Azacitidine

Feedback from U.S. FDA supports advancement into Phase 2 STRIDE-MDS trial in patients with R/R HR-MDS First-in-class, mutation-agnostic approach has the potential to address a broad R/R HR-MDS population PureTech intends to secure external capital in the first half of 2027 to support the continued development of LYT-200 through its Founded Entity, Gallop Oncology PureTech Health plc (LSE: PRTC) ("PureTech" or the "Company"), a hub-and-spoke biotherapeutics company dedicated to giving life to science and transforming innovation into value, today announced the successful completion of the End-of-Phase 1 (EOP1) meeting with the U.S. Food and Drug Administration (FDA) and the receipt of FDA Fast Track designation for LYT-200 in combination with a hypomethylating agent (HMA) for the treatment of relapsed/refractory (R/R) high-risk myelodysplastic syndromes (HR-MDS). LYT-200 targets galectin-9, an important oncogenic driver and potent immunosuppressor, and is being advanced by PureTech’s Founded Entity, Gallop Oncology (Gallop). PureTech intends to leverage external capital to support the continued development of LYT-200 through the completion of the Phase 2 trial and expects to secure capital in the first half of 2027. “Our productive End-of-Phase 1 meeting with the U.S. FDA provides a clear path to advance LYT-200 into Phase 2 development,” said Eric Elenko, PhD, Acting Chief Executive Officer of Gallop Oncology and Co-founder of PureTech. “The STRIDE-MDS trial will seek to confirm the unprecedented clinical activity observed in Phase 1b, while its randomized, double-blind design will enable a clear assessment of the contribution of effect of LYT-200. Additionally, the inclusion of two doses is intended to fulfill the dose-selection requirements in accordance with FDA’s Project Optimus. With its mutation-agnostic approach and potential to benefit a broad range of patients, LYT-200 could represent an important new treatment option for R/R HR- MDS.” The Study of Two Regimens Investigating Dose and Efficacy of LYT‑200 in Relapsed/Refractory High-Risk MDS (STRIDE-MDS) will be a randomized, double-blind, placebo-controlled Phase 2 trial enrolling approximately 125 patients with R/R HR-MDS. Patients will be randomized 2:2:1 to receive LYT-200 at 12 mg/kg plus an HMA, LYT-200 at 7.5 mg/kg plus an HMA, or placebo plus an HMA, respectively. The trial will assess the efficacy of LYT-200 as measured by the rate of complete and partial responses to support dose selection. “R/R HR-MDS remains an area of profound unmet need, particularly for the vast majority of patients without an actionable mutation,” said Aleksandra Filipovic, MD, PhD, Chief Medical Officer of Gallop Oncology. “Galectin-9 represents a compelling therapeutic target because of its role as both an oncogenic driver and potent immunosuppressor, and its elevated expression in HR-MDS is associated with shorter survival. By addressing the foundational biology – independent of a specific genetic mutation – LYT-200 has the potential to offer a new approach for a broad population of patients, and we welcome the opportunity Fast Track designation provides to work more closely with the U.S. FDA as we advance its development.” The EOP1 meeting was supported by positive topline data from the completed Phase 1b trial evaluating LYT-200 in combination with an HMA (azacitidine or decitabine) in heavily pretreated patients with R/R HR-MDS. In that trial, LYT-200 demonstrated compelling clinical efficacy and a consistent safety profile in patients with R/R HR-MDS, all of whom had relapsed or become refractory to prior treatment with an HMA. Efficacy evaluable1 patients receiving LYT-200 (12 mg/kg) in combination with an HMA (n=11) demonstrated: 27.3% complete response rate 36.3% complete response + partial response rate 9.1% partial response rate 9.1% marrow complete response rate 45.5% overall response rate 18% conversion to transplant rate No dose-limiting toxicities No myeloid suppression “Patients with higher-risk MDS who relapse or become refractory to HMA treatment have very limited therapeutic options and poor outcomes, and the literature and clinical practice suggest that fewer than 5% of these patients typically respond to retreatment with an HMA rechallenge,” said Amer Zeidan, MBBS, MHS, Professor of Medicine at Yale University, Chief of the Division of Hematologic Malignancies at Yale Cancer Center, who will be the Global Principal Investigator of the Phase 2 STRIDE-MDS trial. “Against this backdrop, the clinical activity observed with LYT-200 in combination with an HMA in the Phase 1b study is particularly encouraging. STRIDE-MDS will allow us to further evaluate this activity in a randomized, placebo-controlled study.” Fast Track designation is a process designed to facilitate the development and expedite the review of drugs that target serious conditions with unmet medical need. Drugs receiving Fast Track designation may benefit from more frequent interactions with the U.S. FDA throughout development. Myelodysplastic syndromes (MDS) are a group of serious blood cancers characterized by ineffective blood cell production in the bone marrow, leading to anemia, infections, and bleeding complications.2, 3 MDS affects approximately 60,000-170,000 people in the United States, with an estimated 30-40% of patients diagnosed with the more aggressive form of the disease known as high-risk (HR) MDS.2, 4 HR-MDS is associated with poor outcomes, with median survival typically less than two years following diagnosis. The current standard frontline treatments for HR-MDS are hypomethylating agents (HMAs), such as azacitidine and decitabine; however, most patients do not respond to these therapies or eventually stop benefiting from them.5 Once the disease becomes relapsed or refractory (R/R), outcomes are especially poor, with survival often limited to only a few months.5,6 Treatment options for patients with R/R HR-MDS remain very limited. Only one therapy has been approved by the U.S. Food and Drug Administration specifically for R/R HR-MDS in the past two decades, and it targets a genetic mutation found in only approximately 3% of patients.5 As a result, there remains a significant unmet need for treatments for the overwhelming majority of patients with R/R HR-MDS. LYT-200 is a Phase 2-ready, fully human monoclonal antibody in development for the treatment of relapsed/refractory (R/R) high-risk myelodysplastic syndromes (HR-MDS). It is the most advanced therapeutic candidate targeting galectin-9, which is an important oncogenic driver and potent immunosuppressor that plays a central role in some of the most difficult-to-treat cancers. With its mutation-agnostic, dual mechanism of action, LYT-200 is designed to address both the malignant cells and the immunosuppressive environment that sustain disease. LYT-200 has been granted Fast Track designation from the U.S. Food and Drug Administration (FDA) for the treatment of R/R HR-MDS in combination with a hypomethylating agent. LYT-200 has also been granted Fast Track designation from the U.S. FDA for the treatment of acute myeloid leukemia (AML). Gallop Oncology is a clinical-stage biotechnology company dedicated to transforming the treatment paradigm for hematological malignancies. Its lead candidate, LYT-200, is a first-in-class, mutation-agnostic antibody in development for the treatment of relapsed/refractory (R/R) high-risk myelodysplastic syndromes (HR-MDS). Gallop Oncology was founded by and is currently wholly owned by PureTech Health plc (LSE: PRTC). PureTech Health is a hub-and-spoke biotherapeutics company dedicated to giving life to science and transforming innovation into value. We do this through a proven, capital-efficient R&D model focused on opportunities with validated pharmacology and untapped potential to address significant patient needs. This strategy has produced dozens of therapeutic candidates, including three that have received U.S. FDA approval. By identifying, shaping, and de-risking these high-conviction assets, and scaling them through dedicated structures backed by external capital, we accelerate their path to patients while creating sustainable value for shareholders. Amer Zeidan, MBBS, MHS, has received honoraria from PureTech in his role as a clinical advisor. The views and opinions expressed are his own and do not necessarily reflect those of his employer. The content above comes from the network. if any infringement, please contact us to modify.

急性髓系白血病耐药难控？临床试验新药提供破局新方向 📖 阅读提示：要是你或者家人不幸确诊急性髓系白血病，却因为年纪大、基础病多耐受不了强化疗，或是好不容易缓解了又耐药复发，手里连可选的方案都没有，是不是觉得天都快塌了？这几年针对不同分型的急性髓系白血病创新药临床试验相继落地，给很多走投无路的人带来了更低毒、更有效的治疗新选择。今天咱们就从耐药的核心原因说起，把近期的研究进展和能摸到的临床试验项目说透，帮你理清接下来的治疗思路。 一、急性髓系白血病的发病现状与生存困境 📌 我国急性髓系白血病年发病率约2.3/10万，60岁以上老年患者占比超60%，3年总生存率不足20% 这个病之所以这么难缠，本质上是癌细胞里的两个“坏分子”在作祟：一个是FLT3突变，相当于给癌细胞开了“无限增殖外挂”，让它没日没夜地分裂扩散；另一个是BCL-2通路异常，等于给癌细胞穿了“免死金牌”，躲着免疫系统的追杀，这俩也是绝大多数人耐药复发的核心元凶。 咱们国家每年每10万人里就有2.3个人确诊，其中60%以上都是60岁以上的老年人，整体3年总生存率还不到20%。差不多4成刚确诊的人，因为年纪大、有高血压糖尿病这些基础病，连强化疗的门槛都碰不到；还有超过5成的人，好不容易第一次治疗缓解了，转头就复发耐药，手上根本没药用。要是你刚好携带明确的驱动突变，复发风险比没突变的人高2-3倍，很多人刚拿到确诊报告，先听到的就是一句“没有太合适的方案”，那种走投无路的滋味，想想都难熬。 二、传统治疗的局限与患者痛点 客观来看：强化化疗方案初治缓解率可达60%，但老年/不耐受患者3级以上不良反应发生率超80%，治疗相关生命终点率达15%-20% 咱们先说说大家最熟悉的化疗：刚确诊的人用强化疗，第一次缓解率能到60%，但放在老年、耐受不了的人群里，3级以上的严重不良反应发生率超过80%，每100个人里就有15到20个，最后还有一点不是因为病走的，是扛不住治疗相关的并发症。 化疗的逻辑是“好坏细胞一起杀”，带来的严重骨髓抑制、上吐下泻的副作用，本来就有基础病的老年人根本扛不住，不少人怕拖累家人，硬生生放弃了治疗。之前的老靶向药也不给力，能覆盖的突变亚型少，还容易“打偏”，也就是医生说的脱靶效应，一旦耐药了连标准的二线方案都找不到，复发的人中位生存期还不到6个月，不少家庭夹在“治不好、治不起”的两难里，走一步算一步。 三、不同治疗阶段的耐药应对方案怎么选 这几年大家也能感觉到，急性髓系白血病的治疗早就不是“化疗全覆盖”的老路子了，现在都是盯着你的分型和突变精准用药，针对BCL-2、FLT3这些靶点的新药，已经被CSCO指南列在优先推荐的位置。 这些药不是瞎杀细胞，专门盯着癌细胞的“命门”打，不仅耐药概率低、缓解的程度更深，副作用还比化疗小太多，你不用天天躺床上扛着吐，吃不下饭，生活质量能提一大截。但问题也摆在这：刚上市的创新药价格都不低，绝大多数还没纳入医保，普通家庭要长期用真的扛不住，哪怕砸锅卖铁也撑不了几个月。 要是你符合适应症，其实可以考虑走临床试验的通道，不仅能提前用到还没上市的前沿新药，有专门的研究团队定期跟进你的情况，药费和相关的检查费都不用你出，能省一大笔开销。现在这个病的治疗难点，主要就是两个：一个是老年人耐受不了强化疗，另一个是有突变的患者容易复发耐药，现有的标准方案连一半人的需求都覆盖不到。好在这两年国内血液肿瘤的新药研发跑得很快，针对不同分型、不同治疗阶段的临床试验都在落地，从刚确诊的到复发难治的全周期都能覆盖，下面给大家把目前在开的5个项目说透。 五项临床试验新药深度解读与机会 📋维奈克拉联合阿扎胞苷治疗初治不适合强化化疗的急性髓系白血病III期临床研究 项目简介 试验登记号：CTR20200493 药物类别：Bcl-2抑制剂联合去甲基化药物 试验分期：III期 申办方：艾伯维医药贸易（上海）有限公司 招募人群：初治不适合强化化疗的急性髓系白血病患者 试验药物介绍 维奈克拉是专门盯着BCL-2这个“免死金牌”打的抑制剂，相当于直接把癌细胞的“保命通道”给焊死，让它没法逃避免疫系统的清除；阿扎胞苷是去甲基化药物，相当于把癌细胞脸上涂的“伪装涂料”给刮掉，让免疫细胞一眼就能认出这个坏东西，两个药搭着用，从根上就能降低耐药突变的概率。 目前的数据显示，这个联合方案的完全缓解率能到37%，比单用阿扎胞苷翻了一倍，中位总生存期能到14.7个月，比单药拉长了快一倍，更关键的是，3级以上不良反应的发生率和单用阿扎胞苷没差别，疗效和安全都顾到了，特别适合基础病多、耐受不了化疗的老年人。 设计方案 多中心、随机、双盲、平行对照，按1:1随机分为试验组（维奈克拉+阿扎胞苷）和对照组（安慰剂+阿扎胞苷），28天为1周期，给药直至疾病进展或不可耐受毒性。 筛选入排要求与患者权益 上述项目内容展现有限，详细的筛选要求和入排标准以及你能享有的权益请点击链接详细咨询了解。 📋阿扎胞苷治疗老年/不耐受强化化疗的初治急性髓系白血病III期注册临床研究 项目简介 试验登记号：CTR20171498 药物类别：去甲基化药物 试验分期：III期 申办方：正大天晴药业集团股份有限公司 招募人群：老年/不耐受强化化疗的初治急性髓系白血病患者 试验药物介绍 阿扎胞苷作为去甲基化药物，不仅能刮掉癌细胞的伪装，让免疫系统精准击杀，还能直接掐断癌细胞的增殖信号，不让它再分裂长新的，耐药的概率也更低。 目前的数据显示，这个方案的完全缓解率有23.4%，比传统的姑息治疗翻了3倍，中位生存期能到10.2个月，比姑息治疗多活了6个月，副作用大多是轻度的恶心拉肚子，重度不良反应比强化疗少了70%，安全性高、耐受度好，身体弱、基础病多的老人也能扛得住。 设计方案 多中心、开放、阳性药对照，按1:1随机分为试验组（阿扎胞苷单药）和对照组（传统姑息化疗/支持治疗），28天为1周期，给药至多6个周期，后续可维持治疗。 筛选入排要求与患者权益 上述项目内容展现有限，详细的筛选要求和入排标准以及你能享有的权益请点击链接详细咨询了解。 📋Quizartinib（奎扎替尼）单药治疗FLT3-ITD突变复发/难治急性髓系白血病II期临床研究 项目简介 试验登记号：CTR20240999 药物类别：高选择性FLT3抑制剂 试验分期：II期（招募中） 申办方：第一三共（中国）投资有限公司 招募人群：FLT3-ITD突变的复发/难治性急性髓系白血病患者 试验药物介绍 奎扎替尼是高选择性的FLT3抑制剂，专门抓FLT3-ITD突变的蛋白，就像带了精准定位的导弹，只打突变的坏蛋白，不碰正常细胞，相当于直接把癌细胞的“增殖开关”给掰断，诱导癌细胞自己凋亡，脱靶的副作用和耐药风险都低很多。 目前的数据显示，单药的完全缓解率能到47%，比传统的二线化疗翻了3倍，中位无进展生存期有8.3个月，比化疗多了5个月，3级以上不良反应发生率比化疗降低60%。而且是口服药，不用天天住院扎针，后线耐药、身体状态差的人也能用，不用来回跑医院折腾。 设计方案 多中心、单臂、开放标签，所有入组患者均接受奎扎替尼单药治疗，28天为1周期，给药直至疾病进展或不可耐受毒性。 筛选入排要求与患者权益 上述项目内容展现有限，详细的筛选要求和入排标准以及你能享有的权益请点击链接详细咨询了解。 📋富马酸吉瑞替尼对比挽救化疗治疗FLT3突变复发/难治急性髓系白血病III期注册临床研究 项目简介 试验登记号：CTR20200247 药物类别：FLT3抑制剂 试验分期：III期 申办方：安斯泰来制药（中国）有限公司 招募人群：FLT3突变的复发/难治性急性髓系白血病患者 试验药物介绍 吉瑞替尼是个“双杀”的FLT3抑制剂，不管是FLT3-ITD还是FLT3-TKD这两种最常见的突变，它都能盯上，精准把带突变的癌细胞清干净，几乎碰不到正常细胞，耐药的概率更低。 目前的数据显示，用这个药的患者中位总生存期能到9.3个月，比挽救化疗多了近4个月，完全缓解率有34%，比化疗翻了一倍，3级以上不良反应主要为可控的血液学毒性，发生率比化疗降低30%，覆盖的突变亚型广，不管你是哪种FLT3突变的复发难治患者，都能考虑。 设计方案 多中心、随机、开放、平行对照，按1:1随机分为试验组（吉瑞替尼单药）和对照组（标准挽救化疗），28天为1周期，给药直至疾病进展或不可耐受毒性。 筛选入排要求与患者权益 上述项目内容展现有限，详细的筛选要求和入排标准以及你能享有的权益请点击链接详细咨询了解。 📋索拉非尼联合化疗治疗伴FLT3突变初治急性髓系白血病II期临床研究 项目简介 试验登记号：CTR20211214 药物类别：多靶点酪氨酸激酶抑制剂联合化疗 试验分期：II期（招募完成） 申办方：国内血液肿瘤领域创新药企 招募人群：伴FLT3突变的初治急性髓系白血病患者 试验药物介绍 索拉非尼是多靶点的酪氨酸激酶抑制剂，不仅能掐断FLT3突变的增殖信号，还能抑制肿瘤周围的新生血管生长，相当于把癌细胞的“粮道”给断了，和化疗搭着用，还能把藏得很深的肿瘤干细胞一起清掉，降低复发的概率，缓解的程度比单纯化疗深太多。 目前的数据显示，这个联合方案的完全缓解率能到62%，比单纯化疗翻了快一倍，2年无病生存率有41%，比单纯化疗高了25个百分点，不良反应整体都可控，特别适合身体状态还可以、有移植计划的初治突变患者，能帮你在移植前达到更深的缓解，降低移植后复发的风险。 设计方案 多中心、单臂、开放标签，所有入组患者均接受索拉非尼联合标准化疗方案治疗，28天为1个诱导治疗周期，后续巩固治疗按研究方案执行。 筛选入排要求与患者权益 上述项目内容展现有限，详细的筛选要求和入排标准以及你能享有的权益请点击链接详细咨询了解。 想了解更多治疗、临床研究相关内容，可以点击以下链接阅读往期文章： 血液系统肿瘤诊疗科普 | 【白血病/淋巴瘤/骨髓瘤/MDS选择】药物临床试验合规知识全解 血液系统性肿瘤-药物临床试验受试者信息 |【白血病/淋巴瘤/多发性骨髓瘤/骨髓增生异常综合征】| 全国多中心已备案项目 血液系统性肿瘤-药物临床试验受试者信息 |【白血病/淋巴瘤/多发性骨髓瘤/骨髓增生异常综合征】| 全国多中心已备案项目 【白血病】你值得被认真对待、被全力救治！白血病难治 / 复发患者，不用怕，别放弃，26年第三批6款临床试验新药，让每一份坚持都有回应 【白血病】造血干细胞移植是唯一的根治方法吗，什么情况下需要做移植？2026年第二批白血病临床试验新药；破局全新治疗方法，重获希望 2026年最新【白血病】6款临床试验新药，白血病患者的福音、攻克指日可待、现招募白血病患者参加新药临床实验治疗，提前享受医学成果 康心医疗｜【白血病】12月临床试验新药治疗汇总：攻克白血病困境！5项创新临床研究，为生命重燃希望最后还有一点想和大家说几句掏心窝子的 急性髓系白血病的治疗早就不是只有化疗一条死路了：刚确诊耐受不了化疗的老人，有FLT3突变复发难治的人，都有对应的精准方案可以选。我知道很多人一听到临床试验就犯怵，觉得是去当“小白鼠”，其实真不是，所有临床试验都要过严格的伦理审查，只有前期在实验室和小范围人群里验证过安全有效的药，才能进入到临床研究阶段，对你要是已经没有更好的治疗方案了，真的是非常值得考虑的新出路。 目前该领域有多项临床试验正在全国多中心开展，如果大家想咨询报名或不确定自己是否符合上述临床试验的入组条件，再或者想要了解更多该疾病的临床试验项目，可以私信联系我们或者点击下面图片小程序咨询了解详情，我们将会免费为您提供一对一的病情评估和入组指导等服务。一起少走抗癌弯路。 本文围绕急性髓系白血病的发病现状、传统治疗局限、耐药应对策略展开，深度解读了5项针对不同分型、不同治疗阶段的前沿临床试验新药，覆盖初治不耐受化疗、FLT3突变复发难治等多类人群，为大家提供更低毒、更有效的治疗新选择参考。 你或身边的亲友在急性髓系白血病治疗过程中遇到过哪些难点？2. 你对临床试验还有哪些疑问？欢迎在评论区留言交流。 #急性髓系白血病 #血液肿瘤 #临床试验 #靶向药 #耐药应对 ⚠️免责声明：本文仅为医学科普，不属于医疗广告。临床试验为医学科学研究，不保证受试者获得临床获益，存在未知风险。能否参加研究，必须由研究中心结合病历综合评估，提交信息不等于可以入组。文中提及补贴均为受试者交通、采血营养补偿。