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更新于：2025-07-08

Temozolomide

替莫唑胺

更新于：2025-07-08

概要

基本信息

药物类型

小分子化药

别名

3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-1,2,3,5-tetrazine-8-carboxamide、3,4-dihydro-3-methyl-4-oxoimidazo(5,1-d)-as-tetrazine-8-carboxamide、3-methyl-4-oxo-3,4-dihydroimidazo(5,1-d)(1,2,3,5)tetrazine-8-carboxamide

+ [27]

靶点

DNA

作用方式

抑制剂

作用机制

DNA抑制剂(DNA抑制剂)、DNA烷化剂

治疗领域

肿瘤神经系统疾病皮肤和肌肉骨骼疾病+ [10]

在研适应症

尤文肉瘤脑恶性胶质瘤转移性恶性黑色素瘤+ [85]

非在研适应症

听神经瘤伴有 11q23 异常的急性髓系白血病肾上腺嗜铬细胞瘤+ [96]

原研机构

Merck Sharp & Dohme Corp.

在研机构

Bristol Myers Squibb Co.

Novartis Pharmaceuticals Corp.

Alliance Foundation Trials LLC

+ [29]

非在研机构

Radiation Therapy Oncology Group

NYU Langone Health

Novartis AG

+ [39]

权益机构

Double Bond Pharmaceutical International AB

Institut Gustave Roussy EURL

Belarusian State University

+ [1]

最高研发阶段批准上市

首次获批日期

欧盟 (1999-01-26),

星形细胞瘤多形性胶质母细胞瘤胶质瘤

最高研发阶段(中国)批准上市

特殊审评加速批准 (美国)、孤儿药 (美国)、孤儿药 (欧盟)、优先审评 (中国)

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结构/序列

分子式C6H6N6O2

InChIKeyBPEGJWRSRHCHSN-UHFFFAOYSA-N

CAS号85622-93-1

关联

1,055

项与替莫唑胺相关的临床试验

NCT01777919

/ Not yet recruiting临床2期IIT

A PHASE II CLINICAL TRIAL FOR THE EVALUATION OF THE EFFICACY OF DISULFIRAM/COPPER COMBINATION AS AN ADJUVANT AND CONCURRENT CHEMOTHERAPY IN THE TREATMENT OF NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORM

Glioblastoma multiform (GBM) is the most common malignant primary brain tumor in adults. Despite maximal treatment tumor relapse occurs regularly accompanied by unfavourable prognosis. Among other reasons, it is believed that this could be in part due to the existence of the so-called tumor stem cells (TSCs), a cellular subfraction within GBM which escape therapy by being highly resistant to irradiation and chemotherapy and thus constituting the source of tumor recurrence.
GBM, like many other cancers, show a sub-population of aldehyde dehydrogenase (ALDH) overexpressing TSCs. More specifically, ALDH1A1, a cytoplasmatic isoform of ALDH, proved to be a novel stem cell marker in human GBM. In addition, ALDH1A1 has been shown to be a mediator for resistance of GBM to temozolomide (TMZ) and a reliable predictor of clinical outcome; prognosis of patients with a high level of ALDH1A1 expression was poor compared with that of patients with low levels. Consequently, ALDH1A1 may serve as a potential target to improve treatment of human GBM through inhibition of the enzyme.
Disulfiram (DSF) has been used for more than sixty years in the treatment of chronic alcoholism because of the unpleasant symptoms it provokes after ethanol intake. The underlying mechanism is believed to be the accumulation of acetaldehyde in the blood, due to inhibition of the liver ALDHs. Actually, DSF is a strong inhibitor of ALDH1A1 and relatively non-toxic at therapeutic (for chronic alcoholism) doses that can penetrate the blood-brain barrier. In addition, DSF has been shown to be cytotoxic on GBM stem-like cells, inhibiting the growth of TMZ resistant GBM cells and blocking self-renewal by
100% , while it has been identified as an inhibitor of human GBM stem cells in high-throughput chemical screens. Interestingly, a number of these actions were copper-dependent.
In the current Phase II clinical trial, DSF/copper combination will be tested as an adjunctive and concurrent chemotherapy in the treatment of newly diagnosed GBM. According to our hypothesis, initiation of DSF chemotherapy after the resection of the tumor and before the introduction of the standard radio-chemotherapy will inhibit ALDH1A1 of GBM TSCs making them more susceptible to radio-chemotherapy and possibly reducing the recurrence rate of GBM. On the other hand, the addition of copper will probably enhance the cytotoxic effects of DSF possibly through augmentation of its pro-apoptotic and proteasomal inhibitory actions.

开始日期2027-01-01

申办/合作机构

Universität Ulm

[+2]

NCT06816927

/ Not yet recruiting临床2期IIT

A Multi-Center, Randomized, Phase 2 Trial of Glioblastoma Immunotherapy Advancement With Nivolumab and Relatlimab (GIANT)

GIANT is an open-label, multi-center, randomized, perioperative (neoadjuvant followed by adjuvant), phase 2 trial with a safety lead-in phase to investigate the feasibility, safety and tolerability, and establish the biological activity of nivolumab with or without relatlimab in patients with isocitrate dehydrogenase (IDH) wildtype newly diagnosed glioblastoma (ndGBM).

开始日期2025-11-01

申办/合作机构

Duke University

NCT07015242

/ Not yet recruiting临床2期

The CAROLYN Trial: Lisocabtagene Maraleucelas First-Line Therapy for Primary Central Nervous System Lymphoma (PCNSL) in Transplant-Ineligible Patients

The purpose of this study is to evaluate the safety and efficacy of lisocabtagene maraleucel (Breyanzi/liso-cel/BMS-986387) in adults as first-line treatment in transplant-ineligible Primary Central Nervous System Lymphoma (PCNSL).

开始日期2025-09-30

申办/合作机构

Juno Therapeutics, Inc.

100 项与替莫唑胺相关的临床结果

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100 项与替莫唑胺相关的转化医学

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100 项与替莫唑胺相关的专利（医药）

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14,573

项与替莫唑胺相关的文献（医药）

2025-12-31·Human Vaccines & Immunotherapeutics

Trends in the immunotherapy for glioblastoma: A two-decade bibliometric analysis

Article

作者: Wang, Hongxin ; Yan, Wei ; Long, Zhi ; Yi, Zhenjie

Glioblastoma is a life-threatening primary malignant brain tumor with an unfavorable prognosis. Contributing factors to its poor outcome include tumor heterogeneity, low mutational burden, and immunosuppression within the tumor microenvironment. Recognizing these challenges, immunotherapeutic strategies have emerged as a promising avenue for glioblastoma treatment. Although several dynamic research and scientific trend have increasingly taken pace in the immunotherapeutic approaches to glioblastoma, systematic bibliometric studies on such trends are few. On this note, this study explores a bibliometric analysis of the research hotspots and trends in glioblastoma immunotherapy. We conducted a search in the Web of Science Core Collection database for articles on glioblastoma immunotherapy published between 2004 and 2024. Using VOSviewer and CiteSpace software, we analyzed collected articles to explore aspects such as country of origin, journal of publication, affiliated institute, authorship, keywords, and citation patterns. As of May 1, 2024, we retrieved 3,729 papers on Glioblastoma Immunotherapy. In the field of glioblastoma immunotherapy, the United States stands out as the leading contributor, with 1,708 publications and a substantial 90,590 citations. Following closely, China has made significant contributions through 926 publications, earning 17,533 citations, while Germany adds to the body of knowledge with 349 publications and 16,355 citations. Furthermore, Authoritative journals in this field include Clinical Cancer Research and Neuro-Oncology. The top five keywords during this period were temozolomide, radiotherapy, dendritic cell, cytotoxic T lymphocyte, and vaccination. Moreover, Hotspots in the field include immune checkpoint inhibitors and chimeric antigen receptor T cell therapy.

2025-12-31·Molecular & Cellular Oncology

TRIM22 promotes glioblastoma development by ubiquitinating Bcl-2

Article

作者: Zhang, Jiahao ; Cheng, Chao ; Huang, Jin ; Huang, Hui ; Chen, Yuning ; Liu, Yuankun ; Shao, Junfei ; Wang, Gaosong ; Jiao, Jiantong

Glioblastoma (GBM) exhibits elevated TRIM22 expression correlated with tumor progression, as validated in TCGA/GEO databases. The effects of TRIM22 knockdown and overexpression on GBM proliferation were evaluated with cellular assays. TRIM22 was identified as a potential Bcl-2 activator via a ubiquitination microarray. Flow cytometry (FCM) was utilized to investigate cell apoptosis. Additionally, the expression levels of Bcl-2 and proteins associated with Bcl-2 were evaluated using Western blot analysis. The interaction and ubiquitination of TRIM22 and Bcl-2 were analyzed via immunoprecipitation (IP). TRIM22 overexpression is correlated with glioma progression, and TRIM22 deficiency inhibits GBM cell proliferation. FCM revealed that TRIM22 knockdown promotes GBM cell apoptosis. A TRIM22-overexpressing ubiquitination microarray identified TRIM22 as a potential activator of Bcl-2. Western blot analysis revealed that TRIM22 increases the protein expression levels of Bcl-2. Ubiquitination assays revealed that TRIM22 promotes the stability of Bcl-2 via nondegradative ubiquitination. IP experiments indicated that TRIM22 binds to Bcl-2. TRIM22 may significantly impact glioma progression by modulating Bcl-2. Previous studies have shown that knockdown of TRIM22 can enhance the sensitivity of temozolomide treatment, so TRIM22 is expected to become a new target for glioma immunotherapy.

2025-12-31·NMC case report journal

Favorable Response to Conventional Chemoradiotherapy in Radiation-induced Glioma Harboring Coamplification of PDGFRA, KIT, and KDR: A Case Report and Literature Review

Article

作者: MIZUNO, Reina ; KANEKO-MISHIMA, Masayo ; TANIKAWA, Daisuke ; SAKAKIBARA, Ayaka ; HOMMA, Taku ; SUZUKI, Tomonari ; MISHIMA, Kazuhiko ; OZAWA, Tatsuya ; SAKURADA, Kokyo ; KATO, Shingo ; FUKUOKA, Masayoshi ; EHARA, Takuro ; SHIRAHATA, Mitsuaki

One of the most serious complications of cranial radiotherapy is the development of radiation-induced glioma, which is estimated to occur in 1%-4% of patients who have received cranial irradiation and has a worse prognosis than sporadic glioblastoma. Although comprehensive genetic analysis has recently uncovered the molecular characteristics of radiation-induced glioma, the full picture remains unclear due to its rarity. A 45-year-old man presented with generalized seizures caused by multiple brain tumors involving the right frontal lobe, thalamus, and brainstem. The patient had a history of whole-brain radiotherapy for recurrent Burkitt's lymphoma at the age of 12. He underwent craniotomy, and the histological diagnosis revealed a high-grade glioma with isocitrate dehydrogenase-wildtype, which was presumed to be a radiation-induced glioma that developed 33 years after whole-brain irradiation. Next-generation sequencing identified a CDKN2A/B deletion, as well as coamplification of several receptor tyrosine kinases-encoding genes, including PDGFRA, KIT, and KDR, all of which are located at 4q12. Amplification of this region is broadly observed across cancers and is associated with poor prognosis in sporadic glioblastoma. Nevertheless, the patient received chemoradiotherapy with temozolomide, followed by temozolomide maintenance therapy, resulting in a complete response of all lesions. Although radiation-induced gliomas are generally difficult to treat, our patient unexpectedly responded well to conventional chemoradiotherapy despite the coamplification of multiple receptor tyrosine kinases-encoding genes, which is typically suggestive of an aggressive phenotype. Our case indicates that some radiation-induced gliomas may have distinct molecular characteristics influencing the therapeutic response, which differ from those of sporadic glioblastomas.

666

项与替莫唑胺相关的新闻（医药）

2025-07-08

·今日头条

武汉协和完成全球首个体内CAR-T治疗！肺癌、脑瘤等多点破冰

2025年7月2日，武汉协和医院血液科团队在国际医学顶刊《柳叶刀（The Lancet）》发表了一项革命性研究，成为全球首个报道“体内制备CAR-T细胞治疗复发/难治多发性骨髓瘤”取得临床成功的研究。传统CAR-T疗法因制造流程复杂、物流要求严苛、等待周期长且成本高昂，其普及应用受到极大限制。而此次“体内制备CAR-T疗法”的突破具有里程碑意义，堪称血液肿瘤细胞治疗领域的重大进展——它不仅颠覆了传统的体外制备模式，更因操作简化、成本降低，有望大幅提升细胞疗法的可及性。这一突破性进展，正为全球无数肿瘤患者点亮希望之光，未来，更多生命将因此获得重生的机会，肿瘤治疗的新时代已悄然开启！ ▲截图源自“Lancet” 全球首例！武汉协和体内CAR-T疗法力克多发性骨髓瘤体内制备CAR-T疗法的核心机制，是将CAR转基因直接递送至患者体内的内源性T细胞，在原位将其重编程为CAR-T细胞。作为“即用型产品”而非定制药物，它省去了血液分离、CAR-T细胞体外制造及淋巴细胞清除等环节。 ESO-T01是实现该疗法的关键载体，这是一种靶向纳米抗体的免疫屏蔽慢病毒载体，含有人源化抗B细胞成熟抗原（BCMA）单域抗体嵌合抗原受体（CAR），专门用于体内T细胞工程改造，且已在临床前研究中展现出良好的安全性和有效性。武汉协和医院血液科团队在《柳叶刀》发表的研究，正是基于该载体的体内制备CAR-T疗法，针对复发或难治性多发性骨髓瘤患者开展的首次人体试验（NCT06691685）数据，此次公布了4例接受最低剂量治疗患者的结果，这些年龄入组患者18岁，确诊表达BCMA的多发性骨髓瘤，既往接受过至少两种疗法且病情进展，对免疫调节剂和蛋白酶体抑制剂耐药，同时存在可测量的病变。接受ESO-T01治疗后疗效显著。结果显示：患者1在治疗第2个月达到严格意义上的完全缓解，所有髓内和髓外病变均消退（详见下图B）。 ▲图源“Lancet”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除患者2在第28天达到严格完全缓解，病变完全消退（详见下图D）。 ▲图源“Lancet”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除患者3和4达到部分缓解（PR），至第28天肿瘤病变缩小，骨髓中微小残留病灶转阴（详见下图E、F）。 ▲图源“Lancet”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 CARv3-TEAM-E疗法：助3例复发性胶质母细胞瘤患者肿瘤快速消退胶质母细胞瘤是成人中最常见的原发性恶性脑肿瘤，极具侵袭性，因生长快速、部位特殊，肿瘤易扩散到周围脑组织，几乎无法完全手术切除，即便看似根除，也极易复发，治疗难度极大。据统计，95%的患者在确诊后五年内死亡，复发患者通常在6~8个月内离世。因此，迫切需要寻求新的治疗方法。近期，全球知名医学期刊《新英格兰医学杂志》报道了“CARv3-TEAM-ET细胞[经过基因工程改造的嵌合抗原受体T细胞，能通过分泌T细胞衔接抗体分子（TEAM），靶向野生型EGFR蛋白、表皮生长因子受体变体III（EGFRvIII）肿瘤特异性抗原]，治疗复发性胶质母细胞瘤”的惊艳案例（NCT05660369），给众多患者带来了新希望！三名复发性胶质母细胞瘤患者接受了这种细胞治疗，放射影像学显示，在单次脑室内输注后数天内，肿瘤就出现了迅速且显著的消退。患者1因头痛和意识混乱就诊，影像学检查发现左岛叶有一强化肿块，接受开颅手术后确诊为胶质母细胞瘤，肿瘤EGFRvIII阳性。在接受标准治疗（放疗、替莫唑胺化疗）后，疾病复发，最终确诊为EGFRvIII阳性的复发性肿瘤，遂入组接受CARv3-TEAM-E输注。结果显示：在CARv3-TEAM-E输注前6天（第-6天）的间隔MRI扫描显示，肿瘤仍在活跃进展。而第一次输注CAR-T细胞1天后，MRI扫描显示，肿瘤迅速消退（详见下图），且这种放射学改善在接下来2周的后续MRI扫描中得到证实。 ▲图源“N Engl J Med”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除患者2是一位72岁男性，因阅读困难就诊，MRI检查发现左侧颞叶后部有一个增强肿块。接受开颅手术和肿瘤切除术后，确诊为EGFRvIII阳性胶质母细胞瘤，IDH（异柠檬酸脱氢酶）野生型且MGMT甲基化。既往接受了标准放射治疗、替莫唑胺化疗、肿瘤治疗野治疗，但初次诊断20个月后，监测影像显示肿瘤进展，再次进行病理确诊为EGFRvIII阳性复发性胶质母细胞瘤。该患者遂入组，并通过脑室内导管单次输注了CARv3-TEAM-ET细胞。结果显示：治疗第2天的MRI检查提升，肿瘤横截面积减少18.5% ，第69天时较输注前基线值进一步减少60.7% 。在未接受糖皮质激素或抗血管生成治疗的情况下，这种反应持续改善，且在最后一次评估时（单次输注后超过150天）仍然持久（详见下图）。对脑脊液样本的细胞外囊泡RNA进行纵向液体活检显示，EGFRvIII和EGFR拷贝数随时间推移而减少，在治疗后样本中拷贝数仍低于检测阈值。 ▲图源“N Engl J Med”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除患者3是一位57岁女性，因数周的词汇困难和癫痫发作而就诊，MRI检查发现左顶叶增强肿块。接受开颅手术和肿瘤切除术后，病理分析证实为胶质母细胞瘤，IDH野生型，MGMT未甲基化，肿瘤EGFRvIII表达阳性且EGFR拷贝数增加。随后接受了放射治疗+替莫唑胺化疗，因出现血小板减少，化疗剂量减少。确诊6个月后，间期影像学检查显示肿瘤复发，遂入组该研究，再次接受开颅手术进行开放活检并植入Ommaya储液器，复发手术时的组织分析显示EGFRvIII表达缺失。入组后，她通过脑室内导管接受了CARv3-TEAM-ET细胞治疗。结果显示：CAR-T输注前MRI再次显示广泛的复发性疾病负担（图3C），而在输注后第5天MRI扫描显示，肿瘤几乎完全消退（详见下图）。治疗后脑脊液样本中提取的细胞外囊泡RNA在个别时间点显示EGFRvIII和EGFR的拷贝数较低，后来变得无法检测到。 ▲图源“N Engl J Med”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除我国自研CEA CAR-T疗法亮相ASCO大会，实体瘤（结直肠癌、胃癌、非小细胞肺癌、胆道肿瘤）疾病控制率高达88% ASCO大会报道了我国自研新型CAR-T细胞疗法——CEA CAR-T治疗实体瘤的I期临床试验（NCT05396300）振奋数据。该研究共纳入40例标准疗法失败的实体瘤患者，包括35例结直肠癌（CRC）、3例胃癌（GC）、1例非小细胞肺癌（NSCLC）、1例胆道肿瘤（BTC）患者，将入组患者分为两组，即腹腔注射组（IP组，16例）、静脉输注组（IV组，24例）。结果显示：疾病控制率（DCR）IP组达88% （14/16），显著优于IV组的67% （16/24）。此外， IP组客观缓解率（ORR）为25% （4/16），高于IV组的8% （2/24）。值得关注的是， IP输注高剂量组ORR提升至28.5% ，且所有应答患者的肿瘤缓解期均超过5个月，其中 1例患者在6个月随访时靶病灶消退率达76% 。综上，CEA CAR-T细胞疗法经腹腔注射或静脉输注后毒性可控，其中腹腔注射疗法抗肿瘤潜力突出，高剂量组更能延长肿瘤缓解期。再传捷报！我国另一款自研Claudin18.2 CAR-T疗法，助胰腺癌患者8个月未复发除了这款国研CEA CAR-T疗法外，我国还有一款自研的靶向Claudin18.2的CAR-T疗法，《免疫前沿》杂志报道了这款Claudin18.2 CAR-T治疗胰腺癌，获得完全缓解的振奋案例。该患者是一位72岁男性，确诊Ⅲ期胰腺导管腺癌（pT2N2M0，Ⅲ期），曾接受过胰十二指肠切除术、吉西他滨联合卡培他滨辅助化疗、FOLFIRINOX方案等等多线治疗，但病情仍持续进展，并出现肝/腹膜转移、颈部淋巴结转移等，后因严重不良反应被迫终止治疗。遂入组入组 Claudin18.2 CAR-T 疗法临床试验（NCT05620732），接受单次细胞输注。结果显示：患者在CAR-T细胞输注1个月后即达到完全缓解（CR），肿瘤标志物CA19-9从1100U/mL显著降至25.85U/mL ，恢复到正常范围（详见下图），且 CA19-9在治疗5个月后仍保持正常水平。此外，PET-CT扫描显示颈部淋巴结、肺部及其他转移病灶完全消失，且 CAR-T细胞治疗后8个月，颈部及肺部病灶未复发 (详见下图)。 ▲图源“Front Immunol”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除小编寄语时至今日，CAR-T 细胞疗法在血液系统恶性肿瘤的治疗领域已取得突破性进展，众多患者从中受益。令人欣慰的是，近年来全球的研究人员从未停止探索的脚步，持续钻研各种新型策略，致力于降低肿瘤抗原异质性，打破免疫抑制的困境，并在胃癌、脑瘤、胰腺癌、肝癌、结直肠癌等实体瘤领域取得了突破性进展！全球肿瘤医学部小编也期望随着越来越多明星靶点的涌现、技术的不断革新，CAR-T疗法可以早日突破价格和癌症治疗的瓶颈，造福更多的癌症晚期患者！参考资料 [1]Xu J,et al.In-vivo B-cell maturation antigen CAR T-cell therapy for relapsed or refractory multiple myeloma[J]. The Lancet, 2025. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01030-X/fulltext [2]Choi B D,et al.Intraventricular CARv3-TEAM-E T cells in recurrent glioblastoma[J]. New England Journal of Medicine, 2024, 390(14): 1290-1298. https://www.nejm.org/doi/full/10.1056/NEJMoa2314390 [3]Zhang H,et al.Phase I trial of hypoxia-responsive CEA CAR-T cell therapy in patients with heavily pretreated solid tumor via intraperitoneal or intravenous transfusion[J]. 2024. https://www.asco.org/abstracts-presentations/ABSTRACT443682 [4]Zhong G,et al.Complete remission of advanced pancreatic cancer induced by claudin18.2-targeted CAR-T cell therapy: a case report. Front Immunol. 2024 Feb 29;15:1325860. https://pmc.ncbi.nlm.nih.gov/articles/PMC10937427/ 本文为全球肿瘤医生网原创，未经授权严禁转载

免疫疗法细胞疗法

2025-07-07

·PRNewswire

Belay Diagnostics Announces the Validation of Vantage™ Assay for Evaluation of MGMT Promoter Methylation in Cerebrospinal Fluid

Validation Data on 60 Patients published in Cancer Genetics CHICAGO, July 7, 2025 /PRNewswire/ -- Belay Diagnostics, a CLIA/CAP accredited laboratory focused on the development and commercialization of molecular diagnostics targeting central nervous system (CNS) cancers, announced the results of the analytical validation study of the Belay Vantage™ assay for detection of MGMT (Methylation of the O6-methylguanine-DNA methyl-transferase) promoter methylation in cerebrospinal fluid (CSF) for primary and metastatic CNS cancers as reported in Cancer Genetics. The assay uses quantitative polymerase chain reaction (qPCR) on DNA extracted from CSF and has an analytical sensitivity of 95.5% and specificity of 100%. . MGMT promoter methylation testing is recommended in all high-grade gliomas. MGMT is one of the strongest prognostic and predictive biomarkers in glioblastoma, an aggressive cancer with a prognosis of six months or less that accounts for nearly 50% of all primary brain malignancies. Positive MGMT status is associated with a more favorable response to alkylating chemotherapies such as Temozolomide (TMZ). The Belay Vantage™ assay evaluates MGMT promoter methylation status through innovative and minimally invasive sampling of CSF for individuals with known or suspected CNS tumors using low input DNA (5 ng). This represents a distinct advantage over the current method of MGMT testing where invasive biopsy or resection is used to obtain patient samples and 40–250 ng of vital CNS tissue is required. Importantly, the study demonstrates the use of just 2–3 ml of CSF, significantly less than that used by standard of care cytology and flow cytometry, enabling easy implementation into existing clinical workflows. Vantage is the first to use an enzymatic conversion method that maintains integrity of the patient's DNA and minimizes degradation, thereby increasing ability to process DNA downstream, improving accuracy. In contrast, currently available commercial tests use bisulfite conversion that cause DNA damage. The novelty of performing this assay directly from CSF versus tissue facilitates a rapid 3-day turnaround. When ordered with Summit™, Belay's pioneering CSF-based tumor-derived genomic profiling assay for patients with CNS cancer, the turnaround is 7–10-days. "We are grateful to have the opportunity to bring novel and essential testing such as Vantage and Summit to clinicians in order to serve patients with these conditions. I am appreciative of our team members at Belay and Johns Hopkins University who work diligently in providing innovative solutions to inform diagnosis and management of brain cancer," said Brian Coe, Co-founder and Chief Executive Officer of Belay Diagnostics. About Belay Diagnostics Belay Diagnostics is focused on pioneering diagnostic technologies that transform the CNS cancer journey. Belay's Summit™ and Vantage™ advanced liquid biopsy tests in CSF provide molecular characterization that can markedly enhance diagnostic accuracy, tumor classification, predictive prognosis, therapeutic actionability and clinical trial options for those with CNS tumors and malignancies. Our mission is to serve patients and those who care for them. Together, we can help patients with CNS tumors find a path forward. Belay Diagnostics | Brain & Spinal Cord Cancer Testing SOURCE Belay Diagnostics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2025-07-07

·ioncology

2025 BOC/BOA丨陈誉教授：新型免疫治疗及联合策略在围术期和晚期治疗中的应用与展望

点击上方蓝字关注我们编者按：2025年中国临床肿瘤学会年度进展研讨会（BOC）暨Best of ASCO® 2025 China（BOC/BOA）于2025年7月4—6日在古都南京成功举行。在黑色素瘤专场，CSCO专家汇报了国内外黑色素瘤的最新研究进展，围绕早期新辅助、辅助免疫治疗和晚期双抗体治疗、细胞治疗等前沿热点展开深入讨论。本文基于福建省肿瘤医院陈誉教授的报告，对黑色素瘤围手术期免疫治疗策略和晚期新型治疗策略的探索进行总结。黑色素瘤围术期治疗概览黑色素瘤是一类侵袭性较强的恶性疾病，早期可切除患者术后仍面临一定的复发风险，围术期系统治疗除了有助于缩瘤降期以外，也是降低术后复发、改善远期生存的重要治疗手段。KEYNOTE054、CheckMate238、KEYNOTE716、CheckMate76K等研究已经证实了PD-（L）1免疫检查点抑制剂辅助治疗的RFS生存获益，奠定了免疫单药辅助治疗的标准。在此基础上，更加强化的免疫联合治疗是否能进一步提升疗效？2025年ASCO大会报道的3期RELATIVITY-098研究，抗PD-1联合抗LAG-3（纳武利尤单抗＋Relatlimab）辅助治疗并未能相较单免治疗显著改善RFS（HR 1.01）。无独有偶，抗PD-1联合抗TIGIT（帕博利珠单抗＋Vibostolimab）的3期KEYVIBE-010研究也与去年宣布失败，为“免疫plus”辅助治疗蒙上一层阴影。在以辅助免疫联合治疗为主的围术期“加法”受阻时，新辅助免疫治疗为黑色素瘤围术期治疗“加法”开辟了新路径。从理论上来看，未切除肿瘤具有较高的肿瘤新抗原以及丰富的肿瘤浸润性淋巴细胞，而且保留较为完整的肿瘤淋巴系统，因此能够相较于已切除肿瘤产生更强烈的免疫治疗效果。SWOG1801、NADINA研究证实了新辅助±辅助免疫治疗的模式能够进一步改善患者预后，而国际新辅助黑色素瘤联盟（INMC）的大型汇总分析也表明了新辅助治疗的获益，达到pCR的患者能够转化为更高的RFS率。皮肤型黑色素瘤围术期治疗上述KEYNOTE054、CheckMate238、KEYNOTE716、CheckMate76K研究均为欧美国家主导的全球多中心研究，纳入患者以皮肤型黑色素瘤为主，单免疫仍是当前辅助免疫治疗标准，但免疫联合治疗的获益仍有待观察。新辅助免疫治疗的加入是有潜力的围术期免疫“加法”策略。2025年ASCO大会报道了一项多中心、单臂2期研究，将帕博利珠单抗用于IIB/C期患者，可相较于历史对照显著降低IIc期患者的前哨活检（SLN）阳性率（16.7% vs 40%），且耐受性好，没有患者发生肿瘤进展导致不可切除或者毒性延迟手术。此次ASCO大会上，还报道了多项新辅助免疫联合治疗的初期研究，如EA6194研究显示帕博利珠单抗＋Vidutolimod（抗PD-1＋TLR9激动剂）新辅助治疗IIIB-D期患者，主要病理缓解（MRP）率达79%；NeoACTIVATE研究显示阿替利珠单抗＋Tiragolumab（抗PD-L1＋TIGIT）用于III期患者的MRP率为47.1%。肢端和黏膜型黑色素瘤围术期治疗肢端和黏膜型黑色素瘤在西方人群中较为罕见，在亚洲及中国患者中更加多见。中国研究者为这些类型黑色素瘤的围术期治疗探索贡献了重要的循证医学证据。如2024年底，北京大学肿瘤医院团队发表于STTT的一项Ib期研究显示，特瑞普利单抗联合溶瘤病毒疗法取得了77.8%的病理学缓解率和33.3%的MRP率。此次ASCO大会上，该团队报道了另一项CAP 03-NEO研究显示，卡瑞利珠单抗＋阿帕替尼＋替莫唑胺的“免靶化”三药方案用于可切除II/III期肢端黑色素瘤新辅助治疗，也展现了积极的疗效和安全性，病理缓解率为53.3%，pCR率达23.3%；经新辅助治疗后获得pCR或MPR的患者，其12个月RFS率为100%。且治疗耐受性良好，≥3级TEAEs发生率为36.7%，导致停药的TEAEs发生率为13.3%。最常见不良事件为白细胞减少、肝功能异常，没有5级不良事件发生。以双抗为基础的晚期免疫和细胞治疗双靶点的单克隆抗体是近2年及未来的另一大创新药物研发热点，包括ADC和ICI均可进行双抗研发升级。2025年ASCO大会上，郭军教授在口头报告中汇报的一项1/2期研究，采用的是一种首创新药PD-1/IL-2α偏向双抗（IBI363）。肿瘤特异性T细胞（TSTs）可共表达 PD-1和IL-2Rα。IBI363是首创α偏向型设计，能够增强抗肿瘤效果且最大化避免外周毒性。在 I 期研究（CIBI363A102）及一项治疗黑色素瘤的2期研究（CIBI363A201）中，ORR和DCR分别达23.3%和76.7%，中位PFS为5.7个月，高于既往研究报道数据（不足3个月）；中位OS达14.8个月。在52 例未接受过免疫治疗的肢端型和黏膜型患者中，未确认ORR达63.5%，待确认ORR达75%。基于这些积极结果，该治疗药物已经被中国CDE纳入突破性治疗，被FDA授予快速通道资格认定。在细胞治疗方面，Lifileucel是一种个性化的一次性肿瘤衍生自体T细胞免疫疗法，国际上已被批准用于PD-1免疫经治的晚期黑色素瘤成年患者。此次ASCO大会报道的C-144-01是一项2期多中心开放性研究，在既往中位治疗3线的情况下，Lifileucel的ORR达31.4%，长期随访显示5年OS率达19.7%。北京大学肿瘤医院团队此次ASCO大会报道的一项1期研究，使用单独肿瘤浸润性淋巴细胞（TIL）治疗亚洲黑色素瘤患者，ORR为41.7%，在特定剂量亚组中的DCR达到 100%，治随访是PFS尚未达到。总结和展望围术期治疗“免疫plus”是近年来的研究热点，但所获结果差异较大，辅助免疫联合治疗受阻，而新辅助免疫治疗且获得病理缓解的患者有望转化为更好的生存获益。围术期治疗的获益究竟来自新辅助还是辅助治疗阶段，美国FDA认为“越来越需要替代性的试验设计来评估新药在围手术期治疗方案每个治疗阶段的疗效”。潜在的试验设计可能包括多臂试验（例如，有超过两个治疗组的随机试验）或包含重新随机分配的试验（例如，SMART序贯多重分配随机试验设计）。在晚期治疗领域，双抗类药物以及新型细胞疗法展现了积极的抗肿瘤活性和可控的安全性，未来值得进一步扩大样本研究，为患者提供更优治疗证据。参考文献上下滑动查看更多内容[1]Rutkowski P, Mandala M. Perioperative therapy of melanoma: Adjuvant or neoadjuvant treatment. Eur J Surg Oncol. 2024;50(3):107969. doi:10.1016/j.ejso.2024.107969[2]Nivolumab plus relatlimab vs nivolumab alone for the adjuvant treatment of completely resected stage III–IV melanoma: Primary results from RELATIVITY-098.ASCO 2025[3]Neoadjuvant-adjuvant pembrolizumab in clinical stage IIB/C melanoma.ASCO 2025[4]A phase II randomized study of neoadjuvant pembrolizumab (P) alone or in combination with vidutolimod (V) in high-risk resectable melanoma: ECOG-ACRIN EA6194.ASCO 2025[5]NeoACTIVATE arm C: Phase II trial of neoadjuvant atezolizumab and tiragolumab for high-risk operable stage III melanoma.ASCO 2025[6]Liu, J., Wang, X., Li, Z. et al. Neoadjuvant oncolytic virus orienx010 and toripalimab in resectable acral melanoma: a phase Ib trial. Sig Transduct Target Ther　9, 318 (2024). https://doi.org/10.1038/s41392-024-02029-2[7]Neoadjuvant camrelizumab plus apatinib and temozolomide for resectable stage II/III acral melanoma: The CAP 03-NEO trial.ASCO 2025[8]Efficacy and safety results of a first-in-class PD-1/IL-2α-bias bispecific antibody fusion protein IBI363 in patients (pts) with immunotherapy-treated, advanced acral and mucosal melanoma.ASCO 2025[9]Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study.ASCO 2025[10]Influence of tumor infiltrating lymphocytes (TIL) monotherapy on persistent clinical and immunological responses in Asian metastatic melanoma patients with specific CD8+ TIL proportions: A phase I trial.ASCO 2025陈誉教授福建省肿瘤医院肿瘤学博士、主任医师、博士研究生导师、博士后导师福建省肿瘤医院党委委员副院长福建医科大学肿瘤临床医学院副院长，内科学教研室主任福建省五四青年奖章获得者中华医学会肿瘤学分会肿瘤内科专家委员会委员中国临床肿瘤学会理事中国临床肿瘤学会黑色素瘤专家委员会副主任委员中国临床肿瘤学会免疫治疗专家委员会常务委员中国抗癌协会第一/二届青年理事会常务理事中国抗癌协会多原发和不明原发性肿瘤专业委员会常务委员福建省抗癌协会第一届黑色素瘤专业委员会主任委员福建省肿瘤质控中心黑色素瘤质控专家组组长福建省抗癌协会第二届肿瘤内科专业委员会副主任委员国家卫健委2022年《黑色素瘤诊疗指南》、2018-2024年《CSCO黑色素瘤诊疗指南》、2019-2024《CSCO尿路上皮癌诊疗指南》、《CSCO原发性肝癌诊疗指南》执笔人，国家卫健委黑色素瘤单病种质控专家，福建省高层次人才，第一完成人获得福建省科技进步二等奖一项（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

ASCO会议临床结果免疫疗法临床3期临床2期

100 项与替莫唑胺相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06067	替莫唑胺	L01AX03	DB00853

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
尤文肉瘤	日本	Ohara Pharmaceutical Co., Ltd.	2019-02-21
尤文肉瘤	日本	MSD KK	2019-02-21
脑恶性胶质瘤	欧盟	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	冰岛	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	列支敦士登	Teva Pharmaceuticals Europe BV	2010-01-28
脑恶性胶质瘤	挪威	Teva Pharmaceuticals Europe BV	2010-01-28
转移性恶性黑色素瘤	澳大利亚	Merck Sharp & Dohme (Australia) Pty Ltd.	2009-11-13
胶质母细胞瘤	中国	江苏天士力帝益药业有限公司	2004-04-30
星形细胞瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
星形细胞瘤	挪威	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
多形性胶质母细胞瘤	挪威	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	欧盟	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	冰岛	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	列支敦士登	Merck Sharp & Dohme BV	1999-01-26
胶质瘤	挪威	Merck Sharp & Dohme BV	1999-01-26

未上市

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
神经母细胞瘤	申请上市	欧盟	ORPHELIA Pharma SAS	2024-11-14
子宫平滑肌肉瘤	临床3期	美国	Alliance for Clinical Trials in Oncology	2022-03-30
脑干胶质瘤	临床3期	美国	National Cancer Institute	2011-01-26
脑干胶质瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
成人脑星形细胞瘤	临床3期	美国	National Cancer Institute	2011-01-26
成人脑星形细胞瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
高级别胶质瘤	临床3期	美国	National Cancer Institute	2011-01-26
高级别胶质瘤	临床3期	加拿大	National Cancer Institute	2011-01-26
小儿小脑星形细胞瘤	临床3期	美国	National Cancer Institute	2011-01-26
小儿小脑星形细胞瘤	临床3期	加拿大	National Cancer Institute	2011-01-26

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临床结果

适应症

分期

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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


NCT04574856 (Phase 2 Study of Multiparametric Magnetic Resonance Imaging-Guided High-Dose Response-Adaptive Radiation Therapy With Concurrent Temozolomide in Patients With Newly Diagnosed Glioblastoma, Pubmed \| Int J Radiat Oncol Biol Phys)	临床2期	胶质母细胞瘤	30	Temozolomide (Patients with newly diagnosed GBM)	窪鏇鏇淵艱齋鏇顧鏇積(鏇簾範艱選鏇鹹選糧窪) = 選鏇壓鬱鹹廠獵鬱遞醖鏇願範願簾窪齋糧範獵 (鑰齋壓簾範餘鏇襯積鬱 ) 更多	积极	2025-07-01
NCT00629343 (CTgov)	临床1期	恶性间皮瘤 \| 软组织肉瘤	27	Temozolomide+Azacitidine	齋鑰窪獵築築顧餘構壓 = 憲構蓋鏇選獵糧窪糧遞艱遞襯鑰積顧夢築獵蓋 (夢願製積衊壓觸襯醖鬱, 繭積選壓鏇顧選觸選壓 ~ 鬱壓淵選艱壓鑰製觸鬱) 更多	-	2025-06-05
ASCO2025	临床2期	高风险神经母细胞瘤	34	HITS (Irinotecan, Temozolomide, Naxitamab, GM-CSF)	齋觸選觸網鏇繭顧遞觸(繭顧齋簾鹽遞觸鑰鹽鹽) = 膚糧繭選襯範夢艱簾鹹餘醖膚築顧遞範鏇鹽顧 (繭積鹹範蓋積鏇鹽憲壓 ) 更多	积极	2025-05-30
				NICE (Naxitamab, GM-CSF, Ifosfamide, Carboplatin, Etoposide)	齋觸選觸網鏇繭顧遞觸(繭顧齋簾鹽遞觸鑰鹽鹽) = 鏇網鬱簾夢憲鏇衊鏇窪餘醖膚築顧遞範鏇鹽顧 (繭積鹹範蓋積鏇鹽憲壓 ) 更多
NCT04280848 (Phase II study of UCPVax in newly diagnosed glioblastoma, ASCO2025)	临床2期	胶质母细胞瘤辅助 non-mutated IDH1 \| unmethylated MGMT status	-	UCPVax + Temozolomide	壓襯製糧夢遞繭製廠獵(糧顧構顧觸廠鏇簾壓糧) = 淵鏇築蓋製築壓鏇網鹽遞築積夢製襯鏇願鬱鏇 (襯積糧衊齋鏇鹹壓窪襯 ) 更多	积极	2025-05-30
NCT02761070 (JCOG1308C, ASCO2025)	临床3期	复发性胶质母细胞瘤	146	Bevacizumab	簾蓋衊遞糧製觸網襯範(淵淵醖網廠壓鑰壓糧選) = 19.4% in arm A 艱壓鏇膚糧選構範膚範 (膚顧遞鏇鹽簾願醖簾糧 ) 更多	不佳	2025-05-30
				Dose-dense Temozolomide
NCT00626990 (CATNON, ASCO2025)	临床3期	胶质瘤辅助 IDH mutation \| total copy number alterations \| methylation subtype	751	Radiotherapy alone	觸鹽鹹窪糧鹽壓壓鏇夢(襯遞鹽鏇築顧願選夢鏇) = 8.5 years 糧淵壓鹹獵齋鑰選廠顧 (蓋憲齋衊願艱鏇艱鑰繭 ) 更多	积极	2025-05-30
				Concurrent Temozolomide
BT008 (ASCO2025)	临床1/2期	高级别胶质瘤辅助	34	temozolomideTMZde (MB-FUS+TMZ)	壓遞觸襯積憲構壓積繭(廠鑰餘簾選艱鬱齋顧餘) = No serious procedure-related AEs were seen, with the most common AEs being mild, self-resolving 積顧醖獵鏇襯夢願憲顧 (遞鬱窪壓製鹹醖獵糧齋 ) 更多	积极	2025-05-30
				temozolomide (External cohort)
ASCO2025	N/A	-	159	temozolomide (Pancreatic NETs (PNETs))	憲鹹糧簾鹽淵繭築觸鏇(積鏇憲憲壓廠鹽顧簾餘) = 鬱鑰淵鬱鹽醖鬱艱餘衊範憲廠願鏇襯構夢觸壓 (膚願簾廠網鑰齋鑰鏇獵 ) 更多	积极	2025-05-30
				temozolomide (Gastrointestinal NETs (GINETs))	憲鹹糧簾鹽淵繭築觸鏇(積鏇憲憲壓廠鹽顧簾餘) = 憲鬱網糧繭衊窪鏇鑰夢範憲廠願鏇襯構夢觸壓 (膚願簾廠網鑰齋鑰鏇獵 ) 更多
ASCO2025	N/A	平滑肌肉瘤维持	20	Doxorubicin plus dacarbazine	鹹蓋觸齋鏇網鏇築窪簾(衊構糧糧範構齋網願窪) = 淵製壓憲願夢積膚窪繭鑰鹹獵製廠齋糧顧積鏇 (鏇廠簾齋觸蓋膚鬱廠憲 )	积极	2025-05-30
NCT03554473 (CTgov)	临床1/2期	复发性小细胞肺癌 \| 小细胞癌 \| 小肠癌复发	37	Epinephrine+CT scan+Acetaminophen+Temozolomide+Dexamethasone+M7824+Diphenhydramine (Arm A/M7824 (MSB0011359C) Monotherapy)	衊獵網遞鹽憲獵遞鑰夢 = 構顧壓範顧廠願築廠壓製壓遞獵淵窪願構顧簾 (選廠壓衊醖構淵膚範餘, 鬱餘壓襯夢艱廠醖鹽製 ~ 襯憲淵選淵鬱夢糧蓋鑰) 更多	-	2025-05-09
				Epinephrine+CT scan+Acetaminophen+Dexamethasone+M7824+Diphenhydramine+Topotecan (Arm B/M7824 (MSB0011359C) Plus Topotecan)	衊獵網遞鹽憲獵遞鑰夢 = 襯衊襯鬱齋簾選餘觸鏇製壓遞獵淵窪願構顧簾 (選廠壓衊醖構淵膚範餘, 壓餘獵淵壓夢範蓋簾願 ~ 獵憲衊網構壓膚鑰鏇遞) 更多