HERTHENA-Lung01：HER3-DXd / Patritumab Deruxtecan 用于 EGFR-TKI + 铂化疗后
类型: II期临床试验 / ADC 发表日期: 2023-09-10 入库日期: 2026-05-21 来源: PubMed / Journal of Clinical Oncology 标签: EGFR L858R, HER3-DXd, Patritumab deruxtecan, ADC, 奥希替尼后, 铂化疗后
Citation
Yu HA, et al. HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated Non-Small-Cell Lung Cancer After EGFR Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. Journal of Clinical Oncology. 2023. PMID: 37689979. DOI: 10.1200/JCO.23.01476
ClinicalTrials.gov: NCT04619004
Why it matters for mom
Mom has already received osimertinib plus platinum/pemetrexed-style treatment. HER3-DXd is directly relevant as a post-EGFR-TKI, post-platinum antibody-drug conjugate strategy, though access depends on approvals/trials and toxicity tolerance.
Practical takeaways
- This is an ADC option to track for later-line EGFR-mutant NSCLC.
- It is not selected by a classic resistance mutation like MET amplification; HER3 expression is common in EGFR-mutant NSCLC.
- Key risks to discuss for deruxtecan ADCs include interstitial lung disease/pneumonitis and marrow suppression.
⚠️ 重大更新 (2025-05 / 2026-05)
HER3-DXd 开发已终止。 2025年5月，第一三共与默沙东撤回了patritumab deruxtecan的生物制剂许可申请（BLA），因为确证性III期HERTHENA-Lung02试验未达到OS主要终点。第一三共2026年5月Q4财报电话会议确认HER3-DXd"在EGFR突变肺癌领域未显示出阳性结果"，上市时间表已被修改（无明确新目标）。第一三共已将HER3-DXd剔除其2030年肿瘤营收增长计划。
安全性问题加重失败：2026年ASCO期间公布的III期数据显示，58%患者出现≥3级TRAEs，共报告14例ILD病例（其中2例死于ILD）。加上I-DXd（B7-H3 ADC）近期因5级ILD发生率超标被FDA部分临床暂停，Daiichi Sankyo的DXd ADC平台安全性正面临监管审视。
来源: Daiichi Sankyo FY2026 Q4 earnings call (2026-05-11); BioSpace "Daiichi emerges from bruising 2 years" (2026-05-20); 36kr 行业分析 (2026-05-21); Targeted Oncology ASCO 2026 preview (2026-05-21).
实践影响
- HER3-DXd 不应再被视为妈妈的可行后线选择。
- 后线TROP2 ADC替代方案：Sac-TMT（中国已获批，已入医保）、Dato-DXd（美国加速批准，TNBC已获常规批准）。
- 国产HER3 ADC替代：恒瑞SHR-A2009 III期阳性（PFS显著延长，见2026-05-19条目），可能成为中国患者的HER3 ADC新选择。
- 这一结果提示EGFR突变NSCLC的ADC开发需要更精准的生物标志物选择和更好的安全性管理。
Questions for doctors
Is HER3-DXd available through trial, compassionate access, or approved channels in the treating region?→ 已不适用。- 替代方案（Sac-TMT、Dato-DXd等TROP2 ADC）在妈妈的临床情境中如何评估？
- Would mom's marrow reserve and lung status make an ADC too risky?