更新于：2024-11-01

STMN1

更新于：2024-11-01

基本信息

别名

C1orf215、chromosome 1 open reading frame 215、FLJ32206

+ [18]

简介

Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules. Prevents assembly and promotes disassembly of microtubules. Phosphorylation at Ser-16 may be required for axon formation during neurogenesis. Involved in the control of the learned and innate fear (By similarity).

关联

项与 STMN1 相关的药物

pbi-shRNA STMN1 Lipoplex

靶点

STMN1

作用机制

Stathmin蛋白抑制剂 [+1]

在研机构

Gradalis, Inc.

原研机构

Gradalis, Inc.

在研适应症

实体瘤

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

Anti-stathmin gene therapy(Gradalis, Inc.)

靶点

STMN1

作用机制

Stathmin蛋白抑制剂

在研机构-

原研机构

Gradalis, Inc.

在研适应症-

非在研适应症

实体瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 STMN1 相关的临床试验

NCT01505153 / Completed临床1期

Phase I Trial of Intratumoral Bi-functional shRNA Stathmin 1-knockdown Lipoplex in Patients With Advanced and/or Metastatic Cancer

This is a Phase I safety trial of bifunctional shRNA-STMN1 (pbi-shRNA™STMN1) BIV (bilamellar invaginated vesicle) lipoplex (LP), pbi-shRNA™ STMN1 LP administered by a single intratumoral (IT) injection. Patients with superficially accessible advanced cancer following prior therapies will be entered into the study following a modified dose escalation design based on the demonstrated safety of our previous clinical experience (BB-IND 13744) with the same liposome and vector DNA backbone expressing a different transgene (of which doses up to 7 mg DNA IV/single dose have been administered). Patients will accrue in 4-patient escalation cohorts using a modified Fibronacci escalation schema (100%-50%-33%-33%) at a starting intratumoral dose of 0.010 mg/kg of DNA through a dose of 0.053 mg/kg DNA intratumoral / single dose. Should a single, but not more than two (2), ≥ Grade 3 Dose Limiting Toxicity (DLT) occur in any cohort, following mandated review (see below) an additional two (2) patients will be accrued at that dose (total of six). If more than one ≥ Grade 3 toxicity occurs in any cohort, the preceding dose cohort will be expanded to six (from four) and if < 2/6 patients experience ≥ Grade 3 toxicity, that dose will be the Phase II recommended dose. Should no ≥ Grade 3 toxicity occur in any cohort (other than Grade 3 local injection site reaction), an additional two (2) patients will be treated at 0.053 mg/kg DNA intratumoral / single dose.

开始日期2012-02-01

申办/合作机构

Gradalis, Inc.

100 项与 STMN1 相关的临床结果

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100 项与 STMN1 相关的转化医学

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0 项与 STMN1 相关的专利（医药）

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1,484

项与 STMN1 相关的文献（医药）

2024-12-31·Annals of Medicine

Comprehensive scRNA-seq analysis to identify new markers of M2 macrophages for predicting the prognosis of prostate cancer

Article

作者: Liu, Mingming ; Jiang, Haiyang ; Ye, Chunwei ; Xia, Chengxing ; Zhu, Yong ; Ou, Yitian ; Yang, Delin

BACKGROUNDProstate cancer (PCa) has become the highest incidence of malignant tumor among men in the world. Tumor microenvironment (TME) is necessary for tumor growth. M2 macrophages play an important role in many solid tumors. This research aimed at the role of M2 macrophages' prognosis value in PCa.METHODSSingle-cell RNA-seq (scRNA-seq) data and mRNA expression data were obtained from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA). Quality control, normalization, reduction, clustering, and cell annotation of scRNA-seq data were preformed using the Seruat package. The sub-populations of the tumor-associated macrophages (TAMs) were analysis and the marker genes of M2 macrophage were selected. Differentially expressed genes (DEGs) in PCa were identified using limma and the immune infiltration was detected using CIBERSORTx. Then, a weighted correlation network analysis (WGCNA) was constructed to identify the M2 macrophage-related modules and genes. Integration of the marker genes of M2 macrophage from scRNA-seq data analysis and hub genes from WGCNA to select the prognostic gene signature based on Univariate and LASSO regression analysis. The risk score was calculated, and the DEGs, biological function, immune characteristics related to risk score were explored. And a predictive nomogram was constructed. CCK8, Transwell, and wound healing were used to verify cell phenotype changes after co-cultured.RESULTSA total of 2431 marker genes of M2 macrophage and 650 hub M2 macrophage-related genes were selected based on scRNA-seq data and WGCNA. Then, 113 M2 macrophage-related genes were obtained by overlapping the scRNA-seq data and WGCNA results. Nine M2 macrophage-related genes (SMOC2, PLPP1, HES1, STMN1, GPR160, ABCG1, MAZ, MYC, and EPCAM) were screened as prognostic gene signatures. M2 risk score was calculated, the DEGs, Immune score, stromal score, ESTIMATE score, tumor purity, and immune cell infiltration, immune checkpoint expression, and responses of immunotherapy and chemotherapy were identified. And a predictive nomogram was constructed. CCK8, Transwell invasion, and wound healing further verified that M2 macrophages promoted the proliferation, invasion, and migration of PCa (p < 0.05).CONCLUSIONSWe uncovered that M2 macrophages and relevant genes played key roles in promoting the occurrence, development, and metastases of PCa and played as convincing predictors in PCa.

2024-11-01·Gene

Integrated analysis of ferroptosis and stemness based on single-cell and bulk RNA-sequencing data provide insights into the prognosis and treatment of esophageal carcinoma

Article

作者: Li, Jing ; Wang, Wenjia ; Qin, Yanru ; Zhang, Daidi ; Jia, Yongxu ; Sui, Xin ; Xu, Jiayao

BACKGROUNDCancer stem cells (CSCs) play a significant role in the recurrence and drug resistance of esophageal carcinoma (ESCA). Ferroptosis is a promising anticancer therapeutic strategy that effectively targets CSCs exhibiting high tumorigenicity and treatment resistance. However, there is a lack of research on the combined role of ferroptosis-related genes (FRGs) and stemness signature in the prognosis of ESCA.METHODSThe cellular compositions were characterized using single-cell RNA sequencing (scRNA-seq) data from 18 untreated ESCA samples. 50 ferroptosis-related stemness genes (FRSGs) were identified by integrating FRGs with stemness-related genes (SRGs), and then the cells were grouped by AUCell analysis. Next, functional enrichment, intercellular communication, and trajectory analyses were performed to characterize the different groups of cells. Subsequently, the stem-ferr-index was calculated using machine learning algorithms based on the expression profiles of the identified risk genes. Additionally, therapeutic drugs were predicted by analyzing the GDSC2 database. Finally, the expression and functional roles of the identified marker genes were validated through in vitro experiments.RESULTSThe analysis of scRNA-seq data demonstrates the diversity and cellular heterogeneity of ESCA. Then, we identified 50 FRSGs and classified cells into high or low ferroptosis score stemness cells accordingly. Functional enrichment analysis conducted on the differentially up-regulated genes between these groups revealed predominant enrichment in pathways associated with intercellular communication and cell differentiation. Subsequently, we identified 9 risk genes and developed a prognostic signature, termed stem_ferr_index, based on these identified risk genes. We found that the stem-ferr-index was correlated with the clinical characteristics of patients, and patients with high stem-ferr-index had poor prognosis. Furthermore, we identified four drugs (Navitoclax, Foretinib, Axitinib, and Talazoparib) with potential efficacy targeting patients with a high stem_ferr_index. Additionally, we delineated two marker genes (STMN1 and SLC2A1). Particularly noteworthy, SLC2A1 exhibited elevated expression levels in ESCA tissues and cells. We provided evidence suggesting that SLC2A1 could influence the migration, invasion, and stemness of ESCA cells, and it was associated with sensitivity to Foretinib.CONCLUSIONThis study constructed a novel ferroptosis-related stemness signature, identified two marker genes for ESCA, and provided valuable insights for developing more effective therapeutic targets targeting ESCA CSCs in the future.

2024-11-01·International Immunopharmacology

Comprehensive genomic and spatial immune infiltration analysis of survival outliers in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy

Article

作者: Cai, Zijing ; Xie, Jingyuan ; Xu, Ke ; Wu, Xiaoying ; Wang, Fufeng ; Lv, Tangfeng ; Cheng, Qinpei ; Song, Yong ; Lu, Wanjun ; Zhan, Ping ; Jiang, Yuxin

BACKGROUNDA minority of patients with extensive-stage small cell lung cancer (ES-SCLC) exhibit prolonged survival following first-line chemoimmunotherapy, which warrants the use of reliable biomarkers. Here, we investigated the disparities in genomics and immune cell spatial distribution between long- and short-term survival of patients with ES-SCLC.METHODSWe retrospectively recruited 11 long-term (>2 years) and 13 short-term (<9 months) ES-SCLC survivors receiving first-line chemoimmunotherapy. The samples were processed using targeted next-generation sequencing (tNGS), programmed death ligand-1 staining, multiplex immunohistochemical staining for immune cells (mIHC), tumor mutation burden (TMB), and chromosomal instability score measurements. The expression of putative genes in SCLC at the bulk and single-cell RNA-sequencing levels, as well as the role of putative genes in pan-cancer immunotherapy cohorts, were analyzed.RESULTSAt the genomic level, a greater proportion of the smoking signature and higher TMB (>3.1) were associated with favorable survival. At the single-gene and pathway levels, tNGS revealed that MCL1 and STMN1 amplification and alterations in the apoptosis pathway were more common in short-term survivors, whereas alterations in the DLL3, KMT2B, HGF, EPHA3, ADGRB3, lysine deprivation, and HGF-cMET pathways were observed more frequently in long-term survivors. mIHC analysis of immune cells with different spatial distributions revealed that long-term survivors presented increased numbers of M1-like macrophages in all locations and decreased numbers of CD8⁺ T cells in the tumor stroma. Bulk transcriptomic analysis demonstrated that high levels of STMN1 and DLL3 represented an immune-suppressive tumor immune microenvironment (TIME), whereas HGF indicated an immune-responsive TIME. The expression levels of our putative genes were comparative in both TP53/RB1 mutant-type and TP53/RB1 wild-type. At the single-cell level, STMN1, MCL1, and DLL3 were highly expressed among all molecular subtypes (SCLC-A, SCLC-N, and SCLC-P), with STMN1 being enriched in cell division and G2M checkpoint pathways.CONCLUSIONSFor ES-SCLC patients receiving first-line chemoimmunotherapy, alterations in DLL3, KMT2B, HGF, EPHA3, and ADGRB3 and a greater proportion of M1-like macrophages infiltration in all locations were predictors of favorable survival, while MCL1 and STMN1 amplification, as well as a greater proportion of CD8⁺ T cells infiltrating the tumor stroma, predicted worse survival.

项与 STMN1 相关的新闻（医药）

2024-10-24

·今日头条

【Nature子刊】食管癌治疗新突破：高树庚团队单细胞测序揭示免疫治疗反应关键特征

【导读】新辅助免疫化疗（nICT）极大地改变了可手术食管鳞状细胞癌（ESCC）的治疗格局，但影响肿瘤对nICT反应的因素尚不清楚。在这项研究中，使用单细胞RNA测序与T细胞受体测序配对，团队分析了接受nICT治疗的ESCC患者的组织，并表征了肿瘤微环境的背景。 2024年10月22日，中国医学科学院肿瘤医院高树庚团队在期刊《Nature Communications》上发表了题为“Single-cell sequencing reveals immune features of treatment response to neoadjuvant immunochemotherapy in esophageal squamous cell carcinoma”的研究论文。研究结果强调了CXCL13作为辅助治疗提高免疫治疗疗效的潜力，确定了LRRC15 CAFs和SPP1巨噬细胞的富集是免疫治疗耐药的关键标志物。这些发现为未来研究改善ESCC免疫治疗反应的最佳策略，提供了理论依据。 https://www.nature.com/articles/s41467-024-52977-0 关于食管癌 01 食管癌（EC）是全球第七大最常见的恶性肿瘤，也是癌症死亡的第六大原因。食管鳞状细胞癌（ESCC）几乎占EC病例的90%，本质上是高度恶性的，在东亚尤其普遍。由于其症状不明显，大多数ESCC患者在晚期被诊断出来，导致5年总生存率低于20%。对于可切除的局部晚期ESCC患者，新辅助放化疗（nCRT）后进行食管切除术是目前的标准护理治疗，与单独手术相比，生存率更高。新辅助免疫治疗，尤其是免疫检查点阻断（ICB），显示出卓越的临床益处，并改变了各种实体瘤的治疗模式。对于晚期转移性ESCC，免疫化疗已被美国食品和药品监督管理局批准为一线治疗。新辅助免疫化疗（nICT）已显示出对可手术的局部晚期ESCC的有希望的益处，在不增加手术并发症发生率的情况下，实现高达50%的pCR率。这项研究将scRNA-seq与scTCR-seq配对，以研究18名接受nICT治疗的ESCC患者的细胞生物学和动力学。研究结果表明，CD8 Tex-CXCL13在应答者的治疗前肿瘤中显著富集，并且在相应的治疗后样本中，显示出更明显的祖细胞耗竭表型。这项研究阐明了对nICT治疗的不同反应的免疫特征，这对增强ESCC中的抗PD-1疗效具有潜在意义。 SPP1巨噬细胞和高表达SPP1的肿瘤细胞，是治疗后ESCC免疫治疗耐药的标志物 02 与接受nICT治疗的ESCC反应者相比，团队观察到Macro-SPP1、Macro-EREG和Macro-STMN1在治疗后无反应者中显著富集。scCODA分析还显示，Macro-SPP1、Macro-EREG和Macro-STMN1的浸润水平相对较高。而亚群Macro-SLC40A1则显示出相反的分布。这些证据证明，SPP1巨噬细胞可以促进肿瘤进展，介导TME重塑并限制对PD-L1阻断的反应。一致地，Macro-SPP1上调的DEGs显示与TME重塑相关的信号通路显著富集，包括细胞因子/趋化因子介导的信号通路和白细胞迁移。细胞间相互作用分析，揭示了Macro-SPP1与治疗后反应者和非反应者中的各种T细胞簇之间，存在不同的通信网。在nICT治疗期间，反应者中Macro-SPP1的浸润水平显著下降；而与治疗后无反应者相比，Macro-SPP1的浸润水平显著降低。在治疗后的ESCC中，发现Macro-SPP1和CD4 Treg-TNFRSF4之间存在显著的正相关，但在治疗前样本中则没有，这表明两个簇之间的相互作用，可能是由免疫化疗诱导的。这些发现揭示了Macro-SPP1是ESCC中免疫治疗耐药性的关键标志物，这可能通过细胞间相互作用激活Tregs并抑制CTL。凋亡信号通路的调节和对氧化/化学应激的反应显著富集，表明对细胞毒性T细胞和铂类化疗药物诱导的细胞凋亡耐药。与反应者相比，团队还发现SPP1在治疗后无反应者的残留肿瘤细胞中高表达。预计无反应者的残留ESCC肿瘤细胞，与CD8 Tn、CD8 Tex和CD8 Tem细胞的相互作用潜力增强。在TCGA-ESCA队列中，SPP1的高表达水平，成为重要的预后危险因素。在ESCC-nICT队列中，治疗后样本的SPP1表达，也是免疫化疗反应的重要预测因子。总之， SPP1巨噬细胞和高度表达SPP1的肿瘤细胞，是治疗后ESCC对免疫治疗耐药的标志物。 SPP1除了是免疫治疗反应的关键预测因子外，还与TME内的细胞毒性CD8 T细胞相互作用，最终限制抗肿瘤免疫。 SPP1作为免疫治疗耐药性的重要标志物。总结 03 主要发现： 1. CD8 T细胞（Tex）的终末耗竭和CD4调节性T细胞（Tregs）引起的高耐受性，是ESCC对免疫治疗耐药的主要因素； 2. 无反应者治疗后CD8 Tex-CXCL13浸润水平显著升高，且这些细胞对PD-1/PD-L1抑制剂的反应性有限； 3. 无反应者中CD4 Treg-TNFRSF4显著增加，与免疫抑制性特征相关，表明消除Treg障碍可能提高nICT疗效。 CXCL13的角色： 1. CD8 Tex-CXCL13在反应者中的预处理样本中深入渗透，可能作为nICT治疗效果的预测因子； 2. CXCL13的基线富集可能通过促进肿瘤相关三级淋巴结构（TLS）的形成和成熟，使肿瘤对免疫治疗敏感； 3. rmCXCL13能显著增强抗PD-1治疗在ESCC小鼠模型中的疗效。 CAFs和巨噬细胞的作用： 1. 治疗无反应者中升高的肿瘤相关成纤维细胞（tCAF-MMP11）与免疫治疗耐药性密切相关，并与CD4 Treg-TNFRSF4细胞比例正相关； 2. LRRC15 CAFs可能通过招募和激活免疫抑制性CD4 Tregs，来限制免疫治疗效果； 3. SPP1巨噬细胞和高度表达SPP1的肿瘤细胞是ESCC中免疫治疗耐药的关键标志物，可能通过靶向CD44抑制CD8 T细胞活化。参考资料： 1.Sung, H. et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J. Clin. 71, 209–249 (2021). 2.Chen, W. et al. Cancer statistics in China, 2015. CA A Cancer J. Clin. 66, 115–132 (2016). 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门推荐活动点击免费报名 🕓 上海｜11月15日-16日 ▶ 2024第一届中国类器官转化医学大会 🕓 上海｜11月21日-24日 ▶ 第七届上海国际肿瘤内科学论坛 🕓 全国｜2024年12月-2025年03月 ▶ 中国转化医学产业大会 🕓 上海｜2025年02月28日-03月01日 ▶ 第四届长三角单细胞组学技术应用论坛暨空间组学前沿论坛点击对应文字查看详情

免疫疗法临床研究

2024-09-26

·佰傲谷BioValley

LAG3抗体III期再败冷肿瘤

默沙东没能用LAG3抗体打开一门大癌种的市场。昨日，默沙东提供了该公司LAG3抗体favezelimab相关3期KEYFORM-007试验的最新情况。 KEYFORM-007试验是采用LAG3+PD-1抗体的组合来治疗PD-L1阳性，接受过标准治疗后微卫星稳定(MSS)转移性结直肠癌(mCRC)患者，选择的对照组是采用拜耳的瑞戈非尼或大鹏制药的TAS-102。然而，相比于对照组，favezelimab+K药的联合疗法并没有达到总生存期(OS)的主要终点。默沙东关于微卫星稳定（MSS）转移性结直肠癌这一直肠癌中占比高达90%的大癌种尝试可能就此宣告失败。冷肿瘤免疫疗法难治 MSS转移性结直肠癌是典型的冷肿瘤，对免疫疗法的应答率普遍很低，业内公认大多数MSS转移性结直肠癌几乎不可能从如PD-1抗体等免疫疗法中获益，所以一般标准治疗方法一般是靶向药和放化疗。 PD-1+LAG3的组合得到BMS和默沙东的应用主要还是因为之前的研究探索下发现的：结直肠癌患者中确实有LAG3表达上调，辅助放疗后，患者也会出现PD-1和LAG3表达增加，体外临床也表明使用LAG3抗体能够恢复肿瘤浸润T细胞的反应效果，再加上LAG3+PD-1的组合此前也被证明有协同机制。因此BMS就率先开发了LAG3人源抗体Relatlimab。 Relatlimab+O药的组合也被应用到了MSS转移性结直肠癌。默沙东也紧随其后，一同在这大癌种的市场中争锋相对。而这一大癌种适应症市场的另外一位参与者是Agenus，不过Agenus采用的组合是PD-1+CTLA4的经典组合。Agenus的I/II期数据相当不错，反应率约在20%，中位OS为21.2个月。问题是Agenus公司本身财务出现了状况，裁员不止，因此就想要寻求联合临床的迅速上市挽回公司颓势。但是FDA的态度很明确，ORR上的优势并不一定能够转化为OS的优势，因此要求这家公司做III期临床证明效果。从适应症开发来看，同一适应症的竞争对手BMS和默沙东都开启了III期临床，如果就这样让Agenus的加速批准上市可能有失公正。从疗效转化来看，FDA认为ORR优势无法转化为OS优势的观点很可能是对的。去年12月BMS认为Relatlimab+O药的组合很大可能不会达到OS主要终点，因此放弃这一癌种。而如今默沙东同样败在了这一癌种下，可能预示着一部分免疫疗法确实很难在MSS转移性结直肠癌这一癌种中大展身手。相关综述性文献倒是认为，免疫疗法去联合抗VEGF TKI、其他免疫调节药物和BRAF抑制剂可能更为有效。 favezelimab还有其他上市机会当然此次失败更像是大市场下的试错，favezelimab还有其他上市机会。另外一个处于III期临床的是favezelimab相关临床是KEYFORM-008，这次适应症是复发或难治性经典霍奇金淋巴瘤患者中LAG+PD-1的组合。预计将于2027年完成临床。目前BMS的Relatlimab是已经凭借黑色素瘤的适应症上市了，Relatlimab+O药的组合Opdualag23年全年销售额达到了6.27亿美元，按照今年Q1和Q2的增长势头今年或许能达到10亿美元大关。参考来源： Guven DC, et al. The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review. Oncologist. 2024:oyae013. https://www.merck.com/news/merck-provides-update-on-phase-3-keyform-007-trial-evaluating-investigational-fixed-dose-combination-of-favezelimab-and-pembrolizumab-for-patients-with-previously-treated-pd-l1-positive-microsatellite/ 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

免疫疗法临床3期临床2期加速审批临床失败

2024-09-19

·生物制药小编

LAG-3闯入非小细胞肺癌

作为同一批被寄予厚望的下一免疫检查点，相比一直让人提心吊胆、大起大落的TIGIT，LAG3给人的确定性强了不少。虽然LAG3的疗效（主要是联合疗法）没达到惊艳的程度，但是胜在稳妥，毒性较低。 2022年3月，首个LAG-3靶向药Opdualag获得FDA批准上市，与PD-1抗体Opdivo联合用于12岁及以上患者不可切除或转移性黑色素瘤。百时美施贵宝也加入了非小细胞肺癌中这个竞争火热的战局。近日，在欧洲肿瘤内科学会（ESMO）大会中，BMS报告了Opdualag的Ⅱ期临床试验RELATIVITY-104试验数据。这是首个评估含有LAG-3阻断抗体作为转移性非小细胞肺癌（NSCLC）患者一线治疗方案的随机II期临床试验。 RELATIVITY-104主要评估了与“Opdivo+化疗”相比，“Opdualag+化疗”作为IV期或复发性NSCLC患者一线疗法的有效性与安全性，主要终点是盲态独立中心评估的总缓解率（ORR），次要终点包括无进展生存期（PFS）、以及按生物标志物亚组划分的ORR/PFS。就目前公布的数据看来，在全部人群中，“Opdualag+化疗组”相比“Opdivo+化疗组”在ORR和PFS上所取得的优势都比较微弱，ORR分别为51.3% 和43.7%，PFS分别为6.7个月和6.0个月，中位缓解持续时间（mDOR）分别为10.1个月（7.4–未达到）和9.1个月。不过在预先指定的亚组中，相比“Opdivo+化疗组”，“Opdualag+化疗组”中所呈现的ORR和PFS获益趋势就凸显出来了。在PD-L1≥1%表达亚组中，“Opdualag+化疗组”显示出53.2%的ORR和9.8个月的PFS，而“Opdivo+化疗组”ORR为40.8%，PFS为6.1个月。这种获益在非鳞状NSCLC亚组中进一步加强，“Opdualag+化疗组”的46.7%的ORR和8.3个月的PFS，而“Opdivo+化疗组”ORR为38.5%，PFS为6.0个月。在PD-L1表达≥1%且非鳞状亚组中，“Opdualag+化疗组”实现了58%的ORR，对照组中仅为39.6%。“Opdualag+化疗组”还显著延长了PFS，达到11.6个月，而对照组为6.9个月。截至数据统计截止时，总体生存期数据仍不成熟。基于这次得到的数据，BMS将启动一项与“Keytruda+化疗”比较的Ⅲ期临床试验RELATIVITY-1093（作为一线疗法），招募的目标患者为PD-L1表达率在1%至49%之间的非鳞状NSCLC患者。另外，BMS还计划明年启动另一项针对PD-L1表达≥50%非鳞状NSCLC患者的Ⅲ期临床试验。除了Opdualag之外，Immutep公司的LAG-3融合蛋白Eftilagimod也在探索在NSCLC中治疗潜力，Eftilagimod与Keytruda联用的治疗方案已经进入了Ⅲ期阶段。在去年的ESMO上，Immutep披露了Eftilagimod联合K药作为NSCLC一线治疗的Ⅱ期临床TACTI-002数据，结果显示，Eftilagimod+Keytruda显示了40.4%的ORR和21.6个月的mDOR。总结 BMS对Opdualag的临床开发策略是相对谨慎的，在黑色素瘤中的成功并没有让BMS立即跳进肺癌这个失败率仍然很高的领域。BMS的首席医学官Samit Hirawat博士也将Opdualag的开发描述为“一场缓慢的行军”。不过，LAG靶向疗法想要提升在肿瘤免疫疗法领域的地位，需要在黑色素瘤之外的其他实体瘤瘤种中取得III期阳性结果，进一步验证其作为PD-1强搭档的临床价值。参考出处： https://www.fiercepharma.com/pharma/bristol-myers-moves-opdualag-phase-3-trials-competitive-first-line-lung-cancer-field?itm_source=parsely-api https://oncologypro.esmo.org/meeting-resources/esmo-congress-2024/nivolumab-nivo-plus-relatlimab-with-platinum-doublet-chemotherapy-pdct-vs-nivo-pdct-as-first-line-1l-treatment-tx-for-stage-iv-or-recurre

临床3期临床结果上市批准临床2期免疫疗法