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

/ Active, not 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.

2025-09-01·JOURNAL OF CLINICAL ONCOLOGY

Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201

Article

作者: Colombo, Nicoletta ; Monk, Bradley J. ; Thaker, Premal H. ; Santin, Alessandro D. ; Newman, Gregg ; Prendergast, Emily ; Moore, Kathleen N. ; Oaknin, Ana ; O'Malley, David M. ; Van Nieuwenhuysen, Els ; Banerjee, Susana N. ; Lustgarten, Stephanie ; Chon, Hye Sook ; Aghajanian, Carol ; Gennigens, Christine ; D'Hondt, Véronique ; Holloway, Robert W. ; Van Gorp, Toon ; Ring, Kari ; Clamp, Andrew ; Grisham, Rachel N. ; Youssoufian, Hagop ; Gourley, Charlie ; Salinas, Erin ; Rodrigues, Manuel

PURPOSE:

This study evaluated the efficacy and safety of avutometinib (rapidly accelerated fibrosarcoma/mitogen-activated extracellular signal-regulated kinase [MEK] clamp) alone or in combination with defactinib (focal adhesion kinase inhibitor) in patients with recurrent low-grade serous ovarian cancer (LGSOC).

METHODS:

In this phase II, open-label study, patients with recurrent, measurable LGSOC after ≥1 line of platinum chemotherapy were stratified by tumor Kirsten rat sarcoma virus homolog ( KRAS ) mutation status and randomly assigned to oral avutometinib 4.0 mg two times per week monotherapy or avutometinib 3.2 mg two times per week in combination with oral defactinib 200 mg two times per day. The combination was selected as the go-forward regimen for expansion. The primary end point was objective response rate (ORR) by blinded independent central review.

RESULTS:

A total of 115 patients received the go-forward combination regimen. Patients had a median of 3 (range, 1-9) prior lines of therapy, including hormonal (86%), bevacizumab (51%), and MEK inhibitor (22%). Confirmed ORR was 31% (95% CI, 23% to 41%) with a median duration of response of 31.1 months (95% CI, 14.8 to 31.1). ORR was 44% in KRAS- mutant and 17% in KRAS wild-type cohorts. The median progression-free survival was 12.9 months (95% CI, 10.9 to 20.2) overall and 22.0 months (95% CI, 11.1 to 36.6) and 12.8 months (95% CI, 7.4 to 18.4) in KRAS- mutant and wild-type cohorts, respectively. The most frequent grade ≥3 treatment-related adverse events (AEs) were elevated creatine phosphokinase (24%), diarrhea (8%), and anemia (5%). Ten percent of patients discontinued because of AEs.

CONCLUSION:

The efficacy and safety profile of avutometinib in combination with defactinib support this combination as a potential standard of care for recurrent LGSOC. A randomized phase 3 study of avutometinib and defactinib versus investigator's choice of therapy for women with recurrent LGSOC is currently enrolling (RAMP301; ClinicalTrials.gov identifier: NCT06072781 ).

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.

118

项与 Avutometinib 相关的新闻（医药）

2025-09-09

·EINPresswire

LGSOC Awareness Day: Breakthrough FDA Approval Marks Hope for 80,000 Women

LGSOC Awareness Day 2025: A breakthrough FDA approval proves rare cancers deserve focus, funding, and a future of hope. This FDA approval proves what we’ve always believed: when rare cancers get the focus they deserve, breakthroughs follow.” — Emily Campbell MIAMI, FL, UNITED STATES, September 9, 2025 / EINPresswire.com / -- September 9 marks the second annual Low-Grade Serous Ovarian Cancer (LGSOC) Awareness Day. But 2025 isn't just another awareness campaign. It’s the year a community of advocates came together to make change. Low-grade serous ovarian cancer affects 6,000 to 8,000 women in the U.S. and 80,000 worldwide every year. LGSOC strikes younger women with a median age of 45 versus 63 for high-grade ovarian cancer, yet it has historically received a fraction of research attention and funding. The research tells a stark story: chemotherapy for LGSOC has low success rates — only 4% of patients responded when treated before surgery and 25% when treated after surgery. For every 100 people diagnosed, more than 80 will have their cancer come back. Yet until this year, there were zero FDA-approved treatments specifically designed for LGSOC. At Not These Ovaries , we see these numbers as more than statistics. They represent thousands of women who deserved better, faster answers. The moment that changed everything Last May, medical history was made. The FDA granted accelerated approval to avutometinib and defactinib (Avmapki Fakzynja Co-Pack), the first-ever treatment approved for LGSOC patients, specifically for recurrence with KRAS mutations. But here's what's critical: this approval comes with specific requirements. The FDA approved this treatment specifically for adult patients who meet the following criteria: - Have low-grade serous ovarian cancer (LGSOC) - Have recurrent disease (cancer that has returned after prior treatment) - Have a confirmed KRAS mutation in their tumor (this is a critical requirement) - Have received prior systemic therapy Without a confirmed KRAS mutation, patients cannot access this breakthrough treatment. This makes genetic testing not just helpful, but crucial for treatment decisions. The Phase 2 RAMP 201 trial demonstrated a remarkable 44% overall response rate in KRAS-mutated patients, with responses lasting anywhere from 3.3 to 31.1 months. This breakthrough targets approximately 30% of LGSOC patients who carry KRAS mutations, transforming their journey from "managing with treatments designed for other cancers" to accessing purpose-built therapy. Why this matters beyond the medicine This isn't just about one drug. It's validation that LGSOC deserves recognition as a distinct disease requiring specialized research and targeted treatments. For too long, LGSOC patients received what we call "treatment leftovers" and off-label use of medication: therapies designed for other cancers, with limited effectiveness. This approval proves that when you fund research specifically for rare diseases, breakthroughs follow. And when patient communities partner with researchers who listen, we can accelerate progress that seemed impossible just years ago. What comes next The ongoing Phase 3 RAMP 301 trial is evaluating this combination in broader LGSOC populations, both with and without KRAS mutations. This could potentially expand treatment options for even more patients, which is exactly why continued research funding matters. For the 90% of LGSOC patients who report that their lives "revolve around cancer," this approval offers something revolutionary: the possibility that effective treatment might allow life to revolve around living instead. Action steps for LGSOC Awareness Day This LGSOC Awareness Day, here's how you can drive real change: - Share life-saving awareness: The symptoms of LGSOC — persistent bloating, pelvic pain, feeling full quickly, urinary urgency, and abdominal discomfort — shouldn't be dismissed, especially in younger women. Share these symptoms widely. - Fund research that happens now: Organizations like Not These Ovaries fund clinical trials that start immediately. Your donation today goes 100% toward research, not overhead. - Advocate for genetic testing: KRAS mutation testing is now critical for LGSOC treatment decisions. Ensure patients know to request comprehensive tumor profiling, not just basic genetic screening. - Connect patients with specialists: Link people to gynecologic oncologists experienced in rare ovarian cancer subtypes and LGSOC-specific support networks. Action and understanding will save lives Today, we celebrate a medical milestone that seemed impossible just years ago. Tomorrow, we continue working toward a future where no LGSOC patient faces their diagnosis feeling alone, uninformed, or without hope. The approval of avutometinib and defactinib proves our core belief: when rare diseases receive focused attention and urgent funding, breakthrough treatments follow. This LGSOC Awareness Day, we're not just raising awareness; we're demonstrating that advocacy, research, and swift action can literally save lives. The question isn't whether we can develop treatments for rare cancers. This approval proves we can. The question is: how fast can we fund the next breakthrough? Chris Campbell Not These Ovaries impact@nottheseovaries.org Visit us on social media: LinkedIn Instagram Facebook YouTube X Frequently Asked Questions about LGSOC 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.

临床结果临床2期临床3期上市批准加速审批

2025-09-03

·医药观澜

破局之路：从50%死亡率，到生存率接近翻倍，卵巢癌治疗如何实现历史性跨越

编者按：卵巢癌是死亡率最高的妇科癌症之一。从手术到放化疗，再到创新靶向疗法，医学的进步持续为广泛的卵巢癌患者带来新的治疗选择。然而，临床挑战仍在：晚期卵巢癌患者的五年生存率仍未突破50%的大关。目前，全球有数百新药管线项目处于临床研究阶段，不断探索卵巢癌治疗的更多可能性。作为医药创新的赋能者，药明康德凭借一体化、端到端的CRDMO平台，持续助力全球合作伙伴加速包括卵巢癌在内的各类癌症创新药物的研发进程，致力于将更多突破性治疗方案带给癌症患者，为战胜癌症贡献力量。在全球女性癌症谱系中，卵巢癌一直以“难治”著称。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。卵巢癌的治疗策略经历了漫长的演变。从19世纪早期的开创性手术起步，当时卵巢切除术因缺乏有效的技术支持而风险极高；但在十九世纪后期，随着无菌技术和麻醉的应用，该手术的死亡率从惊人的50%大幅降至11%，成为治疗史上的重要转折。此后，医学的进步持续推动治疗策略的演进：20世纪中期引入放射治疗，70-80年代铂类与紫杉烷类化疗药物问世，直再到21世纪靶向治疗创新，每一步都为卵巢癌的治疗带来了深刻改变。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。回望整个卵巢癌治疗的发展史，各类治疗手段的迭代演进，全球各界协同创新，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“无差别杀伤”到“精准打击” 自从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。临床上仍然存在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——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。 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，贝伐珠单抗能暂时延缓疾病进展，但难以显著延长患者的总生存时间，加上该药有可能引发一些不良反应，医学界希望找到更安全有效的新疗法。 “合成致死”，针对卵巢癌的常见突变 2014年，随着首款PARP抑制剂的问世为卵巢癌治疗带来了革命性转变。这一突破可追溯至1922年，当时哥伦比亚大学Calvin Bridges博士发现了“合成致死”现象——既两个基因同时发生突变时会导致细胞死亡，而单独突变却不会。近一个世纪后，这一机制成为了抗癌药物开发的新思路。2005年，《自然》杂志同期发表两项里程碑研究首次证实：PARP抑制剂与BRCA突变存在“合成致死”效应。其原理在于，BRCA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。当两种机制同时被抑制时，癌细胞就会因无法修复DNA损伤而死亡。约15%的卵巢癌患者携带BRCA基因突变，这为PARP抑制剂的应用提供了理想靶点。经过近十年的临床探索，2014年12月，FDA批准了首款PARP抑制剂Lynparza（olaparib，奥拉帕利），用于治疗携带BRCA种系突变的晚期卵巢癌患者。奥拉帕利的成功推动了更多PARP抑制剂的研发。2016年，Zejula（niraparib，尼拉帕利）证实其对同源重组修复缺陷（HRD）阳性的非BRCA突变患者同样有效，进一步扩大了受益人群。截至目前，全球已有7款PARP抑制剂获批，其中6款可用于治疗卵巢癌，包括奥拉帕利、尼拉帕利，塞纳帕利、帕米帕利、氟唑帕利，以及和Rubraca（rucaparib）。它们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PARP抑制剂广泛应用于在一线维持治疗，卵巢癌患者的生存率持续提升。例如，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%。这一进步源于多方面的协同进展：更彻底的手术肿瘤减灭，更有效的化疗方案，PARP抑制剂的维持治疗的精准应用，以及其他靶向药物的合理组合，共同延缓了疾病复发的进程。从靶向药到免疫疗法在PARP抑制剂取得显著临床成果的同时，多种机制各异的卵巢癌创新疗法也陆续问世，为患者提供了更加丰富的治疗选择。以叶酸受体α（FRα）为例，尽管该靶点在35-40%的卵巢癌中存在高表达，但长期以来缺乏有效靶向药物。2022年11月，FDA加速批准了首个靶向FRα的抗体偶联药物（ADC）Elahere（mirvetuximab soravtansine）。该药物通过将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杀伤打击。值得一提的是，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）获益的疗法：在其关键3期临床中，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个月延长近4个月。针对化疗应答率较低的卵巢癌亚型，2025年5月，FDA加速批准了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可同时抑制RAF和MEK，克服了传统MEK抑制剂的代偿性激活问题。在抗血管生成治疗方面，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，苏维西塔单抗组显示出总生存期获益趋势（16.07个月 vs 14.88个月）。此外，该药物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种类限制。除上述靶点外，约1-2%的卵巢癌患者携带NTRK基因融合突变，该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）能够阻断突变NTRK基因产生异常蛋白质，适用于那些经治后进展、携带NTRK基因突变的晚期卵巢癌患者。在靶向疗法不断突破的同时，免疫治疗也为卵巢癌患者带来新的希望。癌细胞常利用免疫“检查点”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。目前，包括Keytruda（pembrolizumab，帕博利珠单抗）、Jemperli（dostarlimab）和百泽安（替雷利珠单抗）在内的多种PD-1抑制剂已获得监管批准，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。靶向治疗与免疫疗法的持续涌现，正推动卵巢癌治疗迈向精准化和个体化的新时代。随着对卵巢癌分子机制理解的深入以及创新药物的不断研发，临床医生得以依据患者的分子特征，选择更加匹配的治疗策略，为不同亚型的卵巢癌患者提供更具针对性的治疗选择。一体化平台赋能卵巢癌新药开发从十九世纪的卵巢切除术发展至如今的精准靶向治疗，人类对抗卵巢癌的征程已走过一条漫长而艰辛的道路。一方面看，治疗手段不断革新，给患者带来了新的希望。然而另一方面，晚期卵巢癌患者的五年生存率至今仍未突破50%。这一现实始终提醒我们：与卵巢癌这一“沉默杀手”的较量，依然任重而道远。根据公开资料，目前有数百卵巢癌疗法研发管线已进入临床开发阶段。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。我们很高兴能赋能来自全球客户的卵巢癌新药的开发，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！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。

放射疗法

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

100 项与 Avutometinib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15254

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	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
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
转移性结直肠癌	临床2期	美国	Verastem, Inc.	2022-08-22
晚期癌症	临床2期	美国	Verastem, Inc.	2022-08-01

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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	鏇鑰廠範願廠襯憲醖膚(糧構積夢糧願艱蓋夢鏇) = 41% 鑰壓醖鏇艱衊蓋製顧膚 (淵糧鹹膚願淵遞築製憲 ) 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	壓餘遞繭夢鬱繭簾製糧(鬱鏇簾製選膚壓範築廠) = 製醖願積夢鹹範餘製築艱淵繭鹽膚襯廠衊範憲 (網艱鬱衊蓋遞製製齋鏇 ) 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	積壓鹹簾鏇夢醖鑰願構(遞簾夢選願糧壓鹹艱築) = None 膚鑰餘簾鬱鹹淵築窪窪 (壓衊衊衊鹽鹹構糧願醖 ) 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	築積鑰鹽夢鹹範範壓襯(範選壓艱選艱選膚繭餘) = 製鬱積糧襯齋廠襯鹽願憲夢網艱窪廠壓築鏇鹽 (膚壓遞廠餘鑰齋網製網, 23 ~ 41) 更多	积极	2024-10-17
				Avutometinib/ Defactinib (KRAS mutant)	築積鑰鹽夢鹹範範壓襯(範選壓艱選艱選膚繭餘) = 齋簾衊鹽夢選觸選鑰繭憲夢網艱窪廠壓築鏇鹽 (膚壓遞廠餘鑰齋網製網, 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	AvutometinibAvutometinib/defactinib + gemcitabine/nab-paclitaxel	鏇餘淵觸餘觸製獵選鹹(製醖艱鑰壓獵構壓憲鑰) = 鏇憲遞廠鑰餘願憲齋鑰艱繭鹽憲夢窪築糧餘構 (築齋蓋獵廠齋鏇憲簾窪 ) 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	衊糧壓齋網糧願範鏇製(構積餘遞夢範餘簾蓋選) = Avutometinib 4.0 mg PO BIW 21/28 days + sotorasib 960 mg PO QD 28/28 days 糧廠餘餘鏇選醖餘構願 (壓淵醖獵憲選壓廠壓齋 )	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	鏇蓋構襯顧餘夢遞夢遞(範夢壓遞顧築網淵選壓) = 壓齋醖糧製膚餘願憲醖製範窪淵齋壓淵糧積鑰 (選願夢衊窪糧餘簾選鹹 ) 更多	积极	2023-09-27
				Avutometinib + Defactinib	鏇蓋構襯顧餘夢遞夢遞(範夢壓遞顧築網淵選壓) = 鹽廠顧夢憲選衊繭範繭製範窪淵齋壓淵糧積鑰 (選願夢衊窪糧餘簾選鹹 ) 更多
NCT04625270 (RAMP 201, ASCO 12023 \| ASCO 22023) 人工标引	临床2期	卵巢癌	121	avutometinib 4 mg	艱獵獵鬱淵築壓膚築顧(選膚蓋憲製鹽廠繭製衊) = 廠網糧鏇窪範襯淵觸願積顧簾願窪獵齋遞獵範 (醖淵觸鹽觸鹹鏇蓋製願 ) 更多	积极	2023-05-31
				avutometinib 3.2 mg+defactinib 200 mg	艱獵獵鬱淵築壓膚築顧(選膚蓋憲製鹽廠繭製衊) = 築鏇簾繭壓簾膚觸範獵積顧簾願窪獵齋遞獵範 (醖淵觸鹽觸鹹鏇蓋製願 ) 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	選蓋築齋願壓鑰鏇糧繭(鬱襯蓋選窪構積願鏇糧) = 鬱夢憲衊簾鏇築廠獵鏇繭網遞構糧壓鏇窪製齋 (築繭築鬱繭網鬱襯夢鹹 )	不佳	2023-05-26
				Defactinib+Avutometinib	選蓋築齋願壓鑰鏇糧繭(鬱襯蓋選窪構積願鏇糧) = 壓衊襯願獵繭壓鑰鏇遞繭網遞構糧壓鏇窪製齋 (築繭築鬱繭網鬱襯夢鹹 )
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)	鬱淵蓋選糧範壓鏇觸繭(艱襯鏇顧願製積鏇製壓) = 齋蓋選繭糧鑰繭範觸鑰鹽憲願鹹夢構餘鑰壓膚 (積襯窪窪鹹築範衊構衊 ) 更多	不佳	2022-10-04
				VS-6766+defactinib (non-G12V KRAS mutations)	鬱淵蓋選糧範壓鏇觸繭(艱襯鏇顧願製積鏇製壓) = 鏇鹽願壓繭製蓋憲衊鑰鹽憲願鹹夢構餘鑰壓膚 (積襯窪窪鹹築範衊構衊 ) 更多