CDKN2A

尿路上皮癌（UC）是一种常见且致命的癌症，具有显著的遗传异质性【1】。在癌症发展过程中，突变过程和DNA修复之间不断相互作用，导致产生独特的突变特征和广泛的基因组结构变化。APOBEC3家族的胞嘧啶脱氨酶可在多种人类癌症的基因组中引起胞嘧啶向胸腺嘧啶或鸟嘌呤的替换，形成体细胞突变特征，尤其是在UC中。研究发现，APOBEC3酶家族在多种癌症中引起的突变模式与癌症的进展和耐药性密切相关【2】。尽管已有研究探讨了化疗对癌症突变的影响，初步探索了化疗耐药性晚期UC的进化动态【1】，但关于内源性突变压力（如APOBEC3）和外源性突变过程（如化疗）的相对时序、克隆性及其对UC进化的影响仍存在许多未解之谜；复杂结构变异（SV），包括染色体外DNA（ecDNA），如何影响UC的进化和药物抗性也尚未可知。毫无疑问，这些基本问题的回答将有助于对晚期癌症患者的临床发展的预测并预防化疗耐药。 为了解决这些问题，近日，来自美国威尔康奈尔医学院的Bishoy M. Faltas团队在Nature上在线发表题为The interplay of mutagenesis and ecDNA shapes urothelial cancer evolution的文章，通过全基因组测序（WGS）分析了尿路上皮癌的原发性和转移性肿瘤样本，探讨了APOBEC3和化疗引起的突变特征及其在肿瘤进化中的作用，使用连接平衡分析（JaBbA）工具分析了复杂结构变异，特别是ecDNA的形成，并研究了这些变异如何影响肿瘤对治疗的抗性。此外，研究人员还利用长读长测序技术详细绘制了ecDNA的环形结构，并在实验模型中证实了CCND1 ecDNA在促进治疗抗性中的优势。这些发现揭示了驱动尿路上皮癌进化的新机制，为开发新疗法提供了潜在靶点，具有重要的治疗意义。 本文研究人员首先通过WGS分析了77个UC肿瘤样本，包括28个铂类化疗前和49个化疗后的样本，发现APOBEC3胞苷脱氨酶是UC中主要的突变酶，其引起的单碱基替换（SBS2和SBS13）以及双碱基替换（DBS11）在所有突变中占有显著比例。此外，与铂类化疗相关的SBS31、SBS35和DBS5突变特征在化疗后的肿瘤样本中也有贡献。通过构建系统发育树，研究人员确定了APOBEC3引起的突变主要发生在肿瘤早期，并且具有克隆性，而化疗引起的突变则更多出现在晚期，且为亚克隆性。APOBEC3引起的突变与化疗引起的突变在时间上有明显的先后顺序，APOBEC3突变较早，化疗突变较晚（图1）。此外，化疗引起的突变速率高于APOBEC3，这表明化疗不仅是治疗手段，也是癌症进化的驱动力。研究还发现，APOBEC3引起的突变在正常尿路上皮和肿瘤之间共享，这强调了APOBEC3在UC早期发生和发展中的作用。这些结果表明早期由APOBEC3酶引起的突变推动了UC的发生，同时显示了早期克隆性的APOBEC3引起的突变与晚期亚克隆性的化疗引起的突变之间的相互作用，这两种突变共同塑造了癌症的转移性和治疗抗性表型，提示APOBEC3和化疗引起的突变在UC的发展和对治疗的抵抗性中扮演了关键角色。 基因组不稳定性来自突变和复杂的大规模染色体变异之间的相互作用，为了研究这些过程，研究人员使用连接平衡分析（JaBbA）工具对威尔康奈尔医学院(WCM)-UC队列中的高阶SV进行了全面分析。研究结果发现大多数样本中存在多个复杂SV，其中模板插入链（TIC）、染色体碎裂（chromoplexy）和断裂-融合-桥接（BFB）事件最为常见。此外，研究还观察到与TP53基因突变相关的样本在基因组改变、总连接点数量和特定SV类别方面有显著增加，暗示了基因组稳定性基因突变在复杂SV形成中的重要性。癌细胞ecDNA是扩增癌基因的兆碱基规模的环状DNA亚类，研究人员进一步专注于检测形成ecDNA的SV的两个定义特征：高拷贝数的扩增子和环状结构。结果发现约35%的样本中含有可能生成ecDNA的SV事件，这突出了它们在UC中的高发病率，提示这些ecDNA形成事件可能在癌症的进化和治疗抗性中起着关键作用。与此同时，研究人员发现APOBEC3酶和化疗都能在UC中的ecDNA上引起突变。APOBEC3诱导的聚集突变（kyklonas）多发生在ecDNA形成早期，且靠近结构变异的断点，暗示其在ecDNA形成中扮演关键角色，APOBEC3诱导的突变和ecDNA的生物发生在空间和时间上是重叠的。相比之下，化疗诱导的突变主要出现在晚期，且变异等位基因频率（VAF）较低，表明它们在肿瘤发展中出现较晚。 随后，研究人员探讨了UC中由ecDNA驱动的癌基因扩增现象。利用FishHook工具分析复发性结构变异，研究人员发现其中55%的变异发生在与癌症相关的基因附近，特别是CCND1基因，它在大多数样本中通过ecDNA形成结构变异而扩增。此外，研究人员还观察到，与CCND1扩增相关的肿瘤样本中，CDKN2A基因（编码抑制CDK4/6的肿瘤抑制因子p16）的纯合缺失更为常见，提示ecDNA介导的CCND1扩增的UC肿瘤激活了p16–cyclin D1–CDK4/6–RB1通路，促进了细胞周期的进程。与此同时，研究人员分析了在系统治疗下CCND1 ecDNA形成SV的动态变化，结果发现在系统治疗后，UC中CCND1 ecDNA形成的结构变异事件变得更加复杂，拷贝数增加，提示ecDNA在选择性治疗压力下可能作为适应性储备，促进了耐药性的产生。进一步地，通过高级的ONT（Oxford Nanopore Technologies）长读长全基因组测序技术，研究人员详细描绘了UC中CCND1基因所在的ecDNA形成结构变异的环形结构，发现每个ecDNA扩增子在结构上都是独特的，并且会获取不同癌基因的启动子、增强子和超级增强子。这些ecDNA扩增子通常包含癌基因FGF3、FGF4和FGF19的扩增，并保留了CCND1局部启动子和调控元件。 最后，研究人员通过实验模型，利用非整合性慢病毒载体在膀胱癌细胞中模拟了CCND1 ecDNA，并在顺铂化疗下进行了竞争实验，发现携带CCND1 ecDNA的细胞显示出更高的适应性。单细胞RNA测序分析揭示了这些细胞中E2F信号通路和其他与化疗抗性相关的通路的激活。此外，通过敲低依赖CCND1 ecDNA的癌细胞中的CCND1，研究人员观察到细胞适应性的降低。这些结果表明CCND1 ecDNA的获得显著增强了肿瘤细胞对化疗的适应性。 综上所述，本研究对晚期UC患者的不同解剖区域和连续时间点收集的配对样本进行了WGS，分析揭示了两种关键致突变因素——APOBEC3胞嘧啶脱氨酶和基于铂的化疗——在UC进展中的活动时间线，全面绘制了晚期UC中的复杂SV，阐明了驱动UC进化的基本机制，为未来的研究以及开发旨在阻断尿路上皮癌变和治疗抗性的创新治疗策略带来了希望。 参考文献 1. Faltas, B. M. et al. Clonal evolution of chemotherapy-resistant urothelial carcinoma. Nat. Genet. 48, 1490–1499 (2016). 2. Swanton, C., McGranahan, N., Starrett, G. J. & Harris, R. S. APOBEC enzymes: mutagenic fuel for cancer evolution and heterogeneity. Cancer Discov. 5, 704–712 (2015). https://doi-org.libproxy1.nus.edu.sg/10.1038/s41586-024-07955-3 内容来源于网络，如有侵权，请联系删除。

- Interim data for fadraciclib monotherapy in patients with advanced solid tumors preselected for CDKN2A and/or CDKN2B abnormalities -BERKELEY HEIGHTS, N.J., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Cyclacel Pharmaceuticals, Inc. (NASDAQ: CYCC, NASDAQ: CYCCP; "Cyclacel" or the "Company"), a biopharmaceutical company developing innovative cancer medicines, today announced that initial safety and efficacy data from twelve patients with advanced solid tumors enrolled in the Phase 2 part of the 065-101 clinical study of fadraciclib, or “fadra”, as a single agent was presented as a poster at the 2024 EORTC-NCI-AACR 36th Symposium on Molecular Targets and Cancer Therapeutics (“Triple Meeting”), in Barcelona, Spain (October 23-25, 2024). The patients were enrolled in the biomarker-enriched, Cohort 8 of the proof of concept study and were preselected for CDKN2A and/or CDKN2B abnormalities. “We are encouraged by the interim data of cohorts 6 and 8 in our Phase 2 study of fadra,” said Spiro Rombotis, President and Chief Executive Officer. “Although the data in Cohort 8 is immature with ongoing patients still to have a first scan and being followed up, we continue to see good tolerability and signals of efficacy in patients with CDKN2A/B abnormalities that have had their first scan and follow-up evaluation. We are grateful to our investigators, the patients and their families for their support of this important study.” Interim Phase 2 Data Fadraciclib was well tolerated in Cohort 8. Most common drug-related adverse events included diarrhea, nausea, vomiting and were similar to those seen at this dose in Phase 1. There were no Grade 3 or higher treatment-emergent adverse events in the Phase 2 study this far, consistent with the Phase 1 data. The majority of patients (12/14) had ECOG performance status of 1 and median number of prior therapies was 3. In Cohort 8, four patients had pancreatic cancer, and one each cholangiocarcinoma, duodenal, melanoma, cervical, laryngeal, ovarian, squamous cell cancer with unknown primary (CUP) and thymus cancer. Out of six patients evaluable for efficacy, two achieved stable disease: a melanoma patient whose treatment duration was 125 days and a squamous cell CUP patient who achieved 11% tumor shrinkage in the sum of all lesions on first scan with treatment duration of over 85 days (ongoing). Two additional patients with ovarian and laryngeal cancer are ongoing but have not had their first scan yet. The most common molecular characteristics of Cohort 8 patients were loss of function or deletion of CDKN2A and/or CDKN2B tumor suppressor genes. Other pharmacogenomic observations included CDKN2A/B, KRAS and/or TP53 mutations. Study Design Two Phase 2 dose expansion cohorts in the 065-101 study were initiated. Cohort 8 prospectively enrolled 12 patients with known CDKNA/B genetic alterations between April and September 2024. The rationale was to further evaluate observations of clinical activity in Phase 1 patients with known CDNK2A or CDKN2B genetic alterations. Cohort 6 is enrolling patients with T-cell Lymphoma with two patients treated so far. The rationale was to further evaluate observations of partial response (PR) in 2/3 Phase 1 patients with T-cell lymphoma. Certain T-Cell lymphomas are known to harbor CDNK2A genetic alterations. All patients were treated with oral fadraciclib 100mg BID, M-F, week 1-4 in 28-day cycles which was the Recommended Phase 2 dose (RP2D). The primary objectives of the 065-101 study in the Dose Escalation stage are to determine maximum tolerated dose (MTD) and/or RP2D and in the Phase 2, Proof of Concept stage to evaluate preliminary efficacy of fadraciclib as measured by overall response rate (ORR). The secondary objectives in Dose Escalation are to assess safety and tolerability, pharmacokinetics, and ORR, while in Phase 2, Proof of Concept, to assess safety and tolerability, evaluate disease control rate (DCR), duration of response (DOR), progression free survival (PFS), and overall survival (OS). The study is utilizing a Simon two-stage optimal design to evaluate clinical activity. Exploratory objectives include investigation of clinical pharmacodynamics (PD) and pharmacogenomics (PGx). Further information from the poster is available at: Link to poster About Fadraciclib Fadraciclib is a highly selective CDK2 (IC50=5 nM) and CDK9 (IC50=26 nM) inhibitor causing anaphase mitotic catastrophe and apoptotic death of cancer cells at sub-micromolar concentrations. Retrospective review of the dose escalation portion of Phase 1 studies suggested clinical activity in patients with known CDNK2A or CDKN2B genetic alterations. In a Phase 1 study of intravenous fadraciclib monotherapy (065-01) a heavily pretreated endometrial cancer patient with CDNK2A, CDKN2B and PRMT5 loss achieved confirmed complete response (CR). In the Phase 1 oral fadraciclib monotherapy study (065-101), 7/38 treated patients were found to have known CDKN2A/B genetic alterations, of which 6 were evaluable for efficacy. A PTCL patient with CDKN2A P114L mutation reported a partial response (PR). A squamous cell NSCLC patient with CDKN2B loss reported stable disease (SD) and 22% reduction in tumor volume in the sum of all target lesions. A metastatic, testicular Leydig germ cell cancer patient with CDKN2A, CDKN2B and MTAP loss reported 12% reduction in tumor volume in the sum of all target lesions. The overall response rate (ORR) was 17% (1/6) and the disease control rate (DCR) was 100% (6/6). About Cyclacel Pharmaceuticals, Inc. Cyclacel is a clinical-stage, biopharmaceutical company developing innovative cancer medicines based on cell cycle, transcriptional regulation and mitosis biology. The transcriptional regulation program is evaluating fadraciclib, a CDK2/9 inhibitor, and the anti-mitotic program plogosertib, a PLK1 inhibitor, in patients with both solid tumors and hematological malignancies. Cyclacel's strategy is to build a diversified biopharmaceutical business based on a pipeline of novel drug candidates addressing oncology and hematology indications. For additional information, please visit www.cyclacel.com. Forward-looking Statements This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include, among other things, statements related to the efficacy and safety profile of fadraciclib in an incomplete clinical trial, Cyclacel’s future plans and prospects, Cyclacel’s anticipated cash runway and the planned timing of data results and continued development of fadraciclib. Factors that may cause actual results to differ materially include market and other conditions, the risk that product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later clinical trials, trials may have difficulty enrolling, Cyclacel may not obtain approval to market its product candidates, the risks associated with reliance on outside financing to meet capital requirements, the risks associated with reliance on collaborative partners for further clinical trials, development and commercialization of product candidates and Cyclacel’s ability to regain and maintain compliance with Nasdaq’s continued listing requirements, although no assurance to that effect can be given. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "potential," "expects," "plans," "anticipates," "intends," "continues," "forecast," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to our most recent Annual Report on Form 10-K and other periodic and other filings we file with the Securities and Exchange Commission and are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and we assume no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Contact Company: Paul McBarron, (908) 517-7330, IR@cyclacel.com © Copyright 2024 Cyclacel Pharmaceuticals, Inc. All Rights Reserved. The Cyclacel logo and Cyclacel® are trademarks of Cyclacel Pharmaceuticals, Inc.

01 行业新闻 丨国家卫健委印发《2024年版肥胖症诊疗指南》 10月17日，国家卫健委印发《2024年版肥胖症诊疗指南》，这是国内首部肥胖多学科诊疗的权威指南，对规范我国肥胖症临床诊疗，提高医疗机构肥胖症诊疗同质化水平具有重要意义。 指南对肥胖症进行了四类分级。长期以来，中国对于肥胖症的定义是：BMI达到24 kg/m²且低于28 kg/m²为超重，达到或超过28 kg/m²为肥胖。不过，这一划分方式已经不再适应当前的人群肥胖状况。因此，新的指南中将肥胖症继续细分为轻度、中度、重度、极重度四个等级，方便临床对症治疗。 新版指南加入了药物治疗部分：当超重且伴有至少一种体重相关合并症，如血糖、血脂、血压异常，非酒精性脂肪性肝病，阻塞性呼吸睡眠暂停综合征、肿瘤等多种疾病的时候，可在联合应用减重药物进行治疗。 指南共推荐5款肥胖治疗药物。除传统的奥利司他之外，利拉鲁肽、贝那鲁肽、司美格鲁肽、替尔泊肽4款产品均是GLP-1类药物。（健识局） 02 企业动态 丨迪哲医药肺癌新药舒沃替尼获第4项突破性疗法认定 10月13日，迪哲医药宣布，中国国家药品监督管理局药品审评中心（CDE）将其新型肺癌靶向药舒沃哲（通用名：舒沃替尼片）纳入突破性治疗品种，用于未接受过系统性治疗、携带表皮生长因子受体（EGFR）20号外显子插入突变（exon20ins）的局部进展或转移性非小细胞肺癌（NSCLC）。随着此次又一项突破性治疗品种的认定，该产品已获得4次突破性疗法认定。公开信息显示，早前，舒沃替尼片二线/后线治疗EGFR exon20ins NSCLC的适应症在中国被NMPA纳入突破性治疗品种以及在美国被FDA授予突破性疗法认定。（迪哲医药） 丨湃隆生物癌症新药获批临床 10月14日，湃隆生物宣布该公司研发的二代MTA协同PRMT5抑制剂GTA182的临床试验申请（IND）已经获得中国国家药品监督管理局批准，拟开发用于治疗MTAP缺失的实体瘤。蛋白精氨酸甲基转移酶5（PRMT5）抑制剂是一类新兴的抗肿瘤药物，也被认为是继PARP抑制剂之后下一波有希望的“合成致死”疗法之一，它可与MTAP基因突变构成“合成致死”搭档。MTAP（甲硫腺苷磷酸化酶）与抑癌基因CDKN2A在10%~15%的各类肿瘤患者中共同缺失。（湃隆生物） 丨荣昌生物ADC新药维迪西妥单抗乳腺癌适应症申报上市 10月15日，CDE官网最新公示，荣昌生物的靶向HER2的抗体偶联药物（ADC）注射用维迪西妥单抗新适应症上市申请获得受理。根据CDE官网，该上市申请已经于今年9月被纳入优先审评，适用于既往接受过曲妥珠单抗或其生物类似物和紫杉类药物治疗的HER2阳性（HER2免疫组织化学检查结果为3+或FISH+）存在肝转移的晚期乳腺癌患者。维迪西妥单抗（RC48）是荣昌生物研发的靶向HER2的ADC，目前已有胃癌、尿路上皮癌两大适应症在中国获批上市。（荣昌生物） 丨恒瑞PD-1再次申报在美上市 10月15日，恒瑞医药公告称，重新提交的卡瑞利珠单抗许可申请已获FDA受理，申报适应症为卡瑞利珠单抗联合阿帕替尼，用于不可切除或转移性肝癌的一线治疗。恒瑞在公告中披露，卡瑞利珠单抗联合阿帕替尼是晚期肝癌一线治疗最长OS获益组合。最新结果显示，该联用方案相比于标准治疗，中位总生存期显著延长，达到了23.8个月。此次申报是恒瑞“双艾”组合第二次冲击在美上市。今年5月，恒瑞医药公告：该PD-1联用方案上市申请遭到FDA拒绝，给出的原因是生产相关的问题。（恒瑞医药） 丨海创药业口服蛋白降解剂获批临床 10月15日，海创药业宣布其1类新药HP568片在中国获得临床试验默示许可，拟开展用于治疗雌激素受体（ER）阳性和人表皮生长因子受体2（HER2）阴性的晚期乳腺癌（ER+/HER2-晚期乳腺癌）的临床试验。HP568是海创药业自主研发的靶向降解ERα的口服蛋白降解靶向嵌合体（Proteolysis Targeting Chimera，PROTAC）药物，由靶蛋白配体、E3连接酶配体和两配体间的连接子3部分构成，拟用于治疗ER+/HER2-晚期乳腺癌。（海创药业） 丨金赛药业癌症1类新药在美国获批临床 10月15日，长春高新发布公告称，其子公司金赛药业GenSci122片项目获得美国FDA新药临床试验默示许可。GenSci122是由金赛药业自主研发的一种具有新型结构的小分子KIF18A抑制剂，也是一款基于“合成致死”机制的抗肿瘤新药。在中国，GenSci122以注册分类1类申报的临床研究申请已经于今年9月底获得CDE受理。KIF18A是一个“合成致死”靶点。KIF18A抑制剂与染色体不稳定（CIN）及全基因组加倍 （WGD）+构成合成致死。据长春高新公告介绍，GenSci122片是一种有效的选择性KIF18A抑制剂，具有显著区别于其他细胞周期和抗有丝分裂药物靶点的抗肿瘤特征。（金赛药业） 丨和其瑞医药皮下注射抗体1类新药拟纳入突破性治疗品种 10月15日，CDE官网最新公示，和其瑞医药申报的1类新药HMI-115拟纳入突破性治疗品种，适应症为治疗子宫内膜异位症相关的中重度疼痛。公开资料显示，HMI-115是一款靶向泌乳素受体（PRLR）的单抗新药，和其瑞医药拥有该产品的全球权益。HMI-115是一款靶向PRLR的单抗新药。研究表明，PRLR表达失调可能与子宫内膜异位症的发病机制有关，而靶向催乳素和催乳素受体的药物可能改善和控制该疾病相关的疼痛。2019年4月，和其瑞医药与拜耳公司（Bayer）就开发与产业化靶向PRLR的单克隆抗体HMI-115签署了一项全球独家许可协议，由和其瑞医药在全球开展该产品多个适应症的开发和产业化。（和其瑞医药） 丨华东医药合作开发ADC癌症新药在中国获批临床 10月16日，CDE官网最新公示，由Heidelberg Pharma申报的1类新药HDP-101获批临床，拟用于治疗B细胞成熟抗原（BCMA）阳性克隆性血液学疾病（如复发/难治性多发性骨髓瘤）。公开资料显示，这是一款靶向BCMA的抗体偶联药物（ADC），由华东医药合作开发。公开资料显示，HDM2007为一款靶向B细胞成熟抗原（BCMA）的ADC。该产品携带合成的蘑菇毒素α-鹅膏蕈碱肽衍生物amanitin作为有效载荷。Amanitin具有新的作用方式，可抑制RNA聚合酶II，有效阻止转录并诱导肿瘤细胞凋亡，无论其增殖状态如何。（华东医药） 丨微芯生物癌症1类新药申报临床 10月17日，微芯生物宣布其递交的用于治疗肿瘤的1类创新药CS231295片临床试验申请获CDE受理。根据新闻稿，CS231295是微芯生物自主研发的脑透过性小分子多靶点蛋白激酶抑制剂，对于携带特定抑癌基因缺陷的肿瘤，可产生合成致死效应。根据微芯生物新闻稿介绍，CS231295对于携带特定抑癌基因缺陷的肿瘤可产生合成致死效应，并带来针对性的药效，为这类肿瘤患者提供了新的治疗选择。同时，CS231295具有显著的抗肿瘤血管生成作用，能实现广谱的抗肿瘤活性。未来，无论是单药或与其他抗肿瘤药物联合使用，都有望为多种肿瘤提供差异化的创新治疗方案。（微芯生物） 丨原启生物双靶点CAR-T细胞疗法获批临床 10月17日，CDE官网最新公示，原启生物1类新药OriC613注射液获批临床，拟开发治疗晚期实体瘤。根据原启生物新闻稿介绍，这是其自主研发的双靶点Claudin 18.2/MSLN自体CAR-T细胞治疗药物。OriC613获批IND是原启生物在新药开发道路上的又一重要里程碑。为解决实体肿瘤On-Target/Off-Tumor毒性问题,OriC613采用了创新性的双受体逻辑门控设计策略，只有在同时识别两种特定肿瘤抗原时才能激活T细胞，并已经在临床前获得很好的数据验证。（原启生物） 丨默沙东肺动脉高压新药在中国申报上市 10月17日，CDE官网最新公示，默沙东申报的注射用sotatercept上市申请获得受理。公开资料显示，这是一款“first-in-class”新型激活素信号抑制剂类生物制剂，该产品已经于今年3月获得美国FDA批准上市，用于治疗肺动脉高压（PAH）。这款疗法此前被行业媒体Evaluate评为2024年潜在重磅的疗法之一。Sotatercept是一款IIA型激活素受体（ActRIIA）融合蛋白。在临床前研究中，它可以逆转肺动脉壁和右心室的重塑。该产品也是默沙东于2021年以约115亿美元收购Acceleron Pharma公司获得的关键疗法。此前，sotatercept已获得FDA授予的突破性疗法认定，用于治疗肺动脉高压。（默沙东） 丨阿斯利康癌症免疫联合疗法在中国申报上市 10月18日，CDE官网最新公示，阿斯利康两款新药的上市申请获得受理，具体适应症尚未披露。度伐利尤单抗（durvalumab）注射液为一款PD-L1抑制剂，tremelimumab为一款抗CTLA-4单抗。从受理号可以推测，本次申报上市的可能为二者组成的联合疗法，该联合疗法此前在全球范围内获监管机构批准用于治疗非小细胞肺癌一线治疗和肝细胞癌一线治疗。度伐利尤单抗是一种人源化的PD-L1单克隆抗体，能够阻断PD-L1与PD-1和CD80的结合，从而阻断肿瘤免疫逃逸策略并恢复被抑制的免疫反应。（阿斯利康） *声明：本文不构成任何投资建议，仅出于传递更多信息之目的。 ------------------------------ 「长按」二维码添加小达「进群」 与更多行业伙伴共探市场前沿资讯 艾美达医药咨询 艾美达（北京）医药信息咨询有限公司，成立于2014年4月，是一家专业的医药行业咨询服务提供商。公司致力于将产业政策研究与真实世界的数据挖掘深度结合，洞悉行业政策对市场的影响，通过专业的研究提供前瞻性的市场分析，为企业产品上市后的市场准入提供整体解决方案。