Sacituzumab tirumotecan (Sac-TMT) + pembrolizumab (Pembro) in post-platinum advanced mismatch repair proficient (pMMR) endometrial cancer (EC)
https://esmocongress.esmo.org
ESMO Congress 2026
October 23–27, 2026 · Madrid · 2652 items
sacituzumab
12 people · 15 posts · 4 abstracts
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Heat now 5·Peak in the comparable set 6 (Oct 24 19:00)·Change over 24h in the comparable set –·Participants now 8
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Deep dive
Sacituzumab govitecan is a Trop-2-directed antibody-drug conjugate (ADC) that couples a humanized antibody to the topoisomerase I inhibitor SN-38 via a cleavable linker, delivering at a high drug-antibody ratio of 7.6:1 and releasing SN-38 in its active, non-glucuronidated form [2][5]. The evidence base for this asset class is established: in the phase 3 ASCENT trial in relapsed or refractory metastatic triple-negative breast cancer, median PFS was 5.6 months versus 1.7 months with physician's-choice single-agent chemotherapy [1]; in the phase 3 TROPiCS-02 trial in previously treated HR+/HER2- metastatic breast cancer, the protocol-specified final overall survival analysis has also been reported [4]. In urothelial carcinoma, TROPHY-U-01 Cohort 1 enrolled patients progressing after platinum and checkpoint inhibitors, with a centrally reviewed ORR of 27% and median duration of response of 7.2 months [3].
Two pieces of information related to this drug emerged at ESMO26. The main story is the interim data from TROPHY-U-01 Cohort 7: sacituzumab govitecan + enfortumab vedotin (EV) + zimberelimab in treatment-naive metastatic urothelial cancer (N=21), with an ORR of 81% (including 14% CR), median DOR of 16.7 months, median PFS of 19.3 months, and median OS not reached; grade ≥3 treatment-related AEs were 52%, and 33% of patients discontinued at least one agent. The other is a 4Sight paired-biopsy multi-omic study (n=26): after T-DXd, HER2 decreased in 57% but none became HER2-null; after SG, there was no consistent TROP2 downregulation (5/14 up, 3/14 down); more than 50% showed increased efflux transporters (ABCB1, ABCC1), with functional validation demonstrating reduced payload accumulation and ADC sensitivity, suggesting ADC resistance is driven by complex adaptations beyond target modulation.
Relative to prior knowledge, Cohort 7 moves SG in urothelial carcinoma from later-line monotherapy after platinum and checkpoint inhibitor failure (ORR 27%) [3] to the first-line setting, combining it with the Nectin-4-directed EV and the PD-1 inhibitor zimberelimab as dual ADC plus IO, with markedly higher early efficacy and a longer PFS; the on-site posts also raised the key question of whether the added efficacy justifies the toxicity over EV + pembrolizumab. The paired-biopsy study suggests that tackling ADC resistance requires thinking beyond target expression modulation, toward drug efflux, trafficking, and cellular stress responses.
Limitations: Cohort 7 is a single-arm interim result with N=21, OS is immature, grade ≥3 treatment-related AEs and discontinuation rates are not low, and no comparative data versus EV + pembrolizumab are available yet; the resistance-mechanism study included only 26 patients, and its conclusions await validation in larger samples.
References
- 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
Evidence
35P
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.org4739RO
Sacituzumab 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.org4742O
Sacituzumab 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.orgFloor
Daniel Castellano@cdanicas OncoAlert@OncoAlert OncoAlert 4Sight Abstracts to be Presented at #ESMO26
★★★Same topic sacituzumab · 12 peoplegovitecanHER2TROP2#BREASTCANCER1850 views9 likes6 reposts0 repliesIcro Meattini@Icro_Meattini Same topic sacituzumab · 12 peoplegovitecan#RADIOTHERAPY#BREASTCANCER277 views16 likes7 reposts0 repliesJulian Chavarriaga@chavarriagaj #ESMO26 Can two ADCs + IO push response rates even higher in 1L metastatic urothelial cancer?
Same topic sacituzumab · 12 peoplegovitecanenfortumabzimberelimabpembrolizumab330 views6 likes3 reposts1 replyDra. 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 More ADC + IO data at #ESMO26!
OncLive.com@OncLive Martin ZapataLaguado@zapatalaguadomd Martin ZapataLaguado@zapatalaguadomd MBC Advocate@MBCadvocate OncoAlert@OncoAlert Same topic sacituzumab · 12 peoplegovitecanenfortumabFGFR3#OAONTHEGO#UROTHELIALCANCER#BLADDERCANCER101 views0 likes0 reposts0 repliesmp.weixin.qq.comPick Kelun-Biotech TROP2 ADC Sacituzumab Tirumotecan Posts Final TNBC OS, Median OS 14.7 Months
At the ESMO congress, Kelun-Biotech's TROP2 ADC sacituzumab tirumotecan (SKB264) presented the final overall survival analysis of a China trial in second-line and later advanced triple-negative breast cancer. With 29.4 months of follow-up, median OS was 14.7 months versus 9.9 months with chemotherapy, HR=0.60; after adjusting for subsequent ADC treatment as a confounder, HR=0.55.
Why it matters: The brief gives median OS 14.7 months with HR=0.60, plus HR=0.55 after adjusting for subsequent ADC confounding.
BioSpacePick ESMO 2026: Merck’s Kelun-partnered ADC hits the ‘Goldilocks zone,’ VP says
A Merck vice president said sac-TMT, the ADC partnered with Kelun-Biotech, uses an irreversible linker that keeps the drug stable in the blood until it reaches the tumor, with payload release in what he called the 'Goldilocks zone.' The original contrasts this with the reversible linkers of Trodelvy and Datroway, noting that premature payload release can cause anemia and neutropenia, while release that is too slow may also affect other TROP2-expressing tissues.
Why it matters: The original contrasts sac-TMT's irreversible linker with the reversible linkers of Trodelvy and Datroway, showing differing release mechanisms for the same TROP2 target.
Same topic sacituzumab · 12 peopleNo engagement yet