Sacituzumab tirumotecan (Sac-TMT) + pembrolizumab (Pembro) in post-platinum advanced mismatch repair proficient (pMMR) endometrial cancer (EC)
https://esmocongress.esmo.org
ESMO 2026
2026 年 10 月 23–27 日 · Madrid · 共 2740 条
sacituzumab
12 人 · 15 条 · 4 篇摘要
本事件热度走势
当前热度 5·可比范围峰值 6(10月24日 19:00)·近 24 小时可比范围变化 –·当前参与者 8
戈沙妥珠单抗(sacituzumab govitecan)是靶向 Trop-2 的抗体偶联药物(ADC),通过可裂解连接子将人源化抗体与拓扑异构酶 I 抑制剂 SN-38 偶联,以高药物抗体比 7.6:1 递送、且以非葡萄糖醛酸化的活性形式释放 SN-38 [2][5]。这一资产的类别证据已经站住:在复发难治转移性三阴性乳腺癌的 III 期 ASCENT 试验中,中位 PFS 为 5.6 个月,优于医生选择单药化疗的 1.7 个月 [1];在既往多线治疗的 HR+/HER2- 转移性乳腺癌 III 期 TROPiCS-02 中,也已报告方案预设的最终总生存分析 [4]。在尿路上皮癌,TROPHY-U-01 队列 1 纳入铂类与免疫检查点抑制后进展的患者,经中央评估的 ORR 为 27%,中位缓解持续时间 7.2 个月 [3]。
本次 ESMO26 现场有两条与该药相关的信息。主线是 TROPHY-U-01 队列 7 的中期数据:在既往未经治疗的转移性尿路上皮癌(N=21)中评估 sacituzumab govitecan + enfortumab vedotin(EV)+ zimberelimab 三联方案,ORR 为 81%(其中 CR 14%),中位 DOR 16.7 个月,中位 PFS 19.3 个月,中位 OS 未达到;≥3 级治疗相关不良事件为 52%,33% 的患者停用至少一种药物。另一条是 4Sight 的配对活检多组学研究(n=26):T-DXd 治疗后 57% 的患者 HER2 表达下降但无一变为 HER2-null;SG 治疗后 TROP-2 无一致下调(14 例中 5 例上调、3 例下调);超过 50% 的患者外排转运体(ABCB1、ABCC1)升高,功能验证显示载荷蓄积与 ADC 敏感性降低,提示 ADC 耐药由靶点调控之外的复杂适应驱动。
相对已有认识,队列 7 把 SG 在尿路上皮癌的位置从铂类与免疫治疗失败后的单药后线(ORR 27%)[3] 前移到一线,并与靶向 Nectin-4 的 EV 及 PD-1 抑制剂 zimberelimab 组成双 ADC 加免疫的组合,早期疗效数字显著抬升、PFS 明显延长;现场帖也点出关键问题——相比 EV + pembrolizumab,这种叠加的疗效是否足以抵偿其毒性。而配对活检研究则提示,应对 ADC 耐药的思路需超越靶点表达调节本身,转向外排、转运与细胞应激等通路。
局限在于:队列 7 为 N=21 的单臂中期结果,OS 尚未成熟,≥3 级治疗相关不良事件与停药比例不低,且与 EV + pembrolizumab 的比较尚未有数据;耐药机制研究仅 26 例,结论有待更大样本验证。
- 1.Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer · N Engl J Med 2021
- 2.Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer · N Engl J Med 2019
- 3.TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors · J Clin Oncol 2021
- 4.Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial · Lancet 2023
- 5.Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC) · Oncotarget 2015
- 6.Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial · Ann Oncol 2021
Comparative effectiveness of trastuzumab deruxtecan versus sacituzumab govitecan in HER2-negative metastatic breast cancer: A real-world analysis with propensity score matching
https://esmocongress.esmo.orgSacituzumab Tirumotecan (Sac-TMT) + Pembrolizumab (Pembro) for Locally Advanced or Metastatic Urothelial Carcinoma (la/mUC): Results From a Phase 2 Study (2870-002/SKB264-II-06)
https://esmocongress.esmo.orgSacituzumab Govitecan (SG) Combined With Enfortumab Vedotin (EV) and Zimberelimab (ZIM) in Treatment-Naive Metastatic Urothelial Cancer (mUC): Interim Results From Phase 1b TROPHY-U-01 Cohort 7
https://esmocongress.esmo.orgDaniel Castellano@cdanicas OncoAlert@OncoAlert Icro Meattini@Icro_Meattini Julian Chavarriaga@chavarriagaj Dra. María Natalia Gandur Quiroga@nataliagandur 引用@🧬 Can triplet combinations improve outcomes in advanced urothelial cancer? And how do we manage their toxicity? #OAOnTheGo Series In this new OncoAlert video live from the floor at #ESMO26, Dr. Sara Coca Membribes, @scocmem medical oncologist and genitourinary (GU) clinical research fellow at the Barts Cancer Institute🇬🇧 , discusses the results of TROPHY Cohort 7, evaluating sacituzumab govitecan (SG), enfortumab vedotin (EV), and a PD-1 inhibitor. 🔬 Key takeaways: ▪️ All 18 patients achieved tumor shrinkage, with durable responses. ▪️ No treatment-related deaths were reported. ▪️ Approximately 60% of patients experienced Grade 3 adverse events. ▪️ G-CSF support was mandatory in the study. With several trials exploring frontline triplet combinations using different ADCs, payloads, and targeted therapies—including FGFR3 inhibition in the FORAGER trial—the challenge is not only achieving efficacy, but also managing toxicity without compromising treatment outcomes. 🎥 Watch Dr. Sara Coca Membribes' video for her insights into these promising strategies and why toxicity management is essential for the future of combination therapy. #UrothelialCancer #BladderCancer Pinging Our Faculty @DrChoueiri, @tompowles1, @apolo_andrea, @neerajaiims, @montypal, @Silke_Gillessen, @AOmlin, @brian_rini, @PGrivasMDPhD, @TiansterZhang, @amerseburger, @DrDanielHeng, @HHammersMD, @scocmem, @AndreaNecchi, @AmandaNizamMD, @drenriquegrande, @nataliagandur, @AlbigesL, @cdanicas, @declangmurphy, @seanmmcbride, @shilpaonc, @DrRanaMcKay, @scserendipity1, @DrYukselUrun, @ravikanesvaran, @BraunMDPhD, @EfstathiouEleni, @mzugman, @crisbergerot, @niklas_kluemper @Markuseckstein3
Elisabetta Bonzano MD, PhD@to_be_elizabeth 引用@🧬 Can triplet combinations improve outcomes in advanced urothelial cancer? And how do we manage their toxicity? #OAOnTheGo Series In this new OncoAlert video live from the floor at #ESMO26, Dr. Sara Coca Membribes, @scocmem medical oncologist and genitourinary (GU) clinical research fellow at the Barts Cancer Institute🇬🇧 , discusses the results of TROPHY Cohort 7, evaluating sacituzumab govitecan (SG), enfortumab vedotin (EV), and a PD-1 inhibitor. 🔬 Key takeaways: ▪️ All 18 patients achieved tumor shrinkage, with durable responses. ▪️ No treatment-related deaths were reported. ▪️ Approximately 60% of patients experienced Grade 3 adverse events. ▪️ G-CSF support was mandatory in the study. With several trials exploring frontline triplet combinations using different ADCs, payloads, and targeted therapies—including FGFR3 inhibition in the FORAGER trial—the challenge is not only achieving efficacy, but also managing toxicity without compromising treatment outcomes. 🎥 Watch Dr. Sara Coca Membribes' video for her insights into these promising strategies and why toxicity management is essential for the future of combination therapy. #UrothelialCancer #BladderCancer Pinging Our Faculty @DrChoueiri, @tompowles1, @apolo_andrea, @neerajaiims, @montypal, @Silke_Gillessen, @AOmlin, @brian_rini, @PGrivasMDPhD, @TiansterZhang, @amerseburger, @DrDanielHeng, @HHammersMD, @scocmem, @AndreaNecchi, @AmandaNizamMD, @drenriquegrande, @nataliagandur, @AlbigesL, @cdanicas, @declangmurphy, @seanmmcbride, @shilpaonc, @DrRanaMcKay, @scserendipity1, @DrYukselUrun, @ravikanesvaran, @BraunMDPhD, @EfstathiouEleni, @mzugman, @crisbergerot, @niklas_kluemper @Markuseckstein3
Julian Chavarriaga@chavarriagaj David H Aggen, MD PhD@Dr_Aggen OncLive.com@OncLive Martin ZapataLaguado@zapatalaguadomd Martin ZapataLaguado@zapatalaguadomd MBC Advocate@MBCadvocate OncoAlert@OncoAlert 中文产业新闻精选 科伦博泰TROP2 ADC芦康沙妥珠单抗公布TNBC三期最终OS分析,中位OS 14.7个月
科伦博泰TROP2 ADC芦康沙妥珠单抗(SKB264)在ESMO大会公布2L+晚期三阴性乳腺癌中国III期最终OS分析,随访29.4个月,中位OS 14.7个月对比化疗9.9个月,HR=0.60;调整后线ADC治疗干扰后HR=0.55。
推荐理由:原文给出中位OS 14.7个月与HR=0.60,并附调整后线ADC干扰后的HR=0.55,读者可据此直接比较该药在TNBC二线及以上治疗中的获益幅度。
BioSpace精选 ESMO 2026:默沙东副总裁称,与科伦博泰合作的sac-TMT ADC处于“恰到好处”区间
默沙东副总裁称,与科伦博泰合作的sac-TMT采用不可逆连接子,可在血液中保持稳定直至到达肿瘤,释放表现处于其所说的“恰到好处”区间。原文将其与Trodelvy、Datroway的可逆连接子对照,并指出载荷过早释放可能引发贫血和中性粒细胞减少,释放过慢也可能影响其他表达TROP2的组织。
推荐理由:原文将sac-TMT的不可逆连接子与Trodelvy、Datroway的可逆连接子对照,呈现相同TROP2靶点下的释放机制差异。