Open-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer

To learn if avutometinib in combination with defactinib and cetuximab can help to control unresectable, anti-EGFR-refractory, advanced colorectal cancer.

开始日期2024-10-31

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT06394804 / Recruiting临床2期IIT

Combination Targeted and Hormonal treAtMEnt of Low-gradE Serous Ovarian Cancer in the upfroNt Setting

The researchers are doing this study to find out whether the combination of avutometinib, defactinib, and letrozole is an effective treatment for people with low-grade serous ovarian cancer (LGSOC). The researchers will also look at the safety of this combination.

开始日期2024-04-29

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

NCT06072781 / Recruiting临床3期

A Phase 3, Randomized, Open-Label Study of Combination Therapy With Avutometinib Plus Defactinib Versus Investigator's Choice of Treatment in Patients With Recurrent Low-Grade Serous Ovarian Cancer (LGSOC) (RAMP 301)

This study will assess the safety and efficacy of avutometinib (VS-6766) in combination with defactinib versus Investigator's choice of treatments (ICT) in subjects with recurrent LGSOC who have progressed on a prior platinum-based therapy.

开始日期2024-03-18

申办/合作机构

Verastem, Inc.

[+2]

100 项与 Defactinib 相关的临床结果

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100 项与 Defactinib 相关的转化医学

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100 项与 Defactinib 相关的专利（医药）

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项与 Defactinib 相关的文献（医药）

2024-01-01·Theranostics

Annotation of CD8⁺ T-cell function via ICAM-1 imaging identifies FAK inhibition as an adjuvant to augment the antitumor immunity of radiotherapy

Article

作者: Yang, Zhi ; Wang, Yanpu ; Zhou, Haoyi ; Zhang, Weifang ; Song, Rui ; Li, Kui ; Zhao, Yang ; Zhang, Ting ; Wang, Feng ; Zhou, Shixin ; Zhao, Meixin ; Liu, Zhaofei ; Zhang, Yining ; Zhu, Hua

Background: Radiotherapy (RT) may trigger systemic antitumor immunity, manifesting as regression of non-irradiated lesions (abscopal effect). Intracellular adhesion molecule-1 (ICAM-1) is a key molecule involved in the abscopal effect of RT. However, the specific function of ICAM-1 in CD8⁺ T cells during antitumor immune responses remains unclear. Herein, we investigated whether noninvasive imaging of ICAM-1 can be used to annotate CD8⁺ T-cell function, thereby better selecting combinational therapy to enhance the antitumor immunity induced by RT. Methods: Using knockout mouse models, we investigated the role of ICAM-1 expressed on CD8⁺ T cells in the antitumor immunity of RT and conducted drug screening guided by ICAM-1-targeted noninvasive imaging. Results: The systemic antitumor effect of RT relies on the expression of ICAM-1 on CD8⁺ T cells. ICAM-1 expression is essential for CD8⁺ T-cell activation, proliferation, and effector function. Noninvasive annotation of the proliferation and effector function of CD8⁺ T cells by ICAM-1-targeted imaging identified VS-6063, a focal adhesion kinase inhibitor, as a new adjuvant to augment systemic antitumor immunity of RT in an immunologically "cold" tumor model. Mechanistically, VS-6063 overcomes the physical barriers in tumors and promotes the migration and infiltration of CD8⁺ T cells primed by RT into distant tumors. Conclusion: Our findings highlight that molecular imaging of ICAM-1 levels provides a dynamic readout of the proliferation and effector function of tumor-infiltrating CD8⁺ T cells, which facilitates the high-throughput exploitation of new combinational drugs to maximize the systemic antitumor effect of RT.

2023-12-12·Journal of biomolecular structure & dynamics

Identification of defactinib derivatives targeting focal adhesion kinase using ensemble docking, molecular dynamics simulations and binding free energy calculations

Article

作者: Shi, Mingsong ; Guo, Chuan ; Xia, Xun ; Xiao, Jiujia ; Li, Qinxuan ; Ma, Feng

Focal adhesion kinase (FAK) belongs to the nonreceptor tyrosine kinases, which selectively phosphorylate tyrosine residues on substrate proteins. FAK is associated with bladder, esophageal, gastric, neck, breast, ovarian and lung cancers. Thus, FAK has been considered as a potential target for tumor treatment. Currently, there are six adenosine triphosphate (ATP)-competitive FAK inhibitors tested in clinical trials but no approved inhibitors targeting FAK. Defactinib (VS-6063) is a second-generation FAK inhibitor with an IC₅₀ of 0.6 nM. The binding model of VS-6063 with FAK may provide a reference model for developing new antitumor FAK-targeting drugs. In this study, the VS-6063/FAK binding model was constructed using ensemble docking and molecular dynamics simulations. Furthermore, the molecular mechanics/generalized Born (GB) surface area (MM/GBSA) method was employed to estimate the binding free energy between VS-6063 and FAK. The key residues involved in VS-6063/FAK binding were also determined using per-residue energy decomposition analysis. Based on the binding model, VS-6063 could be separated into seven regions to enhance its binding affinity with FAK. Meanwhile, 60 novel defactinib-based compounds were designed and verified using ensemble docking. Overall, the present study improves our understanding of the binding mechanism of human FAK with VS-6063 and provides new insights into future drug designs targeting FAK.Communicated by Ramaswamy H. Sarma.

2023-11-14·Clinical cancer research : an official journal of the American Association for Cancer Research

Correction: Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: a Phase I Dose Escalation and Expansion Study

作者: Suresh, Rama ; Hawkins, William G ; Zhu, Mojun ; Aranha, Olivia ; Belle, Jad I ; Lim, Kian-Huat ; Trikalinos, Nikolaos A ; Acharya, Abhi ; Herzog, Brett H ; Ratner, Lee ; Yoon, Harry H ; DeNardo, David G ; Bogner, Savannah J ; Brown, Amberly ; Breden, Marcus ; Herndon, John ; Wang-Gillam, Andrea ; Boice, Nicholas ; Tan, Benjamin ; Abdiannia, Mina ; Pedersen, Katrina ; Gao, Feng ; McWilliams, Robert ; Lockhart, Albert C

项与 Defactinib 相关的新闻（医药）

2024-07-01

·BioSpace

Verastem Oncology Announces Addition to Russell 3000® and Russell Microcap® Indexes

BOSTON--(BUSINESS WIRE)-- Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, today announced that in connection with the 2024 Russell U.S. Indexes annual reconstitution, the company will be added to the Russell 3000® and Russell Microcap® Indexes, effective at the open of U.S. equity markets today, Monday, July 1, 2024. “The recognition and increased exposure of being added to the Russell Indexes underscore the recent progress we’ve made across our pipeline, which includes bringing avutometinib in combination with defactinib one step closer to being a potential new treatment option for patients with recurrent low-grade serous ovarian cancer in the U.S.,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “We remain on track to announce mature data from RAMP 201 and complete our rolling NDA submission in the second half of 2024 while advancing our other clinical programs in metastatic pancreatic cancer and non-small cell lung cancer. Now that GenFleet has initiated the Phase 1/2 clinical trial in China for GFH375/VS-7375, a potent and selective oral KRAS G12D (ON/OFF) inhibitor, we look forward to leveraging this data to accelerate a path forward in the U.S. and rest of world.” The annual Russell indexes reconstitution captures the 4,000 largest U.S. stocks as of Thursday, April 30, 2024, ranking them by total market capitalization. Russell indexes are widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. According to the data as of the end of December 2023, about $10.5 trillion assets are benchmarked against the Russell U.S. indexes, which belong to FTSE Russell, a prominent global index provider. For more information on the Russell 3000® Index and the Russell indexes reconstitution, go to the “Russell Reconstitution” section of the FTSE Russell website. About Verastem Oncology Verastem Oncology (Nasdaq: VSTM) is a late-stage development biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on RAS/MAPK-driven cancers, specifically novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and FAK inhibition. For more information, please visit and follow us on LinkedIn. About FTSE Russell FTSE Russell is a leading global provider of benchmarking, analytics, and data solutions for investors, giving them a precise view of the market relevant to their investment process. A comprehensive range of reliable and accurate indexes provides investors worldwide with the tools they require to measure and benchmark markets across asset classes, styles, or strategies. FTSE Russell index expertise and products are used extensively by institutional and retail investors globally. For over 30 years, leading asset owners, asset managers, ETF providers and investment banks have chosen FTSE Russell indexes to benchmark their investment performance and create ETFs, structured products, and index-based derivatives. FTSE Russell is focused on applying the highest industry standards in index design and governance, employing transparent rules-based methodology informed by independent committees of leading market participants. FTSE Russell fully embraces the IOSCO Principles, and its Statement of Compliance has received independent assurance. Index innovation is driven by client needs and customer partnerships, allowing FTSE Russell to continually enhance the breadth, depth and reach of its offering. FTSE Russell is wholly owned by London Stock Exchange Group. For more information, visit . Forward Looking Statements This press release includes forward-looking statements about, among other things, Verastem Oncology’s programs and product candidates, strategy, future plans and prospects, including statements related to the impact of the company’s addition to the Russell 3000® and Russell Microcap® Indexes, the expected outcome and benefits of collaborations, including with GenFleet Therapeutics (Shanghai), Inc. (“GenFleet”), the timing of commencing and completing trials, including topline data reports, interactions with regulators, the potential for the commercialization of product candidates and potential for additional development programs involving Verastem Oncology’s lead compound. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," "can, " "promising" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the development and potential commercialization of our product candidates, including avutometinib in combination with other compounds, including defactinib, LUMAKRAS and others; the uncertainties inherent in research and development, such as negative or unexpected results of clinical trials, the occurrence or timing of applications for our product candidates that may be filed with regulatory authorities in any jurisdictions; whether and when regulatory authorities in any jurisdictions may approve any such applications that may be filed for our product candidates, and, if approved, whether our product candidates will be commercially successful in such jurisdictions; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding trial design, labeling and other matters that could affect the timing, availability or commercial potential of our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from clinical trials will be predictive of the results or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is uncertain; the market opportunities of our drug candidates are based on internal and third-party estimates which may prove to be incorrect; that third-party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that enrollment of clinical trials may take longer than expected, which may delay our development programs, including delays in submission or review by the FDA of our NDA submission in recurrent KRAS mutant LGSOC if enrollment in our confirmatory trial is not well underway at the time of submission; that our product candidates will cause adverse safety events and/or unexpected concerns may arise from additional data or analysis, or result in unmanageable safety profiles as compared to their levels of efficacy; that we maybe unable to successfully validate, develop and obtain regulatory approval for companion diagnostic tests for our product candidates that require or would commercially benefit from such tests, or experience significant delays in doing so; that the mature RAMP 201 data and associated discussions with the FDA may not support the scope of our rolling NDA submission for the avutometinib and defactinib combination in LGSOC, including with respect to KRAS wild type LGSOC; that our product candidates may experience manufacturing or supply interruptions or failures; that any of our third-party contract research organizations, contract manufacturing organizations, clinical sites, or contractors, among others, who we rely on fail to fully perform; that we face substantial competition, which may result in others developing or commercializing products before or more successfully than we do which could result in reduced market share or market potential for our product candidates; that we will be unable to successfully initiate or complete the clinical development and eventual commercialization of our product candidates; that the development and commercialization of our product candidates will take longer or cost more than planned, including as a result of conducting additional studies or our decisions regarding execution of such commercialization; that we may not have sufficient cash to fund our contemplated operations , including certain of our product development programs; that we may not attract and retain high quality personnel; that we or Chugai Pharmaceutical Co., Ltd. will fail to fully perform under the avutometinib license agreement; that our total addressable and target markets for our product candidates might be smaller than we are presently estimating; that Secura Bio, Inc. will fail to fully perform under the asset purchase agreement with Secura Bio, Inc., including in relation to milestone payments; that we will not see a return on investment on the payments we have and may continue to make pursuant to the collaboration and option agreement with GenFleet or that GenFleet will fail to fully perform under the agreement; that we may not be able to establish new or expand on existing collaborations or partnerships, including with respect to in-licensing of our product candidates, on favorable terms, or at all; that we may be unable to obtain adequate financing in the future through product licensing, co-promotional arrangements, public or private equity, debt financing or otherwise; that we will not pursue or submit regulatory filings for our product candidates; and that our product candidates will not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients. As a result of these and other factors, we may not achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (SEC) on March 14, 2024, and in any subsequent filings with the SEC, which are available at and .

2024-06-13

·同写意

ASCO 2024，寻找掌声的方向

同写意20周年大会：中国医药创新未来之路！“意”同创新，穿越周期，赢取未来。7月中旬，苏州金鸡湖畔，让我们与“新药写意人”一起为中国医药创新“同写意”！每年的ASCO，总有那么几瞬，明星药物与破冰时刻交相辉映，共同成为全球肿瘤研发瞩目的闪光点。 2022年，DS-8201的DESTINY-Breast 04研究结果发布现场，罕见出现全场起立鼓掌的一幕。时隔两年，辉瑞的洛拉替尼、阿斯利康的奥希替尼在肺癌领域的研究，再次赢得了满堂彩。颠覆现有疗法，甚至重新定义疾病治疗的潜力，是它们赢得掌声的根本。而不同之处在于，DS-8201的横空出世，本质是将ADC技术彻彻底底地推向了前台，开启了ADC盛世，而无论洛拉替尼还是奥希替尼，似乎并没有为市场带来新的方向。新疗法与技术的每一次跃进，都是对生命奥秘的深层叩问，牵动着未来的治疗图景。而这一次，纵观整个ASCO大会，关于肿瘤免疫、靶向治疗似乎没有太多令人兴奋的颠覆变化。但平静之下，涌动着变革的潜流，下一波药物创新的浪潮已在ADC、双抗、KRAS等阵地蓄势待发。特别是在ADC的最前沿，中国药企的身影日益活跃，彰显着不容小觑的新兴力量。每一次变局的前夜，都孕育着未来的轮廓。ASCO的舞台，正是这无数次迭代故事的见证者。而这一次，我们期待中国创新力量的深度介入，于世界舞台绽放光彩。 1 为“重新定义”而响 ASCO会议第一天，芝加哥会展中心座无虚席的“Arie皇冠剧院”，来自澳洲的Benjamin Solomon教授，刚刚开始演讲，会场便响起了持久的掌声。原因在于，其口头报告了洛拉替尼一线治疗ALK阳性非小细胞肺癌（NSCLC）的CROWN研究5年随访数据。数据显示，洛拉替尼组患者5年无进展生存率60%，中位无进展生存期仍未达到。随访5年仍没有达到中位无进展生存期，这不仅是单药靶向治疗在晚期NSCLC领域，更是整个实体瘤领域目前取得的最长的PFS，患者生存获益史无前例。对于晚期肺癌患者来说，一线药物所带来的总生存期（OS）及无进展生存期（PFS）延长，是患者“长生存”的关键治疗窗口。而在临床中，通常将“5年生存且无进展复发”定义为“临床治愈”。尽管这并不代表彻底安全，但洛拉替尼依然立下了一个新的里程碑。因为，在此之前，临床治愈几乎是晚期NSCLC患者无法企及的梦想。目前，洛拉替尼的PFS率每年仅降低2%左右，按照这一趋势发展，ALK阳性晚期NSCLC患者的PFS将有望超过10年。这样的临床获益趋势，无疑进一步会改变ALK阳性NSCLC一线治疗格局。会议第三天，另一项来自肺癌领域的研究，再次获得全场掌声，研究者的发言甚至两次被掌声所打断。阿斯利康公布的LAURA III期临床试验中，与安慰剂相比，奥希替尼将EGFR突变的III期不可切除肺癌患者的疾病进展或死亡风险降低了84%。这是首个也是唯一一个在III期肺癌临床研究中显示出生存获益的EGFR抑制剂和靶向治疗方案，能够将无进展生存期延长三年以上。另外，阿斯利康公布的度伐利尤单抗ADRIATIC III期临床数据显示，度伐利尤单抗治疗在放疗后未出现进展的小细胞肺癌患者（SCLC）中，可以使患者的死亡风险降低27%。这些数据，意味着阿斯利康或许能够，进一步推动早期肺癌治疗的变革。除此之外，阿斯利康还在会上报告了DESTINY-Breast 06 III期研究的数据，显示Enhertu（DS-8201）对于HER2低表达、HER2超低表达的HR+乳腺癌患者同样具有卓越的疗效，这意味着Enhertu可以覆盖近90%的HR+乳腺癌患者，对于改变HER2表达的治疗范式具有重要意义。这些的亮眼的研究报告，让辉瑞、阿斯利康的股价连日上涨。 2 中国力量加速涌入 ASCO也见证了我国创新药的崛起。 2015年仅1项研究入选口头报告，今年超过50项，屡创新高；从ADC的全面崛起，到双抗、CAR-T的强势进击，以及多款全球首创或有潜力成为同类最佳的药物，越来越多的实力派中国创新药频频亮相。这也足以说明中国药企已经深度参与到全球的药物创新竞赛和市场竞争当中。今年ASCO的“人气王”无疑非ADC莫属。事实上，在几个月前的美国癌症研究协会上，关于ADC药物的相关研究壁报就已经被围得里三层外三层，ASCO则延续了之前的热度。来自中国的ADC研究，同样倍受关注。科伦博泰Trop2 ADC新药SKB264两项临床研究的数据，入选口头报告。2023年ASCO会议披露的首批人体临床研究数据，让外媒评论默沙东BD的操作“值麻了”。今年ASCO会议上，默沙东和科伦博泰公布了SKB264联合KL-A167一线治疗晚期NSCLC的II期研究结果。经过为期14个月的中位随访后，客观缓解率（ORR）为48.6%（18/37，2例待确认），疾病控制率（DCR）为94.6%，中位PFS为15.4个月。此次科伦博泰还公布了SKB264用于治疗局部复发性或转移性三阴乳腺癌三期临床最新数据。数据显示，相比化疗，接受SKB264三阴性乳腺癌治疗的疾病进展或死亡风险降低了69%，安全性可控。和SKB264竞争的同靶点同适应症产品有已经上市的吉利德Trodelvy，以及第一三共的DS1602。而从疗效数据上看，科伦博泰并不具有明显优势。荣昌生物则携带HER2 ADC RC48的多项研究亮相，向外界展示RC48在高风险非肌层浸润性膀胱癌、二线或复发/转移性宫颈癌，以及对标准治疗如顺铂化疗产生抵抗或无法耐受的晚期阴茎癌患者中的治疗潜力。尽管HER2领域竞争激烈，但差异化布局依然有脱颖而出的机会。而在HER2、TROP2这些热门靶点之外，ADC最前沿的研究领域，也已经开始出现中国企业的身影。比如，宜联生物与BioNTech合作开发的HER3 ADC YL-202，临床入组了EGFR突变非小细胞肺癌和HR+/HER2-乳腺癌。本次公布的I期临床数据显示，mPFS为6.0个月、9个月PFS比例为35.6%，mDOR为5.8个月，ORR为42.3%、DCR为94.2%。再比如，B7-H3 ADC。豪森生物公布了HS-20093的一期临床数据，共入组了56例广泛期小细胞肺癌患者，中位已接受2L治疗。有效性方面，在可评估疗效的52例患者中，8.0mpk与10.0mpk剂量组的ORR分别为58.1%和57.1%、DCR分别为80.6%和95.2%，8.0mpk组的mPFS为5.6个月、mDOR为4.3个月，10.0mpk的PFS和DOR尚不成熟。安全性方面，三级以上TRAE包括中性粒细胞减少、淋巴细胞减少、白细胞减少、血小板减少、贫血等典型的血液毒性。明慧医药则公布了B7-H3 ADC新药MHB088C的1/2期临床数据，共入组了60例实体瘤患者。在可评估疗效的12例患者中，出现5例PR，ORR为41.7%、DCR为91.7%；其中3例SCLC患者全部PR、都在第一次肿评即观察到。这些研究表明，国内药企正在极力向前冲刺，从血液瘤到实体瘤，从HER2到B7-H3、EGFR靶点等。尽管它们公布的数据相对早期，不确定性仍较高，但这依然告诉我们，在这个ADC大爆炸时代，机遇始终存在。 3 寻找掌声的方向不止ADC，在双抗、细胞疗法等领域，也不乏来自中国的创新力量在ASCO会议期间获得关注，大家都在努力奔向掌声的方向。只是，这个过程注定坎坷曲折。因为创新药研发，低垂的果子固然触手可及，但除了研发时间占优势，后续环节难度逐级递增，掌声更是无从谈起。要获得掌声，自然要比拼源头创新的实力。虽然九死一生，突围难度日益加码，但在出海征途下，也唯有此路，才能让我们持续推动潮水的方向。更何况，随着创新药领域低垂的果实被摘完，国内药企也不能永远停留在避风港，去挑战难度更高的创新药研发，是它们避不开也逃不掉的未来。尽管成功终究只是小概率游戏，节点也无法预知会在何时出现。但机会与希望永远存在。生物科技的本质，是新技术带来的指数增长机会，这种机会并不是时刻都有，但每次你觉得没创新的时候，很多创新都来了，掌声也随之而来。而在机会来临之前，不管是对投资者，还是创业者来说，都是极大的考验。这一点，不少药企在ASCO期间想必也深有体会。 ASCO不只有掌声，还有镰刀。对于参会者来说，每一次的大会披露临床数据，可能是天堂，但也可能是地狱，甚至你以为很好，市场却认为你不行。典型如康方生物，因在ASCO公布的AK112临床数据不及市场预期，股价一度暴跌近40%，市值蒸发187亿港元，人民币173.5亿元。在部分投资者眼中，相较于2期临床，3期临床HARMONi-A数据出现了“滑坡”：治疗效果变差了，毒副作用变大了。尽管这并不意味着AK112遭遇了实质挑战，但市场难免降低预期。而在以公司高管为首的乐观者看来，尽管数据下滑但并不影响AK112的竞争力，至少完胜信达生物的四联疗法。由于HARMONi-A数据存在的分歧，4个交易日内康方生物股价接近腰斩。尽管ASCO本质上还是一次学术会议，但会议期间创新药股价波动的现象也十分常见，这背后有基本面预期、催化、落地的因素以及市场关注度出现变动。事实上，在美股市场，因为ASCO会议上更新的数据不及预期，导致公司股价暴跌的现象并不罕见。比如，Verastem在发布核心产品的1/2期RAMP 205试验数据后，其股价应声暴跌66%。 Verastem的核心产品avutometinib和defactinib，将与吉西他滨和白蛋白结合型紫杉醇联合用于转移性胰腺导管腺癌（PDAC）的一线治疗。其中，avutometinib是一种RAF/MEK抑制剂，defactinib是一种口服选择性FAK抑制剂，两者联用，有望更全面地抑制癌细胞用来产生耐药性的信号通路。根据Verastem披露的数据，截至5月14日，在剂量水平为1的队列中，83%（5/6）的患者在数据截止时经过六个月以上的随访后获得了确认的部分缓解。在所有26名接受过扫描的患者中，21例目标病变有所减少。公司CEO John Hayslip称这一初步中期结果“令人鼓舞”，并“证明了靶向RAS/MAPK信号通路的重要性，因为90%以上的胰腺癌都有KRAS突变。”他们将继续进行研究，评估其他剂量和计划方案以确定2期推荐剂量。但是，二级市场并不买账。数据公布后，Verastem的股价已由11.88美元/股下跌至3.32美元/股，市值只有8400万美元。失意者也不止是biotehc的新研究。5月31日，吉利德在ASCO会议披露了Trodelvy在转移性NSCLC中的主要分析结果——III期研究EVOKE-01试验未达到主要终点，相比对照组多西他赛，Trodelvy对OS的改善未有统计差异性（11.1 vs 9.8个月）；中位PFS也只是略有改善（4.1 vs 3.9个月）。面对第一三共等发起的猛攻，Trodelvy正在失去光彩。但是，我们也应该正确看待这种挫折。创新很难被定义，当技术革新和新药物的涌现速度超出预期，这会促进整个领域的发展，也将加剧市场的竞争。因此，持续的研发投入和创新成为维持竞争优势的关键。这也是国内药企寻找掌声方向的关键。 — 总结 — 在国内甚至全球的行业寒潮中，市场情绪会不时低迷，但无论顺流、逆流，终究要向前游。回到ASCO来说，市场最关心的莫过于两点。一是新药研发进展，包括研究设计、临床试验进展、疗效和安全性等方面的信息；二是癌症治疗基础研究成果，包括新型治疗方法和手段等。而这次ASCO大会，似乎并未出现惊艳全场的新研究；从靶向治疗和免疫治疗的整体格局来说，整体上也未发生大的变化。但平静之下，涌动着变革的潜流，下一波药物创新的浪潮已在ADC、双抗、KRAS等阵地蓄势待发。在翻涌的浪潮中，我们更期待着中国创新力量的强势崛起，不仅仅是参与，而是深度塑造，让掌声为我们而响。这是时代的召唤，也是创新者不懈的追求。更多优质内容，欢迎关注↓↓↓

ASCO会议抗体药物偶联物临床结果临床1期

2024-06-12

·PRNewswire

Pancreatic Cancer on the Rise: How Biotech Firms are Developing Groundbreaking Treatments

USA News Group Commentary Issued on behalf of Oncolytics Biotech Inc. VANCOUVER, BC, June 12, 2024 /PRNewswire/ -- After looking at public health records for 3.8 million patients with invasive spreading cancer, researchers recently discovered that Generation X may be experiencing larger per-capita increases in the incidence of leading cancers, including the very deadly pancreatic cancer, compared to previous generations. The startling revelations come from a study conducted by experts at the National Cancer Institute's Division of Epidemiology and Genetics and was published in JAMA Network Open. Compared with baby boomers, Gen X women had projected increases in pancreatic, thyroid, kidney, rectal, uterine, colon, and ovarian cancers, as well as non-Hodgkin's lymphoma and leukemia. Among those, pancreatic cancer is generally considered the deadliest, with its very low five-year survival rate, typically late diagnosis, and aggressive nature. In order to significantly enhance patient health outcomes, several biotech developers are actively working on innovative solutions, including recent developments coming from O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), Verastem, Inc. (NASDAQ: VSTM), Candel Therapeutics, Inc. (NASDAQ: CADL), FibroGen, Inc. (NASDAQ: FGEN), and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN). Presented recently at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) presented two abstracts related to their novel immunotherapy, pelareorep, an intravenously delivered immunotherapeutic agent. One of the abstracts presented was a trial-in-progress for cohort 5 of the GOBLET study. This cohort will examine the effectiveness of combining pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with and without atezolizumab —made by Roche Holding AG (OTCQX: RHHBY)— in newly diagnosed patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The cohort is funded by a US$5 million Therapeutic Accelerator Award grant from the Pancreatic Cancer Action Network (PanCAN). Oncolytics Biotech expects to begin enrollment for this cohort this quarter, having received regulatory clearance to begin the enrollment process in May. "The first abstract outlines the design of a new GOBLET PDAC cohort that could significantly expand the potential of the company's pancreatic cancer program," said Dr. Matt Coffey, President and CEO of Oncolytics. "The chemotherapy regimens of mFOLFIRINOX and gemcitabine/nab-paclitaxel are the two most common standards of care in metastatic pancreatic cancer. We previously reported that the combination of pelareorep, gemcitabine, nab-paclitaxel, and atezolizumab yielded tumor response rates nearly triple historical results. Should the combination of pelareorep and mFOLFIRINOX produce a similarly positive outcome, an even broader range of metastatic PDAC patients may benefit from pelareorep-based therapy." The GOBLET cohort 5 abstract and poster outline a study evaluating new treatments for patients with newly diagnosed metastatic PDAC using a Simon two-stage design. This design helps determine if a treatment is promising enough to continue testing. In the first stage, 15 patients in each treatment arm will be randomly assigned to receive either pelareorep with mFOLFIRINOX or pelareorep with mFOLFIRINOX and atezolizumab. The main goals are to measure how well the treatments work and their safety. Additionally, the study will look at progression-free survival (how long patients live without the cancer getting worse), overall survival (how long patients live overall), and biomarkers (indicators of how the body responds to the treatment). If the first stage is successful, one or both groups may proceed to Stage 2, which will include 17 more patients per treatment arm. Blood and tumor samples will be collected for further analysis throughout the study. Also presented at ASCO's meeting were positive initial interim safety and efficacy results from Verastem, Inc. (NASDAQ: VSTM) in an ongoing Phase 1/2 trial evaluating its avutometinib plus defactinib in combination with gemcitabine and Nab-paclitaxel for first-line treatment in patients with metastatic pancreatic cancer. Like Oncolytics' pelareorep, Verastem's avutometinib received funding from PanCAN through its Therapeutic Accelerator Award. " Verastem was the inaugural recipient of the PanCAN Therapeutic Accelerator Award, which has been an important part of PanCAN's approach to advancing innovative treatments for pancreatic cancer," said Anna Berkenblit, M.D., MMSc, Chief Scientific and Medical Officer at PanCAN. "There is a critical need for new treatment options in this disease, and we hope that the results from this study lead to improved outcomes for patients with pancreatic cancer." As of May 14, 2024, Verastem reported that patients receiving the combination therapy achieved a confirmed overall response rate (ORR) of 83%, with 5 out of 6 patients responding positively. The release of these results led to a positive market reaction, boosting Verastem's shares in pre-market trading in the process. Notably, there was one case of dose-limiting toxicity (febrile neutropenia) in the dose level 1 cohort. However, this dose level was cleared after enrolling additional patients in three other cohorts of the study. "The initial interim results from the RAMP 205 trial evaluating avutometinib and defactinib in combination with standard of care first-line chemotherapy are encouraging and demonstrate the importance of targeting the RAS/MAPK pathway, as more than 90% of pancreatic tumors have a KRAS mutation," said John Hayslip, M.D., Chief Medical Officer of Verastem Oncology. "We continue to progress the study evaluating other dose and schedule regimens to determine the recommended Phase 2 dose in the trial." In another recent update, Candel Therapeutics, Inc. (NASDAQ: CADL) reported "very encouraging results" from its phase 2 clinical trial of CAN-2409, which targets borderline resectable pancreatic cancer. The data showed that patients treated with CAN-2409 had an estimated median overall survival of 28.8 months, compared to just 12.5 months for the control group. Furthermore, at 24 months, the survival rate was 71.4% for those treated with CAN-2409, whereas the control group had a survival rate of only 16.7% following chemoradiation. "Given the frequent recurrence and short survival with SoC chemotherapy for non-metastatic PDAC, effective new treatment options are urgently needed," said Garrett Nichols, MD, MS, Chief Medical Officer of Candel. "We are very encouraged by the improved survival associated with CAN-2409, which has been shown to be durable after prolonged follow-up based on the updated data in this randomized clinical trial. CAN-2409 was generally well tolerated without significant additional local or systemic toxicity when added to SoC chemoradiation." Because pancreatic cancer is considered a solid tumor, news of a joint effort between FibroGen, Inc. (NASDAQ: FGEN) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announcing a supply agreement to evaluate FG-3165 as a monotherapy and in combination with LIBTAYO in patients with select solid tumors is relevant. Under the clinical study collaboration and supply agreement, Regeneron will provide drug supply to FibroGen, who will be the sponsor of each Phase 1 monotherapy and combination trial. Each company retains all rights to their respective compounds, including as a monotherapy or as combination therapies. "We are very excited to collaborate with Regeneron Pharmaceuticals to evaluate two separate novel combination approaches to treat patients with select solid tumors," said Deyaa Adib, M.D., Chief Medical Officer of FibroGen. "We believe that the mechanisms of action for both FG-3165 (anti-Gal9) and FG-3175 (anti-CCR8) have the potential to be synergistic with cemiplimab, providing the possibility for an improvement in clinical outcomes for patients. We look forward to building a collaborative relationship with Regeneron, who is a leader in oncology therapeutic products development and commercialization." In their Q1 2024 financial results, FibroGen announced several upcoming milestones. The company expects to release topline data from the PanCAN Precision Promise Phase 2/3 study of pamrevlumab in metastatic pancreatic cancer by mid-2024. Additionally, they anticipate delivering topline data from the LAPIS Phase 3 study of pamrevlumab in locally advanced unresectable pancreatic cancer (LAPC) in Q3 2024. "Looking ahead, we expect to report topline data from our two late-stage clinical trials of pamrevlumab in pancreatic cancer in the coming months," said Thane Wettig, CEO of FibroGen. Article Source: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCE USA News Group

临床结果临床1期临床2期ASCO会议免疫疗法

100 项与 Defactinib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10618	-	-	DB12282

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
卵巢浆液性肿瘤	申请上市	美国	Verastem, Inc.	2024-05-24
脑转移瘤	临床2期	美国	Verastem, Inc.	2024-02-08
胰腺继发性恶性肿瘤	临床2期	美国	Verastem, Inc.	2023-03-22
中肾瘤	临床2期	美国	Verastem, Inc.	2023-03-15
子宫内膜癌	临床2期	美国	Verastem, Inc.	2023-02-06
卵巢黏液性腺癌	临床2期	美国	Verastem, Inc.	2023-02-06
宫颈癌	临床2期	美国	Verastem, Inc.	2023-02-06
KRAS G12C突变非小细胞肺癌	临床2期	美国	Verastem, Inc.	2022-04-12
KRAS G12C突变非小细胞肺癌	临床2期	比利时	Verastem, Inc.	2022-04-12
KRAS G12C突变非小细胞肺癌	临床2期	法国	Verastem, Inc.	2022-04-12

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临床结果

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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, 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	觸範蓋觸窪範願艱鑰襯(窪製壓鹹衊選繭夢選襯) = 遞窪鏇壓鹹鏇齋窪選膚顧壓夢膚淵築夢獵選積 (遞範餘鏇遞鹹簾齋糧蓋 ) 更多	积极	2024-05-24
NCT02004028 (CTgov)	临床2期	恶性胸膜间皮瘤	35	Defactinib (Cohort 1)	窪遞夢積淵憲顧網觸網(餘鬱淵獵糧夢衊繭憲觸) = 觸糧鏇鹽鬱範遞膚憲顧衊顧鏇鹽廠齋廠積鹽襯 (蓋壓衊構鬱選繭窪襯窪, 窪淵鬱鑰觸艱網築憲觸 ~ 餘繭淵製窪範製範觸積) 更多	-	2024-02-20
				Defactinib (Cohort 2)	窪遞夢積淵憲顧網觸網(餘鬱淵獵糧夢衊繭憲觸) = 鏇顧製憲糧築鹹網壓鹽衊顧鏇鹽廠齋廠積鹽襯 (蓋壓衊構鬱選繭窪襯窪, 構艱夢蓋範艱範築衊齋 ~ 選夢襯繭衊獵網範糧簾) 更多
NCT03727880 (ASCO2023) 人工标引	临床2期	胰腺导管腺癌新辅助 \| 辅助	-	Pembrolizumab+Defactinib	網襯觸觸網構簾築蓋齋(膚範繭構淵鏇憲簾鏇鏇) = 膚壓簾範範憲窪齋齋顧壓鬱淵願襯觸構鑰製餘 (範鬱廠獵齋鏇壓繭夢範 ) 更多	积极	2023-05-31
				Pembrolizumab	網襯觸觸網構簾築蓋齋(膚範繭構淵鏇憲簾鏇鏇) = 獵淵壓繭襯鏇窪鏇網選壓鬱淵願襯觸構鑰製餘 (範鬱廠獵齋鏇壓繭夢範 ) 更多
NCT04620330 (RAMP 202, ASCO2023) 人工标引	临床2期	KRAS突变非小细胞肺癌 KRAS G12V Mutantion	35	Avutometinib	艱窪壓蓋遞願範廠鬱鹹(網壓獵鏇衊範廠範積衊) = 餘觸蓋鏇艱網衊鏇鹽膚廠選築繭壓憲鑰膚觸網 (範齋顧獵齋鹽夢範鏇蓋 )	不佳	2023-05-26
				Defactinib+Avutometinib	艱窪壓蓋遞願範廠鬱鹹(網壓獵鏇衊範廠範積衊) = 鏇憲鹹範衊艱積窪鹹憲廠選築繭壓憲鑰膚觸網 (範齋顧獵齋鹽夢範鏇蓋 )
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)	糧鏇觸鏇顧膚網衊壓鑰(製網夢鑰鏇憲夢鹹醖壓) = 製淵構壓夢窪鑰餘糧廠廠淵願淵願鑰齋憲簾蓋 (膚構窪顧衊鑰窪艱窪繭 ) 更多	不佳	2022-10-04
				VS-6766+defactinib (non-G12V KRAS mutations)	糧鏇觸鏇顧膚網衊壓鑰(製網夢鑰鏇憲夢鹹醖壓) = 構構獵獵繭鬱憲糧顧遞廠淵願淵願鑰齋憲簾蓋 (膚構窪顧衊鑰窪艱窪繭 ) 更多
NCT02546531 (ASCO2022) 人工标引	临床1期	胰腺癌	-	Defactinib+Pembrolizumab+gemcitabine (PDAC)	簾壓廠鏇獵築齋齋糧齋(壓網壓蓋淵衊獵鑰齋餘) = 構製壓艱壓遞願顧衊鏇衊觸範鏇鏇憲衊願淵鹽 (鏇蓋艱蓋網範網簾餘簾 ) 更多	积极	2022-06-02
				Defactinib+Pembrolizumab+gemcitabine (PDAC in maintenance cohort)	簾壓廠鏇獵築齋齋糧齋(壓網壓蓋淵衊獵鑰齋餘) = 鹹繭廠願廠鑰鹽艱繭選衊觸範鏇鏇憲衊願淵鹽 (鏇蓋艱蓋網範網簾餘簾 ) 更多
NCT03875820 (ESMO2021) 人工标引	临床1期	卵巢癌	25	VS-6766+defactinib	範顧襯醖襯範積遞衊範(獵餘觸夢鏇繭鹹襯構鬱) = 獵衊餘窪構衊鏇齋構願鹽膚選願築蓋艱鹽窪蓋 (鏇餘壓窪糧願膚艱網醖 ) 更多	积极	2021-09-19
				VS-6766+defactinib (pts with KRAS mutations)	範觸鹽艱簾餘齋構觸膚(艱選糧夢鬱衊鹽鑰簾醖) = 齋衊蓋淵醖壓網構範鬱廠醖構膚蓋築襯繭壓醖 (構夢餘鏇鏇製繭淵選觸, 35 ~ 85)
NCT04439331 (MATCH, ASCO2021) 人工标引	临床2期	2型神经纤维瘤病 NF2 Deletion	35	defactinib	夢繭製網蓋廠製憲獵積(廠餘夢獵淵膚壓艱鬱糧) = 餘構繭壓齋衊鹽鬱觸鹹鏇蓋範構網網遞製鑰衊 (艱窪遞鏇顧鏇遞願淵鑰, 0.16 ~ 14.86) 更多	不佳	2021-05-28
AACR2021 人工标引	临床1期	KRAS突变肿瘤 KRAS G12V Mutation	19	VS-6766 3.2-4 mg+defactinib 200 mg	壓積觸齋齋憲顧蓋醖餘(鹹窪獵衊選鑰觸糧積膚) = 獵廠鑰憲鑰顧夢壓網鬱願積蓋願糧淵壓衊艱窪 (獵鹹憲繭窪襯鹹鑰願壓 ) 更多	积极	2021-04-10
NCT03875820 (AACR2020)	临床1期	KRAS 突变结直肠癌	87	CH5126766/VS-6766	窪積齋夢廠餘糧選積夢(衊鬱壓範鏇憲醖艱齋選) = 選壓糧淵憲窪選衊選範膚壓壓餘憲鹽範蓋襯鹽 (憲構蓋鹹製遞選膚廠顧 )	积极	2020-08-15
				Defactinib	窪積齋夢廠餘糧選積夢(衊鬱壓範鏇憲醖艱齋選) = 獵鹹鑰積鏇遞襯餘鬱窪膚壓壓餘憲鹽範蓋襯鹽 (憲構蓋鹹製遞選膚廠顧 )