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 2840 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
参与者计数20
热度走势
深度解读
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。
参考来源
- 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
证据
1766RO
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.org1780P
Safety, 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.org1795TIP
A 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.org1842O
Efficacy 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.org1844P
Gene-expression profiling of HR+/HER2- breast cancers arising in germline BRCA1/2 mutation carriers
https://esmocongress.esmo.org1RO
Overall 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.org2876RO
TQB2102, 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.org现场
Mitsuo Terada, MD, PhD@乳腺科医@MamMa_mimumemo Dr Riyaz Shah@DrRiyazShah DESTINY-Lung 04；#ESMO26 更新；PRO’s> 一些信号支持研究性药物。支持一线使用 her2 靶向治疗。不要对此过度解读
AACR 2026 现场信号@ Dana-Farber’s Breast Oncology Center@DFCI_BreastOnc Kristina Jankovic, MD@JankovicK Mitsuo Terada, MD, PhD@乳腺科医@MamMa_mimumemo ET-FES試験。ERを見るPET(FES)を使ってER+/HER2- mBCでのFES-PETとFDG-PETでのheterogeneity評価。
Gustavo Werutsky@GustavoWerutsky Evandro de Azambuja, MD, PhD@E_de_Azambuja TDXD在HER2低表达ER+早期乳腺癌中的活性较低 #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO
Kelly Anderson@kelly_archives HER2阳性疾病领域前景喜人。拓展不受PD-L1状态限制的有效一线治疗选择，可能真正改变胃食管腺癌的诊疗格局。#AACR26 #EndCancer
Yuhei YAMAGUCHI@yymgcmd 引用@Moving beyond one-size fits all in HER2+ BC involves understanding trends. We explored a database of ~15.000 pts treated with neoadjuvant pertuzumab based NAT. We found that the T2N0 population (DB11-ineligible) is progressively expanding and has favorable 3y DRFS (96%) with SoC.
Evandro de Azambuja, MD, PhD@E_de_Azambuja 基线 HER2 Pet 可作为排除 TDXD 在 MBC 中应答的有力指标 #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO
ChiaraMolinelli@ChiaraMolinelli @ALEDIGNUS12 带来了一场精彩的报告：可通过 18F-FES PET 评估 ER+/HER2− MBC 的全身 ER 异质性，且其具有重要的预后作用。#ESMO2026
Mitsuo Terada, MD, PhD@乳腺科医@MamMa_mimumemo OncLive.com@OncLive Jazz Pharmaceuticals@JazzPharma OncologyEducation@OncEd OncologyEducation@OncEd OncologyEducation@OncEd Gustave Roussy@GustaveRoussy Dana-Farber’s Breast Oncology Center@DFCI_BreastOnc