This phase I trial studies the safety, side effects, and best dose of ADG126, in combination with ivonescimab alone, in combination with ivonescimab, leucovorin, and fluorouracil, or in combination with ivonescimab and leucovorin, fluorouracil, and irinotecan (FOLFIRI regimen) in treating patients with microsatellite stable (MSS) colorectal cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as ivonescimab and ADG126, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ivonescimab may also stop or slow the cancer by blocking the growth of new blood vessels necessary for tumor growth. Leucovorin calcium is a type of drug called a folic acid analog, which means it is similar to the vitamin folic acid. It is used in combination with certain chemotherapy drugs to enhance their ability to kill tumor cells or to lessen their harmful side effects. Fluorouracil is a type of chemotherapy called an antimetabolite, which is a drug that mimics a natural chemical and prevents its use in cells. It interferes with the production of a key component of deoxyribonucleic acid (DNA), which prevents the DNA from copying itself. This causes tumor cells and other rapidly dividing cells to die. Fluorouracil also gets incorporated into ribonucleic acid (RNA) and DNA, disrupting critical cell functions. Irinotecan is in a class of antineoplastic medications called topoisomerase I inhibitors. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Giving ADG126 with ivonescimab, with or without leucovorin and fluorouracil or FOLFIRI regimen, may be safe in treating patients with MSS advanced/metastatic colorectal cancer.

开始日期2026-07-21

申办/合作机构

City of Hope National Medical Center

[+1]

NCT07437287

/ Not yet recruiting临床2/3期IIT

Countering Immunotherapy Resistance With Novel Combinations in Advanced Biliary Tract Cancers

The goal of this clinical trial is to etablish whether adding Mitazalimab to standard chemotherapy is more effective than standard chemotherapy alone in people with advanced bile duct cancer. It will also learn about the safety of Mitazalimab.
The main questions it aims to answer are:
* Does the addition of Mitazalimab enhance efficacy?
* What medical problems do participants have when taking Mitazalimab + mFOLFOX?
Participants will:
* Take drug mFOLFOX every two weeks until disease progression or mFOLFOX every two weeks plus mitazalimab in addition to mFOLFOX, with a first injection 7 days before the first mFOLFOX chemotherapy and then 3 days after the start of each mFOLFOX cycle.
* Visit the clinic once every 2 weeks for checkups and tests
* Have a radiological assessment every 8 weeks during treatment. After stopping treatment, participants will be monitored at the hospital every 8 weeks if no progression is observed, or every 12 weeks after disease progression.

开始日期2026-07-01

申办/合作机构

UNICANCER

[+1]

NCT07271355

/ Not yet recruiting临床3期IIT

Investigation of Mitomycin C PIPAC - FOLFIRI Combination for Unresectable Appendiceal or Colorectal Peritoneal Metastases Treatment (IMPACT): A Multicenter, Randomized, Open-Label, Phase 3 Trial

This phase III trial studies how well pressurized intraperitoneal aerosolized chemotherapy (PIPAC) with mitomycin works versus (vs) standard chemotherapy (leucovorin calcium, fluorouracil, and irinotecan hydrochloride [FOLFIRI regimen] plus bevacizumab) in treating patients with appendix or colorectal cancer that cannot be removed by surgery (unresectable) and has spread from where it first started (primary site) to the abdominal cavity (peritoneal metastases). PIPAC is a new therapeutic approach that is minimally invasive, does not require surgery (laparotomy), and can be frequently repeated. Chemotherapy is delivered as a pressurized mist directly inside the abdominal cavity (peritoneum) during a minimally invasive surgery called a laparoscopy. The pressure helps the chemotherapy absorb into the cancer tissue and spread more evenly. Mitomycin is an antibiotic used as a chemotherapy drug. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their deoxyribonucleic acid (DNA). Standard chemotherapy drugs, such as those in the FOLFIRI regimen, are given via infusion into a vein (intravenously), and work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Another standard intravenous drug, bevacizumab, is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Giving mitomycin via PIPAC in combination with the standard FOLFIRI regimen, with or without bevacizumab, may work better than standard FOLFIRI plus bevacizumab alone in treating patients with unresectable appendix or colorectal cancer with peritoneal metastases.

开始日期2026-07-01

申办/合作机构

City of Hope National Medical Center

[+1]

100 项与亚叶酸钙相关的临床结果

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100 项与亚叶酸钙相关的转化医学

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100 项与亚叶酸钙相关的专利（医药）

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10,324

项与亚叶酸钙相关的文献（医药）

2026-04-01·EJSO

Targeting the liver: Insights from a tertiary center on post-operative hepatic arterial oxaliplatin for metastatic colorectal cancer

Article

作者: Pudlarz, Thomas ; Sarti, Kevin ; Denèche, Imène ; Ducreux, Michel ; Gelli, Maximiliano ; Malka, David ; Bonnet, Baptiste ; Hollebecque, Antoine ; El-Rawadi, Elsa ; Boilève, Alice ; Valéry, Marine ; Smolenschi, Cristina ; Tselikas, Lambros ; Camilleri, Géraldine M ; Fuerea, Alina ; Tarabay, Anthony ; Fernandez De Sevilla, Elena ; Boige, Valérie ; Beunon, Paul

BACKGROUND:

As the liver is the most common site of metastasis in colorectal cancer (CRC), and metastatic recurrence frequently occurs after resection of colorectal liver metastases (CRLM), hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising treatment approach. This study investigates the feasibility, safety, and efficacy of postoperative HAIC with oxaliplatin following curative-intent resection of CRLM.

METHODS:

A retrospective analysis was conducted on all patients with resected CRLM who received postoperative HAIC with oxaliplatin between 2008 and 2022 at a tertiary cancer center. The primary study endpoint were disease-free-survival (DFS) and overall survival (OS).

RESULTS:

Overall, 119 patients (median age, 56 years; synchronous metastatic disease, 82%) received postoperative HAIC with oxaliplatin after complete resection of their CRLM (median number of metastases resected, 7). They received a median number of 6 HAIC cycles (range, 1-12), mostly combined with intravenous chemotherapy with 5-fluorouracil/leucovorin (n = 118, 99%) and irinotecan (n = 41, 34%). The median DFS was 10.2 months (95% CI 9-12.4) and the median intrahepatic DFS was 18.4 months (95% CI 12.4-29.7,12 months DFS rate, 60%). The median OS reached 55.5 months (95% CI, 50.0-86.6; 5-year OS rate, 46%). Grade 3-4 toxicities occurred in 45% of patients (neutropenia, 38%; peripheral neuropathy, 9%); 54% of patients experienced pain (mostly mild to moderate) during oxaliplatin infusion. HAI catheter-related complications included extrahepatic perfusion (30%) and catheter occlusion (11%).

CONCLUSIONS:

HAIC with oxaliplatin is an effective, safe and feasible treatment option after resection/ablation of CRLM. These findings support the therapeutic relevance of postoperative HAIC in liver-limited metastatic CRC.

2026-04-01·CURRENT OPINION IN PEDIATRICS

Clinical concerns and considerations for leucovorin use in autism spectrum disorder

Review

作者: Ravikoff, Lillian Maidman ; Mekhail, Joseph ; Howard, Caroline ; Milanaik, Ruth

Purpose of review:

To provide pediatric clinicians with an overview of current research on leucovorin use in children with autism spectrum disorder (ASD) and a guide to patient evaluation and treatment.

Recent findings:

An association between cerebral folate deficiency (CFD) and ASD has been suggested in some studies. Autoantibodies that block folate entry into the brain are a cause of CFD and have been detected in 71% of patients with ASD. Leucovorin is a synthetic drug that increases folate concentrations in the brain despite the presence of autoantibodies. Certain studies have indicated reductions in communication deficits in nonverbal children with ASD, particularly those with these autoantibodies, following consistent leucovorin use. However, other studies have found no change in symptoms despite leucovorin intake. The American Academy of Pediatrics (AAP) currently does not recommend use of leucovorin in children with ASD.

Summary:

Due to recent popularity among policymakers and on social media, many pediatricians have reported increased requests by families for leucovorin prescriptions to treat ASD in pediatric patients. This review provides clinicians with an overview of the biological rationale, clinical evidence, and potential benefits and limitations of leucovorin use in children with ASD.

2026-03-10·JOURNAL OF CLINICAL ONCOLOGY

Thromboembolic Events During Perioperative Therapy for Resectable and Borderline Resectable Pancreatic Cancer in the PREOPANC-2 Trial

Article

作者: ten Cate, Hugo ; Wit, Fennie ; Patijn, Gijsbert A. ; van Eijck, Casper H.J. ; Janssen, Quisette P. ; Cirkel, Geert A. ; Veenstra, Maaike K. ; Nieuwenhuijs, Vincent B. ; Coene, Peter-Paul L.O. ; van Dam, Jacob L. ; Rompen, Ingmar F. ; Wilmink, Johanna W. ; Valkenburg-van Iersel, Liselot ; Nuyttens, Joost J.M.E. ; de Groot, Jan Willem B. ; Homs, Marjolein Y.V. ; Brouwer-Hol, Lieke ; Streppel, Mirte M. ; Loosveld, Olaf J.L. ; Kazemier, Geert ; Bruynzeel, Anna M.E. ; Mekenkamp, Leonie J.M. ; Bonsing, Bert A. ; Groot Koerkamp, Bas ; Luelmo, Saskia A.C. ; Liem, Mike S.L. ; Bosscha, Koop P. ; Haberkorn, Brigitte C.M. ; van der Harst, Erwin ; Busch, Olivier R. ; van Es, Nick ; Willems, Ruth A.L. ; Stommel, Martijn W.J. ; de Laat, Bas ; van Diepen, Aniek E. ; de Wilde, Roeland F. ; Michiels, Nynke ; Bouwense, Stefan A.W. ; Droogh, Daphne H.M. ; Verkolf, Eva M.M. ; Dekker, Esther N. ; ten Tije, Albert J. ; Besselink, Marc G. ; van Eijck, Casper W.F. ; van Tienhoven, Geertjan ; Theijse, R.T. ; Zonderhuis, Barbara M. ; Roest, Mark ; de Vos-Geelen, Judith ; van Santvoort, Hjalmar C. ; de Wilde, Anouk J. ; Strijbos, Bo T.M. ; Bos, Hendrik ; de Hingh, Ignace H.J.T. ; Versteijne, Eva ; van der Kolk, Marion B. ; Stoop, T.F. ; Luyer, Misha D.P. ; Vrijaldenhoven, Suzan ; Hermans, Karlijn E.P.E. ; Karsten, Tom M. ; van Bekkum, Marlies L. ; Beerepoot, Laurens V. ; Mieog, J. Sven D. ; ten Oever, D.

PURPOSE:

Pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of venous thromboembolism (VTE), which is burdensome and associated with decreased survival. Although neoadjuvant treatment is increasingly used in patients with PDAC, data on VTE in this setting remain scarce. This study evaluated VTE incidence during (neo)adjuvant therapy for resectable and borderline resectable PDAC and its relation to survival.

METHODS:

This study included patients from the investigator-initiated, multicenter, randomized controlled phase III PREOPANC-2 trial. Patients were randomly assigned to neoadjuvant 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin followed by surgery (FFX arm) or neoadjuvant gemcitabine-based chemoradiotherapy (CRT), followed by surgery and adjuvant gemcitabine (CRT arm). VTE was defined as both incidental and symptomatic lower- or upper-extremity deep vein thrombosis, pulmonary embolism (PE), splanchnic vein thrombosis, and catheter-related thrombosis. VTE occurrence was retrospectively evaluated from random assignment to 12 months after random assignment. The association with overall survival (OS) was analyzed using Cox regression analysis.

RESULTS:

VTE was diagnosed in 28 of 325 patients (9%): nine (3%) preoperatively and 19 (8%) postoperatively. Most VTEs were symptomatic (54%). Although a higher proportion of patients developed postoperative VTE in the CRT arm (FFX 3% v CRT 12%, P = .02), the 12-month cumulative incidence did not differ between arms (6% v 11%, P = .06). Two patients died from PE-related causes in the CRT arm. VTE was independently associated with reduced OS (adjusted time-varying hazard ratio, 2.13, P = .002).

CONCLUSION:

VTE occurred in 9% of patients with (borderline) resectable PDAC undergoing (neo)adjuvant treatment in the year after random assignment and was associated with decreased OS. These results underscore the need for standardized reporting of thromboembolic events in clinical trials and future studies assessing the potential benefits of thromboprophylaxis during neoadjuvant therapy.

667

项与亚叶酸钙相关的新闻（医药）

2026-04-01

·赞Med

点击上方“蓝字”关注我们吧！引言慢性气道疾病（哮喘、慢性阻塞性肺疾病、支气管扩张症和囊性纤维化等）的病理生理机制存在重叠，其中黏液生成、组成和清除的异常是导致症状、气流受限、急性加重和疾病进展的关键临床因素。本期基于2026年1月发表于《Drugs》的一篇综述[1]，探讨黏液作为贯穿多种慢性气道疾病的“可治疗特质”，在疾病表型分析、疾病负担评估及靶向干预改善预后中的核心作用。 1 黏液作为可治疗特质的临床价值 “可治疗特质”是基于精准医学理念的个体化治疗策略，旨在识别出不同疾病中可测量且具有临床意义的特征并予以靶向干预。黏液作为上述可治疗特质，其过量产生与清除障碍已成为多种慢性气道疾病进展的核心驱动因素。黏液高分泌、流变学特性改变和黏液纤毛清除（MCC）功能受损，可导致气道阻塞、黏液栓形成、反复感染、炎症加剧和临床结局恶化。黏液栓是增厚黏液的密集聚积物，可阻塞气道，是具有临床意义但常被低估的病理表现——即黏液动力学受损的后果之一（图1）。最新影像学研究表明，黏液栓见于25%-67%的慢性阻塞性肺疾病（COPD）患者和58%的哮喘患者，且常持续存在，可在同一支气管肺段滞留数年，成为预测疾病进展、急性加重和死亡率的独立因素。图1 慢性气道疾病中的黏液病理学与栓塞形成 2 不同疾病中黏液异常的病理特征黏液异常在不同慢性气道疾病中呈现独特的分子和生物物理特征（图2）。哮喘中，白细胞介素-4（IL-4）、IL-5和IL-13驱动的2型（T2）炎症诱导杯状细胞增生和MUC5AC过量产生。活化的嗜酸性粒细胞释放的过氧化物酶催化氧化剂形成，交联黏蛋白巯基使黏液凝胶变硬，Charcot-Leyden晶体和细胞外DNA进一步增加黏度，共同促进黏液栓形成。黏液栓常见于重症哮喘，与FEV₁降低和急性加重风险增加相关，且常伴随痰嗜酸性粒细胞增多和FeNO升高。 COPD（尤其慢性支气管炎表型）中，杯状细胞增生和黏膜下腺肥大导致浓缩的黏液富集MUC5AC和MUC5B，损害MCC功能。中性粒细胞炎症通过释放细胞外DNA和蛋白酶进一步增加黏液黏度，加重清除缺陷。慢性黏液高分泌与急性加重频率增加、肺功能加速下降和更高死亡率相关。支气管扩张症的特征是MCC受损和脓性、富含中性粒细胞的分泌物。中性粒细胞弹性蛋白酶等蛋白酶驱动组织损伤，浓缩黏液富集MUC5B、MUC5AC和促炎介质（如IL-1β），损害MCC功能并促进黏液栓塞，形成感染-炎症-黏液滞留的恶性循环，驱动渐进性气道损伤和重塑。 CF中，CFTR介导的离子转运缺陷导致气道表面液体耗竭，产生黏弹性和内聚力增加的高度浓缩黏液（固体含量约10%），损害MCC功能。慢性中性粒细胞炎症产生的氧化剂增加MUC5B和MUC5AC的二硫键交联，进一步硬化黏液。分泌前即存在的黏蛋白内在缺陷与分泌后变化共同作用，即使在患者无感染时，滞留的黏液也会引发炎症，形成维持细菌定植、放大黏液产生并驱动进行性结构性肺损伤的微环境。图2 哮喘、COPD、支气管扩张症和CF病理生理学中的核心——黏液异常 3 靶向黏液的干预治疗——黏液溶解剂慢性气道疾病中黏液治疗的主要目标是降低黏液黏度、改善气道水合作用及改善MCC。黏液的有效管理需采用多模式策略，包括药物治疗、非药物干预和生活方式调整。支气管扩张剂和抗炎药通过干扰其他生理机制间接影响黏液，而黏液溶解剂（如NAC）则直接针对黏液进行治疗干预，其通过断裂黏蛋白中的二硫键来降低黏液黏度，促进痰液排出。在COPD中，NAC可适度降低急性加重率和住院率，尤其在频繁急性加重和慢性支气管炎表型患者中获益最大。美国胸科学会和欧洲呼吸学会（ERS）建议将黏液溶解剂作为COPD的附加疗法，尤其适用于上述获益人群，高剂量治疗（如NAC 600mg 2次/日）效果优于低剂量。GOLD指南也支持将其用于特定COPD患者，特别是未接受吸入性糖皮质激素（ICS）治疗的患者。在支气管扩张症中，NAC及其他黏液溶解剂的证据尚不一致。近期一项注册分析提示高剂量NAC（1200 mg/日）可能优于低剂量，但目前高质量证据尚不支持将其作为常规单药治疗。2025年ERS指南强调，黏液活性治疗宜作为全面气道廓清方案和规律体育锻炼的组成部分。通过黏液活性药物促进痰液移动，与机械性气道廓清技术协同以实现临床获益。哮喘方面，临床前和转化研究显示破坏黏蛋白二硫键可缓解黏液栓塞和气道高反应性，但尚无随机对照试验证明黏液溶解剂在哮喘患者中的临床疗效，目前不推荐用于常规治疗。 CF中，临床试验和系统评价显示，口服或雾化硫醇衍生物（包括NAC）与安慰剂相比未显著改善肺功能、急性加重率或生活质量。虽然高剂量口服NAC可能调节炎症并改善谷胱甘肽水平，但并未在相关研究中观察到这些效应转化为肺功能或急性加重的临床获益。 4 最新研究进展与未来方向近年来，黏液靶向治疗的研究取得了多项新进展。多种新型黏液溶解剂如Fexlamose（硫醇-糖化合物，可破坏黏蛋白二硫键以降低痰液弹性）、P3001（小分子黏蛋白减少剂）、dPGS-SH（兼具减少黏蛋白多聚化与抗炎特性）、Icenticaftor（CFTR增效剂）及OligoG CF-5/20（通过钙离子螯合调节黏液结构）等正处于研发或临床试验阶段。介入技术层面，液氮冷冻喷雾、支气管成形术、靶向肺去神经术等减少杯状细胞增生的支气管镜干预措施正在评估中。影像学领域值得关注的进展是AI自动量化技术的应用，可实现快速、可重复的全肺黏液栓量化，并在近万名吸烟者中验证了其与死亡率的关联。GOLD 2026报告指出AI辅助方法是前景广阔的工具，但需进一步验证和标准化。 5 精准医疗框架下的黏液靶向策略上述研究进展为黏液作为可治疗特质的临床应用奠定了坚实基础。如图3所示，黏液高分泌符合可治疗特质的既定标准：可通过临床表型分析和影像学识别，可使用经验证工具测量，具有临床相关性（预测急性加重、肺功能下降和死亡率），且可靶向调节。图3 概念框架：黏液高分泌作为贯穿多种气道疾病的“可治疗特质” 在此框架下，精准医疗的核心在于将治疗机制与疾病病理生理相匹配，针对不同内分型患者，需采用差异化的干预策略：如基于黏液特性的NAC等黏液溶解剂选择、CF中的CFTR调节剂治疗及T2-高表达哮喘中的抗IL-13生物制剂。【总结】黏液高分泌作为多种慢性气道疾病的核心病理环节，具备可识别、可测量、与预后相关且可靶向干预的临床价值。NAC作为直接作用于黏液性状的干预药物，在COPD频繁急性加重及慢性支气管炎表型患者以及支扩患者中的获益已获指南认可，高剂量方案值得临床关注。未来，将黏液表型分析整合至临床实践，依据炎症和黏液纤毛内分型进行患者分层，有望推动以可治疗特质为导向的慢性气道疾病精准管理，实现真正个体化治疗。随着新型黏液溶解剂的研发、AI影像技术成熟及多组学分析的深入，黏液作为可治疗特质的临床价值将进一步释放，为广大患者带来更多临床获益。参考文献： [1] Cazzola, M., Rogliani, P., Ora, J. et al. Mucus as a Treatable Trait in Chronic Airway Diseases. Drugs. 2026 Apr;86(4):443-463.

2026-03-31

·深圳大百汇生命健康产业园

“汇”报 | 生命与健康产业研究月报（3月）

融投与合作空山慈科技完成Pre-A轮融资，加速脑机交互神经调控平台临床转化近日，专注无创脑机接口与神经调控的上海空山慈科技有限公司（以下简称“空山慈科技”）宣布完成Pre-A轮融资。本轮由云启资本独家领投，所募资金将主要用于核心技术研发、临床转化及全球化拓展。程天科技再获亿元级B+轮融资，加速外骨骼“人机融合”新消费时代杭州程天科技发展有限公司（以下简称“程天科技”）完成了亿元级B+轮融资，此为公司在一年内连续完成的第二轮融资。本轮由农银资本领投，汇川产投、杭州资本跟投。易慕峰完成近2亿元Pre-IPO轮融资，聚焦实体瘤治疗领域全球创新型细胞治疗公司易慕峰生物完成近2亿元人民币Pre-IPO轮融资。本轮融资由高榕创投、济峰资本领投，深天使、明道投资共同参与，老股东约印医疗基金持续加注。亦立医药完成新一轮近亿元人民币融资，加速推进新靶点项目研发与临床转化 3月12日，杭州亦立医药有限公司（以下简称“亦立医药”）宣布完成新一轮近亿元人民币融资，本轮融资由隆峰创投、亦成投资、弘盛资本、贝壳基金共同投资。所募资金将主要用于支持公司新靶点项目的分子发现、技术平台建设与临床转化，助力创新管线向临床阶段稳步迈进。炫景生物完成超2亿元Pre-A轮融资 2026年3月20日，临床阶段的小核酸药物公司炫景生物宣布，完成由康君资本领投的超2亿元Pre-A轮融资，德联资本、华泰金斯瑞基金、金易赋新、国海创新资本、联想创投和现有股东元希海河共同参与本轮投资。博思得完成超亿元C轮融资，领跑国产医疗核心部件赛道苏州博思得电气有限公司（以下简称“博思得”）作为国内X光影像核心部件领军企业，宣布完成超亿元C轮融资，由上海瑞力领投，交银资本、元璟资本等跟投。政策法规 2026年政府工作报告释放三大医疗政策信号首先，优化医疗机构功能定位和布局。近年来，卫健系统持续推进医疗资源优化布局。2026年全国卫生健康工作会议进一步明确“强基、稳二、控三”的原则，系统概括了当前的工作方向。通过严格控制三级医院的院区数量、床位规模等，抑制其无序扩张，有助于缓解大医院对人才和患者的“虹吸效应”。同时，需要持续提升基层诊疗能力，使常见病、多发病在基层能够得到有效诊治。其次，打造生物医药新兴支柱产业。当前，生物医药产业界一方面持续加大科技创新力度，针对新靶点、新化合物、新机制开展科技攻关，在继续发挥快速跟随优势的同时，做更多原始创新方向的突破；另一方面正加速推进国际化，通过多种方式开拓海外市场，中国的生物医药产业正站在全球化的起点，未来中国生物医药产业在全球的市场份额有望大幅提升。最后，优化医药集中采购。医药集采旨在通过压缩药品流通环节成本，直接降低群众用药负担，提升医保基金使用效率，引导医保为药品的临床价值付费。同时，该政策也致力于形成市场倒逼机制，推动医药企业转向创新驱动发展。2025年以来，国家医保局在持续优化集采规则，在2025年10月开展的第十一批集采中，国家设置了“锚点价”避免极端低价。目前，医药集中采购已进入优化新阶段，政策导向从灵魂砍价转向稳临床、保质量、防围标、反内卷的系统重构。创新与研发罗氏单抗疗法达肾病3期试验主要终点罗氏（Roche）近日宣布，其在成人原发性膜性肾病患者中开展的3期MAJESTY研究已达到主要终点。研究结果显示，与活性对照相比，接受Gazyva/Gazyvaro（obinutuzumab）治疗的患者在两年（104周）时实现完全缓解的人数显著更多，差异具有统计学意义且具临床意义。辉瑞小分子结直肠癌3期结果积极，将递交监管申请辉瑞（Pfizer）近日宣布，其关键性3期BREAKWATER研究中队列3取得积极顶线结果。该队列评估了Braftovi（encorafenib）与西妥昔单抗（商品名Erbitux）和mFOLFOX6治疗方案（包括氟尿嘧啶、亚叶酸钙和奥沙利铂）构成的组合疗法，用于既往未经治疗、携带BRAF V600E突变的转移性结直肠癌（mCRC）患者的疗效。百利天恒：自研ADC药物注射用BL-M11D1获批临床 3月4日，百利天恒（688506）发布公告，公司自主研发的创新生物药注射用BL-M11D1（CD33-ADC）的药物临床试验获得批准。BL-M11D1是与iza-bren出自同一技术平台、与iza-bren共享同一“连接子+毒素”平台的靶向CD33的ADC药物。珍宝岛药业拓展神经系统疾病产品管线，布瑞哌唑系列品种获批上市 3月11日，珍宝岛药业发布公告，子公司哈珍宝公司及鸡西分公司分别获得布瑞哌唑片及布瑞哌唑化学原料药的上市许可。这一成果标志着企业在抗精神病药物领域的布局迈出了关键一步，进一步丰富产品管线，提升了企业在神经系统疾病治疗领域的综合竞争力。全球唯一!康方生物三抗获批临床康方生物自主研发的注射用AK150正式获批临床，适应症为晚期实体瘤。根据公开信息，这是目前全球范围内唯一一款同时靶向LILRB1/LILRB2/CSF1R的在研三抗产品。正大天晴复方制剂1类新药获批临床正大天晴宣布其1类创新药TQB6457注射液在中国获批临床，用于治疗晚期恶性肿瘤。这是一款CCR8单克隆抗体与PD-1抗体组成的固定复方制剂，旨在通过探索以单一制剂代替联合用药，提升晚期肿瘤患者的用药依从性，打破用药限制。

2026-03-27

·投医问药

NEJM丨罗氏Atezolizumab联合化疗显著降低错配修复缺陷型结肠癌换着复发或死亡的风险

点击蓝字关注我们投医问药 Summary III期结肠癌患者即使接受标准辅助化疗，仍有约30%会发生复发。错配修复缺陷型结肠癌对氟尿嘧啶类药物具有内在耐药性，尽管已有研究表明免疫检查点抗体在转移性患者中显示优势，但术后辅助治疗中能否从抗PD-L1药物联合化疗中获益仍有待III期临床试验验证。 2026年3月26日，美国梅奥诊所、杜克大学及德国肿瘤学工作组的研究人员在《新英格兰医学杂志》发表题为"Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer"（Atezolizumab联合FOLFOX治疗III期错配修复缺陷型结肠癌）的研究论文。ATOMIC III期临床试验结果显示，在标准mFOLFOX6化疗基础上联合Atezolizumab治疗，使III期错配修复缺陷结肠癌患者的3年无病生存率从76.2%提升至86.3%，疾病复发或死亡风险降低50%，为这类患者的术后辅助治疗提供了新的标准方案。欢迎关注公众号/设置星标并下载原文 Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer.pdf 01 ｜INTRODUCTION 结直肠癌是全球第三大常见癌症和第二大癌症相关死因。证据表明，10%至15%的局限性结肠癌存在DNA错配修复缺陷，导致微卫星不稳定性高状态，其特征是高突变负荷、免疫检查点上调和丰富的预测新抗原。III期结肠癌患者的标准治疗是先行手术切除，然后接受氟尿嘧啶类药物联合奥沙利铂的辅助化疗。辅助治疗的目的是根除微转移灶，但仍有约30%的III期患者在治疗后出现复发。错配修复缺陷型结肠癌对氟尿嘧啶类药物具有内在耐药性，但对氟尿嘧啶联合奥沙利铂方案不显示耐药。在KEYNOTE-177试验中，针对包括微卫星不稳定性高肿瘤在内的转移性错配修复缺陷型结直肠癌患者，免疫检查点抗体Pembrolizumab被证明优于氟尿嘧啶类化疗。研究团队设计了ATOMIC III期试验，以研究在标准改良FOLFOX6化疗基础上联合Atezolizumab（一种抗PD-L1抗体）是否能延长可切除错配修复缺陷型III期结肠癌患者的无病生存期。Atezolizumab与PD-L1结合，阻止其与PD-1的结合，从而阻断抑制性信号，使细胞毒性T细胞能够攻击肿瘤细胞。 02 ｜RESULTS 该图展示了ATOMIC试验的患者流程图。共计712例患者按1:1比例随机分配至Atezolizumab联合改良FOLFOX6组（355例）或改良FOLFOX6单独治疗组（357例）。联合治疗组患者接受6个月Atezolizumab联合mFOLFOX6治疗，之后继续Atezolizumab单药治疗，总疗程12个月。对照组接受6个月mFOLFOX6单独治疗。试验在美国国家临床试验网络的303个研究中心和德国肿瘤学工作组的9个研究中心进行，涵盖社区诊所为主。图1. 患者注册、随机分组及随访流程该表展示了712例患者的基线特征。结果显示两组患者基线特征均衡：中位年龄64岁，55.1%为女性，53.9%为高风险患者（T4、N2或两者），65% ECOG体能状态评分0分，21.1%确诊林奇综合征。两组中位实验室确认错配修复缺陷型患者比例分别为91.3%和85.7%。表1. 患者的人口统计学和临床特征该图展示了主要终点分析结果。Kaplan-Meier生存曲线显示，中位随访40.9个月时，Atezolizumab联合mFOLFOX6组的3年无病生存率为86.3%（95%置信区间：81.8-89.8），而mFOLFOX6单独组为76.2%（95%置信区间：70.9-80.6）。疾病复发或死亡的风险比为0.50（95%置信区间：0.35-0.73），P<0.001，差异具有统计学意义。添加Atezolizumab使复发或死亡风险降低10个百分点，相对风险降低50%。图2. III期结肠癌患者的无病生存该图以森林图形式展示了预设亚组的无病生存分析结果。大多数亚组均显示Atezolizumab联合治疗的获益趋势。在接受超过6个周期（3个月）mFOLFOX6治疗的患者中，Atezolizumab显示出明显的无病生存获益（风险比0.41，95%置信区间：0.27-0.64），而在接受6个周期或更少mFOLFOX6治疗的患者中未观察到无病生存优势（风险比0.97，95%置信区间：0.44-2.11）。这些探索性发现表明，辅助Atezolizumab的治疗获益可能依赖于足够的化疗暴露量。图3. 无病生存的亚组分析该表详细记录了两组患者的安全性数据。结果显示，Atezolizumab联合mFOLFOX6组所有患者均发生不良事件，84.1%为3级或4级；mFOLFOX6单独组98.5%发生不良事件，71.9%为3级或4级。两组常见的3级及以上不良事件包括：中性粒细胞计数减少（43.6% vs 35.9%）、周围感觉神经病变（18.5% vs 15.0%）、腹泻（12.1% vs 8.4%）、疲劳（10.1% vs 3.3%）。免疫相关不良事件在联合治疗组更常见：高血糖（20.5% vs 10.2%）、甲状腺功能减退（19.9% vs 3.9%）、结肠炎（6.6% vs 0.6%）、斑丘疹（14.2% vs 6.0%），但多为1-2级。表2. 所有接受治疗患者按分级列出的选定不良事件 03 ｜DISCUSSION 该III期随机试验表明，在mFOLFOX6辅助化疗基础上联合Atezolizumab显著改善了可切除错配修复缺陷型III期结肠癌患者的无病生存，复发或死亡风险降低50%，且不良事件与已知的安全性特征一致。尽管观察到无病生存的显著改善，接受联合治疗的患者中仍有近14%在3年时出现复发或死亡，表明存在对PD-L1抗体的内在耐药。亚组分析提示，辅助Atezolizumab的治疗获益可能依赖于足够的化疗暴露量。该试验结果已被纳入最新的NCCN指南，支持对所有新诊断结肠癌患者进行普遍的错配修复状态检测，以识别Lynch综合征并确定免疫治疗的资格，为这类患者的精准治疗提供了重要依据。 References [1] Sinicrope FA, Ou FS, Arnold D, et al. Atezolizumab plus FOLFOX for Stage III Mismatch Repair–Deficient Colon Cancer. N Engl J Med. 2026;394(12):1151-1162. [2] André T, Shiu KK, Kim TW, et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 2020;383(23):2207-2218. [3] Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch repair deficiency. N Engl J Med. 2015;372(26):2509-2520. [4] Sargent DJ, Marsoni S, Monges G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol. 2010;28(20):3219-3226. [5] Overman MJ, Lonardi S, Wong KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. J Clin Oncol. 2018;36(8):773-779. [6] Taieb J, Shi Q, Pederson L, et al. Prognostic role of primary tumor sidedness and CMS in stage III colon cancer: pooled analysis of 3,634 patients from PETACC-8, ATLAS, IOAS, C-07, C-89822. Ann Oncol. 2022;33(5):530-540. [7] Loupakis F, Yang D, Yau L, et al. Primary tumor location as a prognostic and predictive marker in metastatic colorectal cancer. Nat Rev Clin Oncol. 2015;12(8):441-448. [8] Dienstmann R, Mason MJ, Sinicrope FA, et al. Prediction of overall survival in stage II and III colon cancer. J Clin Oncol. 2017;35(4):402-410. [9] Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378(13):1177-1188. [10] André T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant chemotherapy in locally advanced colon cancer. J Clin Oncol. 2009;27(19):3109-3116. [11] Allegra CJ, Yothers G, O'Connell MJ, et al. Bevacizumab in stage II-III colon cancer: 5-year update of NSABP C-08. J Natl Cancer Inst. 2013;105(1):21-34. 往期回顾【联合举办-清华大学生命科学学院行业大咖论坛】 ► 清华大学生命科学学院 “行业大咖讲坛”第一期晶泰科技赖力鹏 ► 清华大学生命科学学院 “行业大咖开讲”第二期迈威生物范梦奇【投医问药分享会】 ► 投医问药分享会第一期-脑转移肿瘤：基础科研、临床诊疗和成果转化（复旦大学迟喻丹；北医三院杨辰龙） ► 投医问药分享会第二期-细胞治疗（北京大学席建忠；北京科技研究院/海豚博士徐庞连；极客基因来威锋；清辉联诺马伟伟） ► 投医问药分享会第三期-AI+医药（晶泰科技赖力鹏；科迈生物黄小鲁；剂泰科技赖才达；数坤科技廖方舟；）【一文读懂系列】 ► Suzetrigine（镇痛/Nav1.8/VX-548） ► Efruxifermin（MASH/FGF21/Thrb） ► Penmenvy（/脑膜炎疫苗/MenABCWY） ► 全球首个iPS细胞疗法/日本干细胞监管政策【全球靶点在研管线一览】 ► CD3×BCMA×CD19► 双靶小核酸 ► GLP-1R×GIPR×GCGR ► TL1A单抗、双抗/多抗► miR-124 ► Kv7► ACVR2A/B ► amylin/AMYR► FGF21► Thr-β►VAP-1/SSAO►NTSR1 ► factor XI siRNA► GLP-1小分子激动剂►TRPC6 ► TfR & CD98hc 单靶/双靶透脑递送管线►GPNMB-RYK 【新靶点】 ► 癌症新靶点:eSrc；GSH/GGT；GPX1；OSBPL8；Gstm2/3；mSWI/SNF；ACOD1；ADRB2-CXCL16；GPX4；U2AF1；CD161；NNMT；RAS-PI3Kα； ► 代谢新靶点:CLCC1；RANK；SLC25A45；Or5v1/Olfr110； ► 皮肤新靶点:OXGR1；SLIT2-ROBO2-EID1-EP300； ► 自免新靶点:TRPV3–IL-6/CCL20–GC；HLA-DR15；MLKL； ► 心脏/血液新靶点:αIIbβ3；p38； ► CGT新靶点:OR7A10；KLHL6； ► 抗衰老新靶点:cGAS-STING；Nr3c2；HIS-71、DOT-1.3； ► 纤维化新靶点:ROCK2；GLIS3； ► 再生医学新靶点:FGF9； ► 神经精神类新靶点:TREM2；SCAN；CRL5^SOCS4；SLC45A1；SLC45A4； ► 避孕新靶点:STK33；投医问药投医问药起源于清华大学、北京大学和中国科学院，包含投医问药分享会和投医问药俱乐部，以及与清华大学生命科学学院合办的行业大咖论坛等板块，为生物医药领域专业人士专门打造，通过小型圆桌论坛和分享会的形式，提供一个深度交流和合作的平台。俱乐部成员包括PI、博士后、博士生以及生物医药产业和金融界的专业人士。在这里，大家可以分享自己的研究成果，讨论科研转化的可能性，寻找合作伙伴和资本介入的机会。投医问药注重建立信任关系，保持公益性，为生物医药相关人士促成各类资源的精准匹配，促进科研成果、创业想法的转化和社会价值的实现。欢迎关注投医问药，并添加小编微信号：seekmedicine，添加微信时请备注：单位/职业/姓名，如果是PI/教授、创始人、合伙人等，还请注明。声明：本内容仅用作生物医药行业信息传播，不构成任何用药和投资建议。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系seekmedicine@163.com。点赞收藏分享

100 项与亚叶酸钙相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D01211	亚叶酸钙	V03AF03	DB00650

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
转移性结直肠癌	美国	Avyxa Pharma	2026-02-03
脑叶酸转运不足引起的神经退行性变	美国	GSK Plc	2025-09-22
巨幼红细胞性贫血	巴西	Libbs Farmacêutica Ltda.	1999-06-22
结直肠癌	巴西	Libbs Farmacêutica Ltda.	1999-06-22
甲氨蝶呤中毒	巴西	Libbs Farmacêutica Ltda.	1999-06-22
药物中毒	日本	Pfizer Japan, Inc.	1963-01-11
贫血	美国	Hospira, Inc.	1952-06-20

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
III期结肠癌	临床3期	奥地利	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	比利时	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	埃及	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	法国	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	德国	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	意大利	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	葡萄牙	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	西班牙	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	瑞士	Pfizer Inc.	2001-01-01
III期结肠癌	临床3期	英国	Pfizer Inc.	2001-01-01

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临床结果

适应症

分期

评价

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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


NCT05567835 (TOGAR, CTgov)	临床2期	胃腺癌 \| 胃食管交界处腺癌	3	GSCF+leucovorin+Docetaxel+oxaliplatin+fluorouracil (Arm A: FLOT-TNT ( Investigational Arm))	鑰鬱構簾餘選獵憲淵築(醖艱鹹艱醖夢憲蓋願鏇) = 壓衊衊齋觸製蓋淵網製膚膚廠繭膚獵憲醖艱築 (築獵簾憲鏇積蓋廠鬱願, 構膚淵淵壓製衊顧遞淵 ~ 製艱襯選鹹鹹築鹹選願) 更多	-	2026-02-23
				GSCF+leucovorin+Docetaxel+oxaliplatin+fluorouracil (Arm B: FLOT-POP ( Standard Arm))	鑰鬱構簾餘選獵憲淵築(醖艱鹹艱醖夢憲蓋願鏇) = 壓製淵顧憲襯願範衊淵膚膚廠繭膚獵憲醖艱築 (築獵簾憲鏇積蓋廠鬱願, 獵製憲顧夢網築鏇遞醖 ~ 構艱鬱窪顧網鏇構選遞) 更多
NCT03785873 (BilT-03 \| BilT03, CTgov)	临床1/2期	晚期胆道癌	34	Nivolumab+leucovorin+Nanoliposomal-Irinotecan+5-fluorouracil	糧憲觸廠衊鑰構窪糧廠 = 鑰願鑰醖積願範築淵遞壓壓鹽鑰獵蓋鹹獵鏇鹹 (襯壓鹹鑰夢鹽醖醖製願, 膚襯齋築選醖醖網積齋 ~ 襯夢憲觸鬱顧襯鹽願廠) 更多	-	2026-02-13
NCT05047991 (Pubmed \| NEWS) 人工标引	临床2期	晚期胰腺腺癌	117	NALIRIFOX (liposomal irinotecan+ 5-FU+leucovorin+oxaliplatin)	遞築獵夢鹽簾衊繭醖顧(簾膚膚選鏇襯膚衊壓艱) = 糧壓淵鹽醖簾願襯鬱鬱願觸憲獵構築憲艱鹹餘 (選衊壓廠襯築選鑰鑰餘, 5.52 ~ 9.23) 更多	积极	2026-01-16
				gemcitabine + nab-paclitaxel	遞築獵夢鹽簾衊繭醖顧(簾膚膚選鏇襯膚衊壓艱) = 構淵積襯願艱廠鏇繭網願觸憲獵構築憲艱鹹餘 (選衊壓廠襯築選鑰鑰餘, 3.38 ~ 5.32) 更多
NCT04539808 (NeoOPTIMIZE, CTgov)	临床2期	胰腺腺癌 \| 胰腺导管腺癌	42	mFOLFIRINOX+nab-paclitaxel+leucovorin calcium+gemcitabine hydrochloride+potassium+losartan+Oxaliplatin+irinotecan hydrochloride+capecitabine+fluorouracil	壓衊餘壓鏇衊鑰願簾淵 = 鬱壓鬱餘艱獵壓壓糧廠蓋蓋獵顧醖廠膚獵獵夢 (餘觸壓選繭網積鬱糧觸, 範壓製壓廠齋繭鏇襯蓋 ~ 鏇製構廠廠襯鹹鬱鏇積) 更多	-	2026-01-14
NCT00136435 (CTgov)	临床2期	急性淋巴细胞白血病	100	L-asparaginase	廠簾艱醖鹹鹹範衊選膚 = 繭構衊網獵廠獵築築構餘鑰獵築遞網鏇憲鬱繭 (鹹憲蓋窪糧範壓簾構蓋, 構製廠簾壓衊鹹築鬱壓 ~ 觸艱壓鏇齋願膚夢餘糧) 更多	-	2025-10-20
NCT00878254 (CTgov)	临床2期	套细胞淋巴瘤	25	Mesna+Etoposide+Cyclophosphamide+Leucovorin+G-CSF+Doxorubicin+ifosfamide+Methotrexate+Rituximab+Vincristine+Cytarabine	遞淵餘夢齋齋獵築夢鏇(願糧範窪憲製鏇襯糧夢) = 範鹽膚築繭醖淵積齋遞獵餘憲餘鏇蓋襯壓齋鬱 (構艱積夢艱鏇齋鑰醖鏇, 築艱鹽艱鬱夢蓋鹽範憲 ~ 鬱淵製繭壓選鹽壓廠顧) 更多	-	2025-07-23
NCT04554836 (CTgov)	临床2期	直肠腺癌 \| RAS 突变结直肠癌 \| 结肠癌	6	Cetuximab+Leucovorin Calcium+Irinotecan Hydrochloride+Fluorouracil (FOLFIRI + Cetuximab)	觸蓋選夢廠膚鏇築艱選 = 憲遞鬱願顧築艱糧衊構鹽蓋鏇選齋夢齋遞艱鏇 (衊齋製鹽範醖繭築膚觸, 遞範憲襯窪餘夢窪鹽鏇 ~ 艱夢襯膚糧遞顧鏇鏇範) 更多	-	2025-06-08
				Leucovorin Calcium+Irinotecan Hydrochloride+Fluorouracil (FOLFIRI)	觸蓋選夢廠膚鏇築艱選 = 遞艱構築餘憲鹹鏇餘鑰鹽蓋鏇選齋夢齋遞艱鏇 (衊齋製鹽範醖繭築膚觸, 願願夢憲膚醖鏇獵築鑰 ~ 艱憲遞範衊淵鑰憲襯糧) 更多
NCT04937738 (PECORINO, Pubmed \| J Gastrointest Oncol)	临床3期	胃癌新辅助	69	FLOT (5-fluorouracil, leucovorin, oxaliplatin and docetaxel)	鏇遞艱壓積鑰構衊遞獵(壓憲網選艱築糧觸夢艱) = 鹽鹹壓遞觸鹹廠鹹廠淵艱衊簾醖觸壓鏇鹽繭築 (積構願觸製願齋淵淵襯, 31.9 ~ 65.6)	积极	2025-06-01
				XELOX (capecitabine and oxaliplatin)	鏇遞艱壓積鑰構衊遞獵(壓憲網選艱築糧觸夢艱) = 遞壓觸廠鏇鹹鏇獵淵遞艱衊簾醖觸壓鏇鹽繭築 (積構願觸製願齋淵淵襯, 8.9 ~ 39.8)
NCT02934529 (FIRE-4 (AIO-KRK-0114), Pubmed \| J Clin Oncol)	临床3期	转移性结直肠癌一线 \| 维持 RAS - \| BRAFV600E	-	FOLFIRI plus cetuximab	鏇鏇憲淵鏇顧壓齋蓋壓(憲顧齋觸糧鹹餘鏇窪醖) = 鏇蓋鹹積簾積鑰製遞齋糧鏇夢獵夢獵網網衊積 (網廠壓蓋願簾糧鹹醖壓 ) 更多	积极	2025-04-20
				FOLFIRI plus cetuximab followed by switch maintenance treatment using FU plus bevacizumab	鏇鏇憲淵鏇顧壓齋蓋壓(憲顧齋觸糧鹹餘鏇窪醖) = 醖糧範艱範繭醖鹹鹹艱糧鏇夢獵夢獵網網衊積 (網廠壓蓋願簾糧鹹醖壓 ) 更多
NCT04380337 (SHORT-FOX, CTgov)	临床2期	直肠癌 \| 直肠腺癌	38	IMRT+LEUCOVORIN CALCIUM+irinotecan+oxaliplatin+capecitabine+Fluorouracil	獵簾網夢鑰選鑰鏇網積 = 鑰鬱蓋鬱壓簾構願製壓網築獵醖構鏇鑰網繭觸 (淵鹹顧繭鏇鹽衊鏇遞構, 齋築鏇鹹範餘遞網選鏇 ~ 鹹構願鑰鬱顧艱遞遞齋) 更多	-	2025-02-25