Advanced pancreatic cancer patients receiving treatment of adaptive stereotactic body radiotherapy (SBRT) with concurrent and adjuvant defactinib plus avutometinib will have increased progression-free survival (PFS) compared to historical PFS rates for patients receiving adaptive SBRT alone.

开始日期2025-11-30

申办/合作机构

Washington University School of Medicine

[+2]

NCT06104488

/ Recruiting临床1期IIT

A Multi-Center Phase I Dose Escalation Study of Avutometinib, a RAF/MEK Clamp, in Pediatric Patients With Refractory or Recurrent Solid Tumors Harboring Activating MAPK Pathway Alterations

The purpose of this study is to find out whether avutometinib is a safe treatment for advanced or recurrent solid tumor cancers in children and young adults. Researchers will look for the highest dose of avutometinib that is safe and cause few or mild side effects.

开始日期2023-10-20

申办/合作机构

Memorial Sloan Kettering Cancer Center

NCT05669482

/ Recruiting临床1/2期

A Phase 1b/2a Study of Gemcitabine and Nab-paclitaxel in Combination With Avutometinib (VS-6766) and Defactinib in Patients With Previously Untreated Metastatic Adenocarcinoma of the Pancreas

This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with Pancreatic Ductal Adenocarcinoma (PDAC) who have been previously untreated.

开始日期2023-03-22

申办/合作机构

Verastem, Inc.

100 项与 Avutometinib 相关的临床结果

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100 项与 Avutometinib 相关的转化医学

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100 项与 Avutometinib 相关的专利（医药）

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项与 Avutometinib 相关的文献（医药）

2025-12-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Anti-tumor efficacy of RAF/MEK inhibitor VS6766 in KRAS-mutated colorectal cancer cells

Article

作者: Tan, Biqin ; Ma, Junjie ; Yan, Youyou ; Dong, Rong ; Zhu, Haixin ; Yan, Gezi ; Lin, Nengming ; Zhang, Bo ; Zhu, Lulin

PURPOSE:

Colorectal cancer (CRC) ranks third among most prevalent cancers worldwide. KRAS is the most frequently (30-40%) mutated oncogene in CRC, which has been defined as an "undruggable" therapeutic target over the past four decades.

METHODS:

In this study, we applied four HT-29 cell lines, namely HT-29-wild-type (HT-29-WT), point-mutated HT-29-KRAS^G12V, HT-29-KRAS^G12C and HT-29-KRAS^G12D, in order to detect the efficiency of RAF-MEK inhibitor VS6766, the BRAF^V600E inhibitor PLX4720 was selected as the control. The analyses of in vitro cytotoxicity, cell cycle and apoptosis of HT-29 cell lines after VS6766 alone or combined with 5-Fluorouracil (5-FU)/MK2206 treatment were carried out by Cell Counting Kit-8 (CCK-8), colony formation, and flow cytometry assay, respectively. The expression changes of proteins were confirmed by western blot.

RESULTS:

Treatment with VS6766 inhibited the proliferation of all four HT29 cells, while PLX4720 had a modest inhibitory effect. VS6766 induced G1-phase arrest as well as cell apoptosis, accompanied by the downregulation of p-ERK and p-MEK. Moreover, VS6766 and 5-FU synergistically suppressed HT-29 cells' growth. Meanwhile, p-AKT was upregulated after VS6766 treatment. The AKT inhibitor MK2206 and VS6766 showed synergistic effect in all four cell lines.

CONCLUSION:

Taken together, this study provides the first experimental evidence to demonstrate that all G12 mutation cell lines are sensitive to VS6766 applied either alone or combined with 5-FU or AKT inhibitor.

2025-07-17·GYNECOLOGIC ONCOLOGY

The RAS-MEK-ERK pathway in low-grade serous ovarian cancer.

Review

作者: Lee, Elizabeth K ; Shapiro, Geoffrey I ; Stover, Elizabeth H ; Matulonis, Ursula A ; Liu, Joyce F ; Brugge, Joan S

Low-grade serous ovarian cancer (LGSC) is an uncommon subtype of epithelial ovarian cancer, often arising in association with serous borderline tumors (SBT). Compared to high-grade serous ovarian cancers, LGSCs often occur in younger patients and are relatively insensitive to platinum-based chemotherapy, though some patients with LGSC can benefit from hormonal therapies. Genomic studies have demonstrated that SBT and LGSC frequently harbor mutations in members of the RAS-MEK-ERK pathway, which can be targeted therapeutically. LGSC harbor mutations in KRAS (up to 54 %, primarily non-G12C mutations), NRAS, and BRAF. Treatment of recurrent LGSC with the MEK inhibitor trametinib demonstrated improved clinical outcomes relative to other treatment options (chemotherapy, hormonal therapy) in a phase 3 trial. Other MEK inhibitors have also shown efficacy in LGSC, with some studies demonstrating higher response rates in patients whose tumors harbor KRAS mutations. However, some trials of MEK inhibitors showed more limited benefit (e.g. binimetinib), and RAS pathway mutations do not always correlate with increased efficacy, highlighting the need for further clinical and translational research in RAS-MEK-ERK pathway targeted therapeutics. Current clinical trials are evaluating MEK inhibitor combinations such as MEK inhibitors plus inhibitors of poly (ADP-ribose) polymerase (PARP), AKT, PI3K, CDK4/6, or BCL2/BCL-XL. Novel approaches to targeting the RAS-MEK-ERK pathway include the RAF/MEK clamp avutometinib, which has been evaluated in combination with the FAK inhibitor defactinib, and this combination received United States Food and Drug Administration (FDA) accelerated approval in 2025. Multiple newly developed inhibitors of KRAS, including KRAS G12C or G12D inhibitors, as well as pan-RAS inhibitors, including RAS (ON) inhibitors such as RMC-6236, are being evaluated in solid tumors. These emerging strategies for inhibiting RAS-MEK-ERK pathway activity may offer new treatment options for patients with LGSC.

2025-07-01·CHEMISTRY & BIODIVERSITY

Integrated Computational and Experimental Insights Into MEK1/2 Inhibitors: Structural Validation, Docking, ADMET, Molecular Dynamics, and Anticancer Evaluation

Article

作者: Teli, Ghanshyam ; Matada, Gurubasavaraja Swamy Purawarga ; Pal, Rohit

ABSTRACT:

This study explores the therapeutic potential of novel MEK1/2 inhibitors targeting the MAPK pathway, emphasizing their critical role in cancer progression. An integrated computational approach, including molecular docking, pharmacophore modeling, molecular dynamics simulations, and DFT analysis, was employed to evaluate the binding affinity, stability, and pharmacological properties of FDA‐approved and experimental compounds. Structural validation of MEK1 (PDB ID: 1S9J) and MEK2 (PDB ID: 1S9I) revealed z‐scores of −6.89 and −7.13, respectively, with 90.6% and 86.7% of residues in the most favored regions, confirming the reliability of the protein models. Docking studies identified RO5126766 as a lead compound, exhibiting binding energies of −10.1 kcal/mol with MEK1 and −9.5 kcal/mol with MEK2. Molecular dynamics simulations further demonstrated the stability of the RO5126766–MEK1 and RO5126766–MEK2 complexes, with RMSD values ranging from 0.95 to 4.22 Å. The in vitro anticancer assays highlighted the exceptional potency of RO5126766, with IC50 values of 12.87 ± 98.36 nM against MCF‐7 (hormone receptor‐positive breast cancer), 15.08 ± 94.36 nM against MDA‐MB‐231 (triple‐negative breast cancer), and 60.89 ± 70.58 nM against A549 (lung cancer). ADMET analysis confirmed high gastrointestinal absorption, favorable drug‐likeness, and lack of blood‐brain barrier permeability. In addition, DFT studies indicated an optimal HOMO–LUMO energy gap (0.15816 eV), chemical hardness (0.16189 eV), and strong molecular interactions corroborated by MEP analysis. Collectively, these findings establish RO5126766 as a potent and selective MEK1/2 inhibitor, demonstrating significant potential as a targeted therapeutic agent for aggressive and treatment‐resistant cancers.

116

项与 Avutometinib 相关的新闻（医药）

2025-08-14

·PipelineReview

Verastem Oncology Announces Late-Breaking Abstract from Partner GenFleet Therapeutics’ Study in China of GFH375 (VS-7375) in Advanced Non-Small Cell Lung Cancer at IASLC 2025 World Conference on Lung Cancer

GFH375 demonstrated an overall response rate (ORR) of 68.8% in non-small cell lung cancer (NSCLC) at the recommended Phase 2 dose of 600 mg QD GFH375 demonstrated an ORR of 57.7% in efficacy evaluable patients with NSCLC across all dose levels Mini oral presentation on Sunday, September 7, 2025 from 12:00 to 1:15 pm (CEST) BOSTON, MA, USA I August 13, 2025 I Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK-pathway-driven cancers, today announced positive, updated safety and efficacy data and late-breaking presentation details of partner GenFleet Therapeutics’ Phase 1/2 study in China of GFH375, an oral KRAS G12D (ON/OFF) inhibitor, known as VS-7375 outside of China, in advanced non-small cell lung cancer patients with a KRAS G12D mutation. The data will be presented in a mini oral presentation at the IASLC 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer from September 6-9, in Barcelona, Spain. “These data at WCLC build on the encouraging data presented at ASCO earlier this year, where GenFleet initially reported an ORR of 42% in 12 patients with advanced non-small cell lung cancer harboring a KRAS G12D mutation,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “The significant increase in patients with advanced lung cancer demonstrating a response, 68.8% ORR at the recommended Phase 2 dose, and 57.7% ORR across all dose levels, is impressive and continues to support the development and potential of VS-7375 in advanced lung cancer and across other advanced KRAS G12D solid tumors.” The late-breaking abstract was issued today by the WCLC. GenFleet reported cumulative safety data across the entire study population and preliminary efficacy data specific to patients with advanced NSCLC from the Phase 1/2 study in China. As of the data cutoff of July 15, 2025, the median follow-up time was 4.5 (range: 1.8-12.2) months. Tumor response was observed across the dose range tested. The study population includes 142 patients, including 28 with advanced NSCLC, 85 with advanced pancreatic ductal adenocarcinoma (PDAC) and 29 with other solid tumors. Amongst the patients with NSCLC, all had metastatic disease at baseline, 64.3% had received at least two prior lines of systemic therapies, and 96.4% had received an anti-PD1/PD-L1 therapy. At the recommended Phase 2 dose of 600 mg once daily (QD), the ORR was 68.8% (11/16) (both confirmed and unconfirmed) and the disease control rate (DCR) was 93.8% (15/16). Among the 26 evaluable patients with NSCLC treated across all dose levels, the ORR was 57.7% (15/26) (both confirmed and unconfirmed) and the DCR was 88.5% (23/26). Across all cancer types and dose levels evaluated, the most common treatment-related adverse events (TRAEs) occurring in at least 20% of patients were diarrhea, vomiting, nausea, anemia, decreased appetite, neutrophil count decreased, white blood cell count decreased, aspartate aminotransferase increased, asthenia, hypoalbuminemia, and alanine aminotransferase increased, predominately Grade 1 or 2 in severity. TRAEs and severe adverse events (SAEs), greater than Grade 3, occurred in 27.5% (39/142) and 7.7% (11/142) of patients, respectively. Of the 142 patients in the safety population, 11 patients had dose reduction, and six discontinued due to TRAEs. No TRAE-related deaths were reported. WCLC Details About KRAS G12D KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. The KRAS G12D mutation occurs most commonly in pancreatic (37%), colorectal (12.5%), endometrial (8%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer. About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor VS-7375 is a potential best-in-class, potent, and selective oral KRAS G12D dual ON/OFF inhibitor. VS-7375 is the lead program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. Verastem announced in April 2025 that the U.S. Investigational New Drug (IND) application for VS-7375 was cleared and initiated a Phase 1/2a clinical trial in June 2025. GenFleet’s IND for VS-7375 (known as GFH375 in China) was approved in China in June 2024, and the first patient was dosed in a Phase 1/2 study in July 2024. About the GenFleet Therapeutics Collaboration The collaboration with GenFleet Therapeutics aims to advance three oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase 1 trial. Verastem selected VS-7375 (also known as GFH375), an oral KRAS G12D (ON/OFF) inhibitor, as its lead program in December 2023 and the license for VS-7375 that was exercised in January 2025 is the first one from this collaboration. These licenses give Verastem development and commercialization rights outside the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan. About Verastem Oncology Verastem Oncology (Nasdaq: VSTM) is a biopharmaceutical company committed to developing and commercializing new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Verastem markets AVMAPKI™ FAKZYNJA™ CO-PACK in the U.S. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition, and KRAS G12D inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn . SOURCE: Verastem Oncology

临床结果临床申请临床1期临床2期引进/卖出

2025-08-13

·药明康德

致敬时代 | 从50%死亡率到生存率接近翻倍：卵巢癌治疗的突破之路

编者按：2025年，药明康德迎来创立25周年的重要里程碑。值此契机，我们向所有与我们共同书写产业变革篇章的科学家、医药人和投资者致以衷心感谢与诚挚敬意，也特别推出“致敬时代”系列，回顾全球同仁如何借助科学与合作的力量，不断拓展治疗边界、改善患者命运。四分之一个世纪的坚守，只为加速每一款新药的诞生。下一个25年，我们将继续心怀感恩与敬畏，依托独特的CRDMO模式，与全球伙伴携手同行，共赴健康未来。在全球女性癌症谱系中，卵巢癌一直以“难治”著称。“神刊”CA：A Cancer Journal for Clinicians杂志发布的2025年癌症统计报告显示，卵巢癌的致死率在女性癌症中高居第六位。导致卵巢癌如此难治的原因之一是其早期症状十分隐匿，约70%的患者在确诊时已处于晚期。再加上复发率高、预后较差等因素，卵巢癌也成为了主要的“妇女杀手”之一。近十余年来，随着靶向治疗时代的开启和新型分子疗法的不断涌现，卵巢癌的治疗格局迎来了新的转机。当我们回望整个卵巢癌治疗的发展史，不仅能看到各类治疗手段的迭代演进，更能感受到全球各界的协同创新，共同推动着卵巢癌治疗领域的每一次重大突破。图片来源：123RF 从开创性手术到现代治疗在人类对抗卵巢癌的医学探索史上，1809年是一个重要的开端。那年圣诞节，美国医生以法莲·麦克道尔（Ephraim McDowell）在没有麻醉和消毒的条件下，成功为一名46岁女性切除了重达10公斤的卵巢肿瘤。这也是首个被详细记录的卵巢肿瘤切除手术。这位被后世尊为“卵巢手术之父”的医生可能想象不到，他这次冒险的手术开创了一个全新的医学领域。受限于技术条件，在那个年代做手术的危险性可能比癌症本身还致命。直到大半个世纪后的1882年，英国外科医生托马斯·斯宾塞·威尔斯（Thomas Spencer Wells）改良了卵巢手术技术，并将无菌技术和麻醉引入手术，才将当时手术的死亡率从惊人的50%降至11%。到了20世纪初，英国著名的妇科外科医生维克多·邦尼（Victor Bonney）又进一步推动了妇科手术的进步——他发明的“邦尼蓝”消毒液改善了术中消毒流程，大幅降低了术后感染率。在一代代医学工作者的不懈探索与临床实践积累下，手术治疗就这么一步步地成为了卵巢癌的主要治疗手段。图片来源：123RF 20世纪中叶，随着放射治疗的引入，卵巢癌治疗进入了新的阶段。那时，全腹放疗（WAR）被用于治疗卵巢癌的腹腔转移。然而，该疗法始终面临着剂量选择的两难困境：若采用低剂量放疗以保护腹腔内的正常器官，则难以达到理想的肿瘤控制效果；而若提高剂量以确保疗效，又往往会产生严重的急性毒性反应使患者无法耐受。更棘手的是，高达20%的患者会出现放射性肺炎，15%会遭受不可逆的肝损伤，这些严重的长期毒性让医生们不得不寻找更安全的替代方案。转机出现在20世纪70年代。随着能破坏癌细胞DNA结构的铂类化疗药物的问世，卵巢癌治疗终于迎来了突破。1978年，首款用于治疗卵巢癌的铂类抗肿瘤药物顺铂获得了FDA批准，从这种治疗中受益的患者人数达数百万。随后问世的第二代铂类药物卡铂则能够在保持疗效的同时大幅降低不良反应。进入80年代后，紫杉烷类药物的发现进一步为卵巢癌患者提供了更多的治疗选择。这类源自天然植物的抗癌药物通过独特的微管稳定机制发挥作用，还能与铂类药物形成互补。基于良好的临床试验结果，肿瘤切除术后辅以铂类（顺铂/卡铂）联合紫杉烷类（紫杉醇/多西他赛）化疗成为了卵巢癌的新一代标准治疗方案。从“无差别杀伤”到“精准打击” 自基于铂类药物的组合化疗成为标准治疗后，晚期卵巢癌患者的5年生存率提高到了约25%，但仍然不是一个能够令人满意的数字。约80%的患者在接受一线治疗后有望获得完全缓解，然而残酷的是，60%-80%患者会在18个月内因化疗耐药复发，即便二线治疗有效，85%患者仍会在两年内再次出现疾病进展。对于这些出现完全缓解或部分缓解的患者来说，如何在化疗后继续保持“缓解状态”有着巨大的未竟医疗需求。 21世纪初，靶向治疗时代拉开了帷幕，也为卵巢癌的治疗带来了突破。这一时期的医学发展开始从“无差别杀伤”的传统化疗模式，转向针对肿瘤特定分子特征的“精准打击”策略。图片来源：123RF 2011年，欧洲率先批准了抗血管生成药物Avastin（bevacizumab，贝伐珠单抗）与铂-紫杉烷类化疗的联合方案，用于晚期卵巢癌的一线治疗及维持治疗。该药物通过抑制肿瘤血管生成来“饿死”癌细胞，与化疗联用可显著延长无进展生存期。三年后，美国FDA也批准了该药在铂类耐药复发性卵巢癌二线治疗中的应用。作为一类在卵巢癌领域取得突破的生物制品，贝伐珠单抗虽然能暂时延缓疾病进展，却难以显著延长患者的总生存时间，加上该药有可能引发高血压、血栓甚至胃肠道穿孔等不良反应的风险，医学界寄希望于找到更加安全有效的新疗法。 “合成致死”，针对卵巢癌的常见突变 2014年，随着首款PARP抑制剂的问世，卵巢癌的治疗格局发生了革命性的变化。这一突破可追溯至1922年哥伦比亚大学Calvin Bridges博士发现的“合成致死”现象：当两个特定基因同时发生突变时会导致生物体死亡，而这两个基因单独突变却不会产生致命影响。半个世纪后，一些科学家基于这个现象提出，合成致死可能为抗癌药物开发提供新的策略。这一想法终于在2005年得到了验证——两支研究团队在《自然》杂志上发表里程碑成果，首次证实了PARP抑制剂与BRCA突变存在“合成致死”效应。BRCA基因突变会破坏癌细胞修复DNA双链断裂的能力，而PARP抑制剂则能阻断另一条修复单链断裂的通路。当这两种修复机制同时被抑制时，癌细胞就会因无法修复DNA损伤而死亡，这就是“合成致死”效应的具体体现。 ▲合成致死作用机制在抗癌药物开发中的应用（图片来源：参考资料[6]）这一突破性发现也为卵巢癌治疗开辟了新方向。由于约15%的卵巢癌患者携带BRCA基因突变，研究人员意识到，PARP抑制剂也有可能成为卵巢癌患者的理想靶向治疗选择。经过近十年的临床验证，2014年12月，首款PARP抑制剂Lynparza（olaparib，奥拉帕利）获得FDA批准上市，用于治疗携带BRCA种系突变的晚期卵巢癌患者。奥拉帕利的成功催生了更多PARP抑制剂的研发。2016年，Zejula（niraparib，尼拉帕利）的临床试验数据进一步扩展了受益人群，显示其对同源重组修复缺陷（HRD）阳性的非BRCA突变患者同样有效。截至目前，全球上市的PARP抑制剂已达7款，其中6款都获批用于治疗卵巢癌，除了奥拉帕利和尼拉帕利，还有派舒宁（塞纳帕利）、百汇泽（帕米帕利）、艾瑞颐（氟唑帕利）和Rubraca（rucaparib）。这些药物通过精准打击癌细胞的DNA修复缺陷，显著延长了患者的无进展生存期。随着在一线治疗中引入PARP抑制剂维持治疗，卵巢癌患者的生存率进一步提高。在一项临床试验中，晚期高风险患者的5年生存率已超过40%。这一突破性进展源于多重因素的协同作用：手术技术的革新使肿瘤减灭更加彻底，化疗方案的优化提升了初始治疗效果，再加上PARP抑制剂维持治疗的精准应用和靶向药物的合理选择延迟了肿瘤复发的进程。百花齐放：从靶向药到免疫疗法在PARP抑制剂取得显著成效的同时，针对其他靶点的创新疗法也相继问世，进一步丰富了卵巢癌的治疗选择。以叶酸受体α（FRα）靶点为例，尽管FRα在35-40%的卵巢癌中高表达，但长期以来缺乏有效靶向药物。2022年11月，全球首个靶向FRα的抗体偶联药物（ADC）Elahere（mirvetuximab soravtansine）获得FDA加速批准。这款ADC通过将抗FRα单抗与细胞毒性分子DM4偶联，实现了对铂类耐药卵巢癌的精准打击。新闻稿指出，该疗法是首个在铂类耐药卵巢癌患者上显示带来总生存期（OS）改善的疗法。在关键的3期临床试验中，Elahere组患者的中位OS为16.46个月，较研究者选择（IC）化疗组的12.75个月延长了近4个月。在对化疗的应答率较低的卵巢癌亚型治疗方面，2025年5月，FDA加速批准RAF/MEK抑制剂avutometinib联合FAK抑制剂defactinib方案（Avmapki Fakzynja Co-Pack）用于KRAS突变型复发性低级别浆液性卵巢癌（LGSOC）。Avutometinib能够同时抑制RAF和MEK，克服了传统MEK抑制剂的代偿性激活问题。在Avastin的基础上，新一代重组人源化抗血管内皮生长因子（VEGF）抗体苏维西塔单抗于今年7月获中国国家药品监督管理局（NMPA）批准，可与紫杉醇、多柔比星脂质体或拓扑替康联用治疗铂耐药后接受过不超过1种系统治疗的成人复发性卵巢癌、输卵管癌或原发性腹膜癌的治疗。在一项3期临床试验中，与对照组相比，苏维西塔单抗组也呈现出OS获益趋势（16.07个月对比14.88个月）。值得一提的是，苏维西塔单抗的临床应用不受前线VEGF通路治疗和PARP抑制剂靶向治疗的限制，与化疗联用也不受化疗药物种类限制。除以上靶点外，有极少数卵巢癌患者（约1-2%）存在着NTRK基因融合突变，这种突变会驱动异常细胞生长和癌症进展。Vitrakvi（larotrectinib，拉罗替尼）和Rozlytrek（entrectinib，恩曲替尼）可阻断突变NTRK基因产生异常蛋白质。这些药物能够用于治疗那些存在NTRK基因突变、且经过其他治疗方案后病情仍然进展的晚期卵巢癌患者。在靶向治疗取得突破的同时，免疫治疗也为卵巢癌患者带来了新的希望。人体免疫系统通过“检查点”机制来防止攻击正常细胞，而癌细胞常会利用这一机制逃避免疫监视。以PD-1/PD-L1抑制剂为代表的免疫检查点抑制剂，通过阻断这一逃逸通路，能够重新激活T细胞对癌细胞的杀伤作用。 PD-1抑制剂Keytruda（pembrolizumab，帕博利珠单抗）、Jemperli（dostarlimab）和百泽安（替雷利珠单抗）均已获得监管批准，用于治疗不可切除或转移性微卫星高度不稳定型（MSI-H）或错配修复基因缺陷型（dMMR）的晚期实体瘤患者，其中也包括卵巢癌患者。这些靶向治疗和免疫疗法的不断涌现，使得卵巢癌治疗从传统的“一刀切”模式逐步迈向精准化、个体化的新时代。随着对卵巢癌分子机制认识的深入和更多创新药物的开发，临床医生能够根据患者的分子特征选择最适合的治疗方案，为不同亚型的卵巢癌患者带来更有针对性的治疗选择。一体化平台赋能卵巢癌新药开发从两个世纪前开创性的卵巢切除术，到如今的精准治疗，人类对抗卵巢癌的征程已走过漫长而艰辛的道路。一方面看，卵巢癌的治疗手段不断革新——从手术加化疗，到靶向治疗，再到更多新兴疗法，给患者带来了新的希望。但另一方面，晚期卵巢癌患者的五年生存率仍未突破50%的大关。这一数字时刻提醒我们：与这个“沉默杀手”的较量依然任重道远。根据公开资料，目前有数百种卵巢癌疗法已进入临床开发阶段，针对百余种不同的靶点。长期以来，药明康德都在支持全球合作伙伴从药物研究（R）、开发（D）到商业化生产（M）各个阶段的需求，通过独特的一体化、端到端CRDMO模式，助力突破性疗法加速研发进程、早日惠及患者。我们很高兴能赋能卵巢癌新药的开发，也将继续与全球合作伙伴携手同行，共同推动卵巢癌治疗的突破，让更多患者迎来曙光！参考资料： [1] Tavares V, Marques IS, Melo IG, Assis J, Pereira D, Medeiros R. Paradigm Shift: A Comprehensive Review of Ovarian Cancer Management in an Era of Advancements. Int J Mol Sci. 2024 Feb 3;25(3):1845. doi: 10.3390/ijms25031845. PMID: 38339123; PMCID: PMC10856127. [2] Lumish MA, Kohn EC, Tew WP. Top advances of the year: Ovarian cancer. Cancer. 2024 Mar 15;130(6):837-845. doi: 10.1002/cncr.35135. Epub 2023 Dec 15. PMID: 38100616. [3] Barber HR. New frontiers in ovarian cancer diagnosis and management. Yale J Biol Med. 1991 Mar-Apr;64(2):127-41. PMID: 1721478; PMCID: PMC2589481. [4] Ozols RF. Ovarian cancer. Semin Surg Oncol. 1990;6(6):328-38. doi: 10.1002/ssu.2980060607. PMID: 2263808. [5] European contributions to the diagnosis and treatment of ovarian cancer: a historical and modern perspective. Retrieved August 7, 2025, from https://www.oncopedia.wiki/contributions/european-contributions-to-the-diagnosis-and-treatment-of-ovarian-cancer-a-historical-and-modern-perspective [6] Ngoi et al., (2024). Synthetic lethal strategies for the development of cancer therapeutics. Nature Reviews Clinical Oncology, https://doi.org/10.1038/s41571-024-00966-z 免责声明：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。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

放射疗法

2025-08-13

·药精通Bio

FDA 2025 上半年获批新药

OTC2025论坛深度聚焦类器官与疾病建模、新药发现/研发、3D细胞培养、类器官培养及质控。OTC2026合作热线：王晨180 1628 8769 FDA 药物评价与研究中心（CDER）在 2025 年上半年批准了 16 种新药。这些新药涵盖肿瘤学、疼痛、罕见病、免疫学和传染病预防。 💉 Datopotamab deruxtecan （Datroway） Trop-2 定向 mAb + 拓扑异构酶抑制剂 ADC，用于转移性 HR 阳性、HER2 阴性乳腺癌。 💉 三维硫烷（Grafapex） DNA 烷化剂 + 氟达拉滨作为 AML 或 MDS 中同种异体造血干细胞移植的制备方案。 💊 Suzetrigine （Journavx）口服 Nav1.8 抑制剂，非阿片类镇痛药，用于中度至重度急性疼痛。 💊 Mirdametinib （Gomekli）用于 1 型神经纤维瘤病的口服双 MEK2/1 抑制剂。 💊 Vimseltinib （Romvimza）口服 CSF1R 激酶抑制剂，用于有症状的腱滑突巨细胞瘤。 💊 Gepotidacin （Blujepa）用于急性膀胱炎和淋病的细菌 DNA 旋转酶/拓扑异构酶 IV 抑制剂，包括 MDR 菌株。 💉 Fitusiran （Qfitlia）用于预防血友病 A 或 B 的抗凝血酶 siRNA（GalNAc 偶联），有或没有抑制剂。 💊 Atrasentan （Vanrafia）内皮素 A 受体拮抗剂，可减少原发性 IgA 肾病中的蛋白尿。 💉 Penpulimab PD-1 mAb 用于非角化性鼻咽癌。 💉 Nipocalimab （Imaavy）用于全身性重症肌无力的 FcRn 结合单克隆抗体。 💊 Avutometinib/defactinib （Avmapki Fakzynja Co-Pack）用于 KRAS 突变的复发性低级别浆液性卵巢癌。 💉 Telisotuzumab vedotin （Emrelis） c-Met 定向 ADC，具有微管破坏有效载荷，用于 NSCLC。 👁️ Acoltremon（色蛋白荠）用于干眼症的 TRPM8 钙通道激活剂。 💉 Clesrovimab （Enflonsia）用于婴儿被动免疫的 RSV 融合蛋白定向单克隆抗体。 💊 Taletrectinib （Ibtrozi） ROS1 / pan-NTRK 抑制剂，用于 ROS1 阳性 NSCLC。 💉 Garadacimab （Andembry）用于预防遗传性血管性水肿的因子 XII 定向单克隆抗体。 END 免责声明：本文仅作知识交流与分享及科普目的，不涉及商业宣传，不作为相关医疗指导或用药建议。文章如有侵权请联系删除。 OTC2025论坛深度聚焦类器官与疾病建模、新药发现/研发、3D细胞培养、类器官培养及质控。OTC2026合作热线：王晨180 1628 8769

抗体药物偶联物siRNA优先审批引进/卖出

100 项与 Avutometinib 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
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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
晚期胰腺腺癌	临床2期	美国	Verastem, Inc.	2025-11-30
胰腺腺癌	临床2期	美国	Verastem, Inc.	2025-11-30
HR阳性乳腺癌	临床2期	美国	Eli Lilly & Co.	2023-02-23
HR阳性乳腺癌	临床2期	美国	Verastem, Inc.	2023-02-23
HR阳性/HER2阴性乳腺癌	临床2期	美国	Verastem, Inc.	2023-02-23
HR阳性/HER2阴性乳腺癌	临床2期	美国	Eli Lilly & Co.	2023-02-23
转移性胰腺腺癌	临床2期	美国	Verastem, Inc.	2023-01-15
大肠腺癌	临床2期	美国	Verastem, Inc.	2022-08-22
晚期结直肠腺癌	临床2期	美国	Verastem, Inc.	2022-08-22
KRAS 突变结直肠癌	临床2期	美国	Verastem, Inc.	2022-08-22

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临床结果

适应症

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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


NCT05669482 (RAMP 205, ASCO2025)	临床1/2期	转移性胰腺导管腺癌一线 activating KRAS mutations	54	Avutometinib/Defactinib + Gemcitabine/nab-paclitaxel	鬱衊壓繭膚膚願獵壓鏇(製觸窪餘鏇淵觸遞選鹹) = 41% 鬱膚築醖鹹鹹壓遞選鑰 (餘獵繭鹽繭製齋獵構鏇 ) 更多	积极	2025-05-30
phase 1 trial (AACR2025)	临床1期	转移性乳腺癌 CDK4/6 inhibitor (CDK4/6i)	16	Avutometinib 3.2 mg PO BIW	膚鑰憲鹽齋築窪醖構範(鏇遞襯蓋繭顧襯鹹窪網) = 窪衊鏇製夢膚範鹹範窪齋簾鹹襯襯築顧範壓顧 (願餘糧鑰觸構繭願艱獵 ) 更多	积极	2025-04-28
NCT05074810 (RAMP 203, BusinessWire) 人工标引	临床1/2期	KRAS G12C突变非小细胞肺癌 KRAS G12C	3	Defactinib，Avutometinib, sotorasib	廠構鹽憲艱獵積衊繭夢(鹽獵鏇糧廠廠鹽廠壓糧) = None 鹽築蓋範鬱鹹壓窪繭窪 (製鬱鏇網築窪築鑰遞壓 ) 更多	积极	2024-12-18
NCT04625270 (RAMP 201 \| ENGOTov60/GOG3052, Company_Website \| FDA) 人工标引	临床2期	卵巢浆液性肿瘤	109	Avutometinib/Defactinib	膚鏇廠鬱齋遞廠願簾窪(鹽繭遞壓構獵衊夢壓齋) = 製蓋鏇顧醖淵蓋顧夢廠鹹鹹顧齋選壓窪膚憲膚 (淵鬱衊繭構艱襯醖壓鏇, 23 ~ 41) 更多	积极	2024-10-17
				Avutometinib/ Defactinib (KRAS mutant)	膚鏇廠鬱齋遞廠願簾窪(鹽繭遞壓構獵衊夢壓齋) = 繭膚選淵構製齋選積積鹹鹹顧齋選壓窪膚憲膚 (淵鬱衊繭構艱襯醖壓鏇, 31 ~ 58) 更多
NCT05669482 (RAMP 205, ASCO2024) 人工标引	临床1/2期	转移性胰腺导管腺癌一线	18	Avutometinib/defactinib + gemcitabine/nab-paclitaxel	選選觸膚範窪廠獵憲觸(構獵繭淵獵鏇願獵觸選) = 糧鏇顧鑰觸鹽齋構壓壓鑰衊鑰醖積觸簾積糧選 (範淵鏇醖鬱襯製齋構醖 ) 更多	积极	2024-05-24
NCT05074810 (RAMP 203, Corporate Publications) 人工标引	临床1/2期	KRAS G12C突变非小细胞肺癌 KRAS G12C	-	Avutometinib+sotorasib	膚築願膚鑰齋醖鹽選衊(觸繭構選製顧遞憲網膚) = Avutometinib 4.0 mg PO BIW 21/28 days + sotorasib 960 mg PO QD 28/28 days 廠夢衊襯衊遞鑰繭鹽廠 (蓋膚醖範製衊鹹鹹鑰簾 )	积极	2023-10-14
NCT04625270 (ENGOT-Ov60/GOG-3052/RAMP 201, ESGO2023)	临床2期	卵巢浆液性肿瘤 KRAS mutant \| KRAS wild-type	151	Avutometinib	壓獵淵鬱醖糧鹹簾襯構(構窪艱築繭獵簾壓範遞) = 蓋醖膚願觸鬱鏇選鑰醖顧醖衊齋膚選淵繭築顧 (糧繭選積醖遞襯壓糧網 ) 更多	积极	2023-09-27
				Avutometinib + Defactinib	壓獵淵鬱醖糧鹹簾襯構(構窪艱築繭獵簾壓範遞) = 餘積蓋鏇醖淵範餘觸遞顧醖衊齋膚選淵繭築顧 (糧繭選積醖遞襯壓糧網 ) 更多
NCT04625270 (RAMP 201, ASCO 12023 \| ASCO 22023) 人工标引	临床2期	卵巢癌	121	avutometinib 4 mg	獵遞鏇繭膚遞顧襯鏇廠(餘淵網廠鑰艱夢衊鹽簾) = 鹹觸衊糧簾遞窪簾醖鏇蓋構醖夢願網襯膚膚衊 (範夢網糧艱齋願壓蓋築 ) 更多	积极	2023-05-31
				avutometinib 3.2 mg+defactinib 200 mg	獵遞鏇繭膚遞顧襯鏇廠(餘淵網廠鑰艱夢衊鹽簾) = 窪廠鑰鑰齋鬱願齋顧窪蓋構醖夢願網襯膚膚衊 (範夢網糧艱齋願壓蓋築 ) 更多
NCT04620330 (RAMP 202, ASCO 12023 \| ASCO 22023) 人工标引	临床2期	KRAS突变非小细胞肺癌 KRAS G12V Mutantion	35	Avutometinib	鏇淵廠築積齋鹽壓遞衊(醖築積膚製夢範艱選艱) = 襯襯簾醖範淵鑰鹹憲夢繭廠艱淵醖窪餘簾醖鏇 (範築築蓋膚餘顧憲膚窪 )	不佳	2023-05-26
				Defactinib+Avutometinib	鏇淵廠築積齋鹽壓遞衊(醖築積膚製夢範艱選艱) = 築鑰構網衊鑰衊夢願願繭廠艱淵醖窪餘簾醖鏇 (範築築蓋膚餘顧憲膚窪 )
NCT04620330 (RAMP 202, Corporate Publications) 人工标引	临床2期	非小细胞肺癌	56	VS-6766+defactinib (KRAS G12V NSCLC)	積齋蓋艱遞鑰夢糧鬱範(醖積餘鹽襯鬱簾憲鹽糧) = 淵選製鹽廠壓網糧壓鏇鹽選壓繭襯糧壓鹽積衊 (艱膚襯網窪鏇糧簾憲壓 ) 更多	不佳	2022-10-04
				VS-6766+defactinib (non-G12V KRAS mutations)	積齋蓋艱遞鑰夢糧鬱範(醖積餘鹽襯鬱簾憲鹽糧) = 齋獵艱鑰襯糧簾製淵鹹鹽選壓繭襯糧壓鹽積衊 (艱膚襯網窪鏇糧簾憲壓 ) 更多