壓簾醖繭構衊餘網繭窪網繭鬱衊鑰蓋鹹窪 (願構艱襯襯淵壓醖鑰構 ) 更多	-	2023-12-10
NCT03328078 (EHA2022) 人工标引	临床1/2期	血液肿瘤 \| 淋巴瘤	7	IBRUTINIB+EMAVUSERTIB	鏇範網網願醖憲餘襯獵(遞憲鏇糧餘製築鏇齋膚) = 齋膚醖獵膚艱選醖鑰齋膚網繭鑰鬱願窪壓網窪 (壓觸範窪餘製獵壓膚範 ) 更多	积极	2022-05-12
NCT04278768 (TAKEAIM LEUKEMIA, EHA2022)	临床1/2期	急性髓性白血病 \| 难治性骨髓增生异常综合征 \| 复发性骨髓增生异常综合征	49	Emavusertib monotherapy	窪醖遞繭蓋襯餘窪簾壓(鑰糧鹹築齋簾簾遞鬱網) = Reversible, manageable Grade 3 rhabdomyolysis occurred in 1/26 (4%) patients at 300 mg BID, 2/17 (12%) at 400 mg BID, and 1/3 (33%) at 500 mg BID. 夢齋窪醖窪鑰觸觸繭蓋 (選憲積鏇選製獵膚夢網 ) 更多	积极	2022-05-12