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免疫疗法以外的新型疗法.pdf

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1、Novel Therapies Outside Immunotherapy in RCCThai H.Ho,MD,PhDAssociate ProfessorBlatt-Ness Endowed Oncology ChairHollings Cancer Center Medical University of South CarolinaDisclosuresAdvisory board/consulting from Breakthrough Scientific,Cardinal Health,Exelixis,Ipsen,GlaxoSmithKline,Johnson and John

2、son,Merck,Neomorph,Novartis,Taiho Oncology.Royalties/patents from Champions Oncology,licensing of QSOX1 small molecule inhibitors,licensing of QSOX1 monoclonal antibodies,licensing of Galectin antibodies,licensing of Treg screening methods.EXCLUSION ZONE Doesnt respond to traditional cytotoxic chemo

3、therapy and has intra-tumoral heterogeneity Low incidence of traditional driver mutations(KRAS,TP53);high incidence of chromatin remodeling mutations which may facilitate metabolic reprogramming of the tumor and cross-talk with the microenvironment-mab(monoclonal antibodies)-tinib(tyrosine kinase in

4、hibitors)-tifan(HIF-2 inhibitors)-limus(mTOR inhibitors)Created in https:/BioR;US Adopted Names(USAN),WHO INNKidney cancer doesnt follow a traditional cancer playbookBelzutifan+Cabozantinib Combination in 1LLITESPARK-003 Cohort 1(IO nave)EXCLUSION ZONEORRPFSOSIpilimumab+nivolumab(P3-CM214)4012.452.7

5、Axitinib+pembrolizumab(P3-KN426)6115.747.2Cabozantinib+nivolumab(P3-CM9ER)5616.446.5Lenvatinib+pembrolizumab(P3-CLEAR)7123.953.7Belzutifan 120 mg+cabozantinib 60 mg(P2-Choueiri T Lancet Oncol.2025,N=50)7030.3NRChoueiri TK,Bauer RM et al.Lancet Oncol.Jan 2025.Zanzalintinib+Immunotherapy Combination i

6、n 1LSTELLAR-002EXCLUSION ZONEORRPFSOSIpilimumab+nivolumab(P3-CM214)4012.452.7Axitinib+pembrolizumab(P3-KN426)6115.747.2Cabozantinib+nivolumab(P3-CM9ER)5616.446.5Lenvatinib+pembrolizumab(P3-CLEAR)7123.953.7Belzutifan+cabozantinib7030.3NRZanzalintinib+nivolumab(Chahoud J.ASCO 2025,N=38)6318.5-Zanzalin

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根据报告的内容,全文主要探讨了肾细胞癌(RCC)的新型治疗策略,特别是HIF-2α抑制剂在治疗中的应用。以下是关键点: 1. RCC治疗挑战:传统化疗无效,存在肿瘤异质性,低频驱动突变,高频染色质重塑突变。 2. HIF-2α抑制剂与TKIs结合:如Belzutifan + Cabozantinib在1L和2L RCC中显示出良好的ORR(客观缓解率)和PFS(无进展生存期)。 3. 免疫治疗后的治疗选择:Belzutifan + Cabozantinib在1L和2L RCC中显示出ORR 30.3%和PFS NR。 4. HIF-2α抑制剂单药治疗:Casdatifan在2L RCC中显示出ORR 25%。 5. HIF-2α抑制剂与TKIs联合治疗:如Belzutifan + Lenvatinib在2L RCC中显示出ORR 46.9%和PFS 12.5个月。 6. 未来研究方向:探索HIF-2α抑制剂与其他TKIs或药物的联合治疗。
肾癌新疗法潜力大?" "免疫治疗后,肾癌治疗新选择?" 肾癌未来之路?"
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