Early clinical antitumor activity of VRN101099 across diverse HER2-mutants in solid tumors
https://esmocongress.esmo.org
ESMO 2026
2026 年 10 月 23–27 日 · Madrid · 共 2740 条
HER2
★★★42 人 · 69 条 · 8 篇摘要
本事件热度走势
当前热度 11·可比范围峰值 13(10月25日 00:00)·近 24 小时可比范围变化 –·当前参与者 20
抗HER2治疗是靶向治疗的样板:HER2基因扩增与蛋白过表达见于25%至30%的乳腺癌,使肿瘤更具侵袭性;曲妥珠单抗联合化疗在转移性乳腺癌中将中位至疾病进展时间由4.6个月延长至7.4个月[2],在可手术HER2阳性早期乳腺癌的辅助治疗中同步联合化疗亦确立了获益[5]。分子层面,HER2富集亚型以HER2/磷酸化HER2/EGFR信号通路的特征性激活为标志[1];而在新辅助场景,pCR经汇总分析验证与EFS、OS相关,可作为长期获益的替代终点[6],这为解读会上另一条以pCR为终点的新辅助数据提供了参照。
本次ESMO26乳腺癌口头及优选论文环节的HER2主线落在HER2-low乳腺癌的ADC上:Barbara Pistilli就前三个摘要展开讨论,三者分别测试三种不同的HER2 ADC,却共享同一靶点、同一连接子、同一载荷类别。其中最受关注的是中国的TQB2102(双表位HER2 TOP1 ADC),在以HR+/HER2-low为主的转移性乳腺癌中报告PFS 16.4对比5.5个月、HR 0.29、p<0.01;发帖专家同时指出,双表位设计是否带来额外增益尚不清楚,HER2 TOP1赛道已相当拥挤且不乏优秀药物,HR+/HER2-转移性乳腺癌的ADC格局同样拥挤,最优序贯问题悬而未决。
同场另一条HER2相关读数偏阴性:一项汇总8项研究、2,529例患者的meta分析评估在紫杉类联合双HER2阻断的新辅助方案中加用卡铂,pCR率为62.2%对比61.7%,未见显著改善,所评估的临床亚组亦然。在pCR已被验证与长期转归相关的背景下[6],这提示双阻断时代常规加铂仍缺乏支持。neoHIP的讨论则显示免疫增敏的预测标志物尚未定型:pembro在ER+/HER2+人群中的获益仅见于高TIL或PD-L1+者,与IMpassion050中获益见于PD-L1-/HR+者的结果方向不同。
综合来看,TQB2102把抗HER2药物的作用范围从传统的扩增/过表达人群[2]推进到以HR+为主的HER2-low晚期乳腺癌;但局限同样清楚:该读数的样本量、试验分期与对照组具体方案在会议帖中未披露,双表位设计的增益存疑,而多种同类ADC之间的最优序贯、以及卡铂在当前新辅助治疗中的定位,都仍有待更成熟的数据回答。
- 1.Comprehensive molecular portraits of human breast tumours · Nature 2012
- 2.Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 · N Engl J Med 2001
- 3.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial · Lancet 2010
- 4.Gastric cancer · Lancet 2020
- 5.Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer · N Engl J Med 2005
- 6.Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis · Lancet 2014
Health-related quality of life from HER2CLIMB-05: A phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as 1L maintenance therapy for HER2+ mBC
https://esmocongress.esmo.orgSafety, social costs and quality of life (QOL) in HER2-positive (HER2+) breast cancer (BC) patients (pts) treated with pertuzumab + trastuzumab fixed-dose combination subcutaneous (PT FDC SC): The PERTURB study
https://esmocongress.esmo.orgA global, interventional, open-label trial of trastuzumab deruxtecan (T-DXd)–based therapy in first-line HER2-positive metastatic breast cancer: DESTINY-Breast Guide
https://esmocongress.esmo.orgEfficacy and safety of atirmociclib (ATI) + fulvestrant (FUL) in patients (pts) with HR+/HER2– advanced/metastatic breast cancer (mBC) who progressed on prior CDK4/6 inhibitor (CDK4/6i) in a randomized phase 2 study (FOURLIGHT-1)
https://esmocongress.esmo.orgGene-expression profiling of HR+/HER2- breast cancers arising in germline BRCA1/2 mutation carriers
https://esmocongress.esmo.orgOverall survival from the phase 3 postMONARCH trial of abemaciclib + fulvestrant vs placebo + fulvestrant for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor + endocrine therapy
https://esmocongress.esmo.orgTQB2102, a novel HER2 bispecific antibody-drug conjugate, combined with bemotrizumab with or without capecitabine as first-line therapy for HER2-positive advanced gastric/gastroesophageal junction cancer: A phase II study
https://esmocongress.esmo.orgPaolo Tarantino@PTarantinoMD 视角:新型 HER2 ADC 不断提高 HER2 低表达乳腺癌的治疗标准。 @FraSchettMDPhD #ESMO26
Ingo Hartung@HartungIngo dr_yakupergun@dr_yakupergun Sara Tolaney@stolaney1 Sara Tolaney@stolaney1 Matteo Lambertini, MD PhD@matteolambe 超级 @BarbaraPistill2 在 #ESMO26 的口头摘要 #BreastCancer 会议上关于 HER2 低表达患者 ADC 的精彩讨论 👏👏👏👏 @OncoAlert @myESMO
Memorial Sloan Kettering Cancer Center@MSKCancerCenter AACR 2026 现场信号@ Paolo Tarantino@PTarantinoMD AACR 2026 现场信号@ AACR 2026 现场信号@ OncoAlert@OncoAlert Yakup Ergün@dr_yakupergun 在 HR+/HER2− mBC 领域,ADC 竞争日益激烈,多项阳性试验涌现,但关于最佳序贯治疗的问题仍未解答。 来自 Dr. Babrara Pastilli 在 #ESMO26 上的精彩讨论
Aya Mohamed | MSc, MD 🎗@Dr_Oncologista Elisa Agostinetto@ElisaAgostinett Mario Balsa@MarioBalsaMD 引用@🚨 #ESMO26 GI Cancer: Top Ten by @OncoAlert 🧬 From organ preservation in dMMR rectal and gastric cancer to RAS(ON) inhibition in pancreatic cancer and bispecifics in biliary tract cancer, our faculty picked the must-know GI abstracts from Madrid 👇 #GICancer #CRCSM @CathyEngMD, @BenWestphalen, @graokane, @NiuSanford, @GillSharlene, @pashtoonkasi, @DrVilmaPBarcia, @Erman_Akkus, @GIMedOnc, @UOzkerim, @MarioBalsaMD, @p_ciracimd, @DraMartinezLago, @DaisukeKotani, @Aiims1742, @ARosen380, @realbowtiedoc, @KoheiShitara , @pashtoonkasi , @GillSharlene
Antonio Giordano, MD PhD@antgiorda HR+/Her2- 早期乳腺癌中下一个严重的未满足需求。如何挽救 MRD 阳性患者? #ESMO26
AACR 2026 现场信号@ 萨拉特·钱达拉帕蒂博士在 #AACR26 分享了关于抗 HER2 ADC 的深刻研究
COR2ED@COR2EDMedEd Matteo Lambertini, MD PhD@matteolambe Elisa Agostinetto@ElisaAgostinett Gaia Griguolo@GaiaGriguolo Vilma P. Barcia MD, PhD, MSc@DrVilmaPBarcia Yakup Ergün@dr_yakupergun Mitsuo Terada, MD, PhD@乳腺科医@MamMa_mimumemo 高齢者のHR+HER2-、T1、grade 1-2で、Bp後に放射線、薬物療法なしでの経過観察。
Abeid Athman (Omar).@bin_abeid @stolaney1 在 @Medscape 全球肿瘤学会议上展示 1L HER2+ MBC 的选择 #ESMO2026 @myESMO @OncoAlert
Bristol Myers Squibb@bmsnews #MEDIA: 宣布在 #ESMO26 上公布针对某些 HR+/HER2- 乳腺癌成人患者的研究性治疗的 III 期试验结果。 https://bit.ly/4siOO3r
Elisa Agostinetto@ElisaAgostinett GEICAM - Cáncer de mama@GEICAM Philippe Aftimos, MD @aftimosp