Gemfibrozil

整理：肿瘤资讯 来源：肿瘤资讯 2026年美国癌症研究协会（AACR）年会于4月17至22日举行。作为全球规模最大的肿瘤学研究盛会之一，AACR汇聚了来自世界各地的顶级科学家、临床医生及创新药研发者，共同探讨从基础研究到临床转化的最新突破。目前大会官网已公布摘要内容，【肿瘤资讯】特此整理了本届大会中胰腺癌领域的多项重磅口头报告内容，以飨诸君。 Daraxonrasib联合化疗一线治疗转移性PDAC患者 摘要号：LB407 / 7 英文标题：Daraxonrasib plus chemotherapy (CT) as first-line (1L) treatment for patients (Pts) with metastatic pancreatic adenocarcinoma (mPDAC). 中文标题：Daraxonrasib联合化疗一线治疗转移性胰腺癌（mPDAC） 汇报者：Brian Wolpin（丹娜-法伯癌症研究所） 研究背景 转移性胰腺癌（mPDAC）是一种具有挑战性的RAS驱动性疾病。标准一线化疗获益有限[客观缓解率（ORR）：23%~43%；6个月无进展生存率（PFS）：40%~50%；中位总生存期（OS）：8.5~11.7个月]。致癌性RAS突变发生于超过90%的PDAC患者。Daraxonrasib是一种强效口服RAS(ON)多选择性抑制剂，靶向GTP结合的突变型（包括G12、G13和Q61突变）及野生型RAS。一项针对二线mPDAC患者的I/II期研究（NCT05379985）显示，daraxonrasib具有可控的安全性和早期疗效。在临床前PDAC模型中，daraxonrasib联合化疗提高了缓解深度和持久性。本研究（NCT06445062）中，一线患者接受daraxonrasib联合吉西他滨/白蛋白结合型紫杉醇（GnP）治疗，该方案旨在通过维持足量的daraxonrasib剂量强度持续抑制RAS信号通路，并安全利用化疗的抗肿瘤活性。 研究方法 RAS突变mPDAC一线患者接受daraxonrasib（200 mg每日一次）联合GnP（第1、15天给药）治疗。评估安全性、耐受性、药代动力学（PK）、抗肿瘤活性及循环肿瘤DNA（ctDNA）应答。 研究结果 截至2025年12月1日，40例mPDAC患者接受了daraxonrasib联合GnP治疗（中位随访时间9.7个月）。联合方案的安全性特征与各组分已知毒性一致。全级别治疗相关不良事件（TRAE）（发生率≥30%）包括皮疹（90%）、腹泻（75%）、疲劳（70%）、恶心（68%）、呕吐（55%）、贫血（50%）、口腔炎/黏膜炎（45%）、外周水肿（43%）、中性粒细胞计数降低（43%）、血小板计数降低（38%）、外周感觉神经病变（38%）、脱发（33%）及天门冬氨酸氨基转移酶升高（30%）。≥3级TRAE（发生率≥10%）包括贫血（33%）、中性粒细胞计数降低（20%）、疲劳（18%）、皮疹（15%）、腹泻（15%）及口腔炎/黏膜炎（10%）。未发生5级TRAE。daraxonrasib的平均剂量强度为82%，GnP为80%。初步疗效数据显示，在40例治疗患者中，客观缓解率（ORR）为58%（95% CI: 41%~73%），疾病控制率（DCR）为90%（95% CI: 76%~97%），6个月无进展生存率（PFS）为84%（95% CI: 68%~93%）；在39例可评估患者中，ORR为59%（95% CI: 42%~74%），DCR为92%（95% CI: 79%~98%）。ctDNA应答方面，28例基线及至少一次治疗中测序的患者中，RAS变异等位基因频率（VAF）降低超过50%者占96%，VAF完全清除者占61%。 研究结论 Daraxonrasib联合GnP显示出可控的安全性及令人瞩目的初步疗效，支持在mPDAC一线治疗中启动一项全球三臂III期研究（RASolute 303），比较daraxonrasib单药、daraxonrasib联合GnP与GnP单药的疗效。 LOKON001研究：LOAd703联合白蛋白紫杉醇、吉西他滨和阿替利珠单抗治疗晚期胰腺癌的I/II期试验 摘要号：CT031 英文标题：A phase I/II trial evaluating LOAd703 in combination with nab-paclitaxel, gemcitabine, and atezolizumab for advanced pancreatic cancer 中文标题：一项评估LOAd703联合白蛋白结合型紫杉醇、吉西他滨和阿替利珠单抗治疗晚期胰腺癌的I/II期试验 汇报者：Angelica Loskog[瑞典乌普萨拉（Uppsala）大学] 研究背景 LOAd703是一种对肿瘤微环境（TME）进行基因工程改造、具有肿瘤选择性的溶瘤腺病毒。该病毒编码三聚体、膜结合型CD40L和4-1BBL，旨在诱导体内Th1型肿瘤反应性细胞毒性T细胞的扩增。在LOKON001研究的第1臂中，瘤内注射LOAd703联合静脉（IV）白蛋白结合型紫杉醇及吉西他滨（nPG）方案已被证实对晚期胰腺癌（PC）患者是安全的，并能成功重编程TME及诱导肿瘤反应性T细胞扩增。 研究方法 在LOKON001研究的第2臂中（初步数据报告），24名晚期PC患者（III期，n=2；IV期，n=22）接受了最多12次每两周一次的LOAd703瘤内注射［1x1011 VP（n=12）或5x1011 VP（n=12）］、标准nPG方案（白蛋白结合型紫杉醇125 mg/m²联合吉西他滨1000 mg/m²，于28天周期的第1、8、15天IV给药）以及PD-L1抑制剂阿替利珠单抗（1680mg，于每个28天nPG周期的第1天IV给药）。主要终点是安全性和可行性。 研究结果 入组患者的中位年龄为60岁（IQR：53~65），46%的患者曾接受过针对晚期PC的系统治疗。患者接受了中位7次（IQR：5~10）LOAd703注射、6次（IQR：4~9）阿替利珠单抗输注，并开始了中位7个（IQR：4~9）化疗周期。治疗耐受性良好，与LOAd703相关的最常见1~2级不良事件为发热（67%）、寒战（46%）、疲劳（25%）、头痛（21%）和低血压（17%）。报告了8起可能与LOAd703和阿替利珠单抗均相关的3/4级事件，其中3起为肾脏毒性（1例患者出现3级和4级急性肾损伤，第2例患者出现3级膜增生性肾小球肾炎）。其余3/4级不良事件归因于基础疾病、化疗、阿替利珠单抗或其他原因。在可评估患者（n=24）中，客观缓解率（ORR）和疾病控制率（DCR）分别为29%（95%CI：15~49）和88%（95%CI：69~96）。在一线（1L）治疗患者中，ORR和DCR分别为38%（95%CI：18~65）和85%（95%CI：58~97）。3名患者（均为1L治疗）获得完全缓解（CR），总体CR率为13%（1L治疗患者为23%）。所有可评估患者的中位总生存期（OS）为9个月（95%CI：7~14），1L治疗患者为15.5个月（95%CI：7~24）。肿瘤mRNA谱分析显示，适应性免疫应答生物标志物上调，并确定了与治疗反应及生存相关的特征。 研究结论 LOAd703联合nPG和阿替利珠单抗具有安全性，可诱导有利的适应性免疫特征，并显示出令人鼓舞的抗肿瘤活性，值得在随机临床试验中进一步开展研究。 ACCENT研究：FAK抑制剂联合化疗一线治疗晚期胰腺癌中期分析 摘要号：CT304 英文标题：Narmafotinib (AMP945) in combination with gemcitabine and nab-paclitaxel in first-line patients with advanced pancreatic cancer (ACCENT trial) a Phase 1b 2a study-Interim analysis 中文标题：Narmafotinib（AMP945）联合吉西他滨和白蛋白结合型紫杉醇用于晚期胰腺癌一线患者（ACCENT试验）：一项Ib/IIa期研究的中期分析 汇报者：T.-A. Cock（澳大利亚，墨尔本） 研究背景 Narmafotinib（AMP945）是一种高效且选择性的黏着斑激酶（FAK）抑制剂。FAK是一种在胰腺癌（PCa）中过度表达的非受体酪氨酸激酶，在肿瘤微环境中促进细胞存活、增殖、迁移、化疗耐药以及潜在的纤维化和免疫抑制。ACCENT（NCT05355298）是一项评估Narmafotinib联合吉西他滨/白蛋白结合型紫杉醇（Gem/NabP）治疗转移性PCa患者的Ib/IIa期（PIb/IIa）试验。PIb期剂量递增已完成，确定400mg的Narmafotinib为推荐的PIIa期剂量。PIIa期研究在澳大利亚和韩国进行，中期结果报告如下。 研究方法 ACCENT试验是一项开放标签、由两部分组成的研究，旨在评估Narmafotinib联合标准Gem/NabP作为转移性PCa患者一线治疗的药代动力学（PK）、安全性和耐受性以及疗效。在传统的28天周期的第1、8和15天给予Gem（1000mg/m2）和NabP（125mg/m2）。患者还在第1周期的第-8天至第-2天每天接受Narmafotinib（400mg，口服）治疗，然后从每个28天化疗周期的第3、10和24天开始以4天脉冲方式联合给药。主要终点是研究者根据RECIST 1.1标准评估的客观缓解率（ORR）。关键次要终点包括不良事件（AEs，使用NCI CTCAEv5.0标准）、无进展生存期（PFS）和总生存期（OS）。 研究结果 接受400mg的Narmafotinib治疗的ACCENT患者（PIb/IIa期，N=64）：ECOG评分为0~1分；中位年龄为62.7岁；男性占50%。截至2026年1月20日，ORR为42%（在可评估患者中确认为38%），包括1例完全缓解和1例后来被确定为病理学完全缓解的部分缓解。许多患者的结果显示肿瘤体积大幅缩小且在治疗期间持续存在，21%的可评估患者接受治疗超过12个月，包括2例目前在研究中分别达到21个月和18个月仍在继续治疗的患者。这些临床获益转化为中位OS改善至11.1个月，中位缓解持续时间改善至6.9个月，中位PFS改善至7.7个月；这些结果优于单独化疗的MPACT基准研究（OS为8.5个月，DoR为5个月，PFS为5.5个月）。与Narmafotinib相关的最常见AE为恶心（29%）、腹泻（16%）、呕吐（15%）、疲劳（11%）、胃食管反流（7%）和便秘（6%），严重程度主要为1~2级。毒性与既往报道的单独化疗毒性相似。 研究结论 Narmafotinib联合Gem/NabP达到了其主要疗效终点，同时对化疗的整体安全性和耐受性影响有限。鉴于Narmafotinib在本研究中是间歇给药（每个周期12/28天），并注意到其良好的安全性和耐受性，包括关键试验在内的后续研究将采用每日给药的方式，这可能会进一步提高疗效。 排版编辑：as 版权声明 本文专供医学专业人士参考，未经著作人许可，不可出版发行。同时，欢迎个人转发分享，其他任何媒体、网站如需转载或引用本网版权所有内容，须获得授权，且在醒目位置处注明"转自：良医汇-肿瘤医生APP"。

PARAMUS, N.J., April 21, 2026 (GLOBE NEWSWIRE) -- Polaryx Therapeutics, Inc. (Nasdaq: PLYX), a clinical-stage biotechnology company developing disease-modifying therapies for rare pediatric LSDs, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to PLX-200 for the treatment of Juvenile Neuronal Ceroid Lipofuscinosis (JNCL/CLN3 disease), Krabbe disease (globoid cell leukodystrophy), and Sandhoff disease (GM2 gangliosidosis Type II). Following the March 2026 grant of FTD to PLX-200 in treatment of Late-Infantile Neuronal Ceroid Lipofuscinosis (LINCL/CLN2 disease), PLX-200 now holds FTD for all four prospective indications to be studied in the SOTERIA Phase 2 basket trial. The Fast Track program is designed to facilitate and expedite the review of therapies intended to treat serious or life-threatening conditions with unmet medical need. Companies receiving Fast Track Designation may benefit from more frequent interactions with the FDA and the potential for rolling review of a future marketing application. “We are delighted by the FDA’s decision to further extend Fast Track Designation to CLN3, Krabbe disease, and Sandhoff disease,” said Alex Yang, Chair and Chief Executive Officer of Polaryx Therapeutics. “As we prepare to advance the SOTERIA Phase 2 basket trial, receiving this designation across all four indications underscores the enormous need that exists in the current LSD landscape while also recognizing PLX-200’s potential to meaningfully address treatment gaps across multiple LSDs.” “CLN2 disease, CLN3 disease, Krabbe disease, and Sandhoff disease are devastating neurodegenerative conditions with limited or no disease‑modifying treatment options. The regulatory alignment received from the FDA’s Fast Track Designations highlight the seriousness of these disorders and the need for new therapeutic options like PLX-200,” said Lisa L. Bollinger, M.D., Chief Medical Officer of Polaryx Therapeutics. “We remain focused on preparing the SOTERIA trial to advance PLX‑200 into the clinic in the second half of 2026.” About PLX-200 Polaryx’s lead drug candidate, PLX-200, is an orally available compound comprised of gemfibrozil. Gemfibrozil is an FDA-approved lipid regulating agent in the fibrate family which has only been approved in a capsule form for adult patients with very high elevations of serum triglyceride levels to decrease serum triglycerides and very low-density lipoprotein cholesterol and increase high density lipoprotein cholesterol. The ability of gemfibrozil to cross the blood-brain barrier (BBB) has also been documented in third-party preclinical trials and safe use of gemfibrozil in adults has also been well-established over several decades of clinical investigation and commercial use, which we believe accelerates clinical development and reduces associated costs. We believe the unique ability of PLX-200 to cross the BBB, along with its widely applicable mechanism of action, positions PLX-200 to potentially address the immense unmet need in multiple rare, catastrophic LSD indications. About the SOTERIA Trial SOTERIA is a Phase 2, open-label, single arm trial intended to assess the safety, tolerability, and clinical activity of Polaryx’s lead drug candidate, PLX-200, in CLN2, CLN3, Krabbe disease, and Sandhoff disease, four different LSDs whose patient populations Polaryx believes represent approximately one quarter of the LSD population. SOTERIA is designed to be flexible, resource-efficient, and provide important data and information important to PLX-200’s future clinical development. Polaryx received a safe to proceed letter in October 2025 from the FDA and plans to initiate SOTERIA in the second half of 2026 in trial sites in the United States as well as in Europe and Asia or other foreign jurisdictions. Designed with a high degree of flexibility, SOTERIA represents a resource-efficient opportunity to validate PLX-200’s preclinical science across multiple LSDs while gathering data that will be invaluable in planning PLX-200’s future development pathway, including the initiation of potentially pivotal trials. For the CLN2 and CLN3 cohorts, although the entire trial is open label, these cohorts will incorporate analyses comparing natural history data as a control arm to PLX-200’s treated arm. A natural history study is a preplanned observational study intended to track the course of the disease. Should the data demonstrate compelling clinical activity, Polaryx may seek conditional marketing authorization. About CLN3 Disease CLN3 disease, also known as juvenile neuronal ceroid lipofuscinosis (JNCL) or juvenile Batten disease, is a rare inherited LSD that primarily affects the nervous system in childhood. With a prevalence of one in 100,000 births worldwide, CLN3 disease is caused by mutations in the CLN3 gene which encodes a lysosomal transmembrane protein, Battenin. The most common genetic defect is a ~1-kb deletion in CLN3, leading to a loss of protein function. The disorder follows an autosomal recessive inheritance pattern, requiring two defective copies of CLN3 for disease manifestation. Due to impaired lysosomal function, neurons accumulate waste material and progressively deteriorate, resulting in a neurodegenerative disease course. About Krabbe Disease Krabbe disease, also known as globoid cell leukodystrophy, is caused by mutations in the galactosylceramidase (GALC) gene, leading to GALC deficiency and an inability to break down certain lipids in the body. This results in accumulation of toxic substances in the brain and other areas of the nervous system leading to demyelination and severe neurological decline. The incidence rate of Krabbe disease varies significantly, affecting 0.3 to 2.6 per 100,000 live births. We believe that there are approximately 6,700 Krabbe disease patients in the United States, Europe and select regions of the ROW. Hematopoietic stem cell transplantation (HSCT) is considered the current standard of care. About Sandhoff Disease Sandhoff disease, a more severe form of Tay-Sachs disease, is caused by mutations in the HEXB gene, which impair the function of β-hexosaminidase enzymes. This deficiency causes the accumulation of GM2 gangliosides in neurons, resulting in progressive neurodegeneration. Several subtypes of Sandhoff disease exist, varying depending on the age of onset. The infantile form typically manifests between three and six months of age and is the most severe. The first symptom is often hypotonia, accompanied by an exaggerated startle response to auditory stimuli, followed by developmental regression. Acute infantile and sub-acute juvenile Sandhoff disease patients begin regressing significantly after the onset of symptoms, with death usually occurring between two and three years for the infantile cohort and early to late teens for the juvenile cohort. Life expectancy for late-onset Sandhoff patients is not significantly impacted. We believe that there are approximately 1,200 Sandhoff disease patients in the United States, Europe and select regions of the ROW. Forward-Looking Statements Certain statements in this press release may constitute “forward-looking statements” within the meaning of the federal securities laws, including, but not limited to, statements regarding: Polaryx’s clinical development plans for PLX-200, including the timing for initiation of the SOTERIA trial. Words such as “may,” “might,” “will,” “objective,” “intend,” “should,” “could,” “can,” “would,” “expect,” “believe,” “design,” “estimate,” “predict,” “potential,” “develop,” “plan” or the negative of these terms, and similar expressions, or statements regarding intent, belief, or current expectations, are forward-looking statements. While Polaryx believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties (including, without limitation, those set forth in Polaryx’s filings with the U.S. Securities and Exchange Commission (the SEC), many of which are beyond the company’s control and subject to change. Actual results could be materially different. Risks and uncertainties include: global macroeconomic conditions and related volatility, expectations regarding the initiation, progress, and expected results of Polaryx’s clinical trials; expectations regarding the timing, completion and outcome of Polaryx’s clinical trials; the timing or likelihood of regulatory filings and approvals; liquidity and capital resources; and other risks and uncertainties identified in Polaryx’s most recently filed Form 10-K with the SEC and subsequent disclosure documents Polaryx may the SEC. Polaryx claims the protection of the Safe Harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. Polaryx expressly disclaims any obligation to update or alter any statements whether as a result of new information, future events or otherwise, except as required by law. Media Contact: CORE IR (212) 655-0924 media@polaryx.com Investor Contact: CORE IR (212) 655-0924 investor@polaryx.com