Investigational Drug
Sacituzumab tirumotecan
TrialFetch AI Analysis
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Overview
Sacituzumab tirumotecan (sac-TMT; SKB264; MK-2870) is an investigational antibody–drug conjugate (ADC) being evaluated across multiple solid tumors. The most mature evidence comes from randomized studies in previously treated metastatic triple-negative breast cancer (TNBC) and EGFR-mutated non-small-cell lung cancer (NSCLC). Earlier-phase activity has also been reported in hormone-receptor-positive breast, urothelial, endometrial, ovarian, cervical, gastric and other cancers. (nature.com)
Mechanism of action
Sac-TMT consists of a humanized antibody targeting TROP2, a cell-surface protein frequently overexpressed by epithelial cancers, conjugated through a hydrolytically cleavable linker to KL610023, a belotecan-derived topoisomerase I inhibitor. Its average drug-to-antibody ratio is approximately 7.4. After TROP2 binding and internalization, KL610023 is released and inhibits topoisomerase I, causing DNA damage and tumor-cell death. (frontiersin.org)
Efficacy
- Metastatic TNBC: In the 263-patient phase 3 OptiTROP-Breast01 trial, sac-TMT improved median progression-free survival versus physician’s-choice chemotherapy: 6.7 vs 2.5 months (hazard ratio 0.32). Objective response rates were 45.4% vs 12.0%, and median response durations were 7.1 vs 3.0 months. At the interim overall-survival analysis, median survival was not reached with sac-TMT versus 9.4 months with chemotherapy (hazard ratio 0.53). (nature.com)
- EGFR-mutated NSCLC: In a randomized Chinese trial of 137 patients previously treated with an EGFR inhibitor and platinum chemotherapy, sac-TMT produced an objective response rate of 45%, compared with 16% for docetaxel. Median progression-free survival was 6.9 vs 2.8 months (hazard ratio 0.30), while 12-month overall survival was 73% vs 54%. (pubmed.ncbi.nlm.nih.gov)
- Other tumors: Preliminary single-arm studies have reported responses in urothelial cancer—confirmed response rates of 45.5% in second line and 26.3% in third or later lines—and in previously treated endometrial cancer, where the response rate was 34.1%**. These small, non-randomized cohorts require confirmation. (ascopubs.org)
Safety
Toxicity is predominantly hematologic. In the TNBC phase 3 trial, hematologic toxicity was the most common treatment-related adverse-event category. In an earlier 59-patient TNBC cohort, 57.6% experienced grade 3 or worse treatment-related events, most commonly decreased neutrophils (25.4%), decreased white-cell counts (23.7%), anemia (22.0%) and decreased platelets (16.9%); no treatment-related deaths, interstitial lung disease or grade 3 or worse diarrhea were reported. (nature.com)
In the randomized EGFR-mutated NSCLC study, grade 3 or worse treatment-related adverse events occurred in 56% of sac-TMT recipients versus 72% with docetaxel. Longer follow-up and broader international experience remain important for defining uncommon or delayed toxicities. (pubmed.ncbi.nlm.nih.gov)
Further reading
- Phase 3 OptiTROP-Breast01 trial in metastatic TNBC
- Randomized trial versus docetaxel in EGFR-mutated NSCLC
- Phase 2 TNBC results
- Preclinical mechanism and pharmacology
Last updated: Sep 2026
Active trials using Sacituzumab tirumotecan
Found 18 active trials using this drug:
TrialFetch AI summary: Adults with relapsed pure ovarian, fallopian tube, peritoneal, or endometriosis-associated clear cell carcinoma after platinum/taxane chemotherapy and exactly one prior immune checkpoint inhibitor–containing line receive sacituzumab tirumotecan alone or with pembrolizumab. Sacituzumab tirumotecan is a TROP2-directed antibody-drug conjugate delivering a topoisomerase I inhibitor; pembrolizumab blocks PD-1.
ClinicalTrials.gov ID: NCT07718854
TrialFetch AI summary: Patients with unresectable locally advanced or metastatic urothelial carcinoma progressing after anti-PD-(L)1 therapy, platinum chemotherapy, and enfortumab vedotin (or disitamab vedotin in China) are randomized to sacituzumab tirumotecan or investigator’s choice of paclitaxel, docetaxel, or vinflunine. Sacituzumab tirumotecan is a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT07419295
TrialFetch AI summary: Adults with advanced or metastatic KRAS G12C-mutated nonsquamous NSCLC that has progressed after 1–2 prior lines including platinum chemotherapy and PD-1/PD-L1 therapy, and who have not received prior KRAS-targeted therapy, receive calderasib, a KRAS G12C inhibitor, combined with either patritumab deruxtecan (HER3-directed ADC), sacituzumab tirumotecan (TROP2-directed ADC), or cetuximab (EGFR-directed antibody).
ClinicalTrials.gov ID: NCT07286149
TrialFetch AI summary: Adults with PD-L1 CPS ≥1 persistent, recurrent, or newly diagnosed metastatic cervical cancer who have not progressed after first-line pembrolizumab and platinum-taxane induction are randomized to maintenance pembrolizumab with or without sacituzumab tirumotecan; bevacizumab is optional in either arm. Sacituzumab tirumotecan is an investigational TROP2-targeted antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT07216703
TrialFetch AI summary: Adults with previously untreated, locally advanced unresectable or metastatic esophageal squamous cell carcinoma and ECOG performance status 0–1 receive pembrolizumab plus an investigational antibody–drug conjugate, with or without chemotherapy, or pembrolizumab plus mFOLFOX6. The investigational agents are ifinatamab deruxtecan (B7-H3–targeted) and sacituzumab tirumotecan (TROP2-targeted), both of which deliver topoisomerase I inhibitors.
ClinicalTrials.gov ID: NCT06780111
TrialFetch AI summary: Patients with advanced or recurrent mismatch repair–proficient endometrial carcinoma who do not progress after first-line pembrolizumab plus carboplatin and a taxane are randomized to maintenance pembrolizumab alone or with sacituzumab tirumotecan. Sacituzumab tirumotecan is an investigational TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06952504
TrialFetch AI summary: For patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer after six cycles of second-line carboplatin-based doublet chemotherapy, this study compares maintenance sacituzumab tirumotecan, with or without bevacizumab, against local standard-of-care maintenance with optional bevacizumab. Sacituzumab tirumotecan is an investigational TROP2-targeted antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06824467
TrialFetch AI summary: Adults with previously untreated, unresectable locally recurrent or metastatic triple-negative breast cancer and PD-L1 CPS <10 are randomized to sacituzumab tirumotecan alone, sacituzumab tirumotecan plus pembrolizumab, or physician’s-choice chemotherapy. Sacituzumab tirumotecan is an investigational TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06841354
TrialFetch AI summary: Adults with previously untreated, locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma without known HER2 positivity receive pembrolizumab plus fluoropyrimidine chemotherapy with or without sacituzumab tirumotecan. Sacituzumab tirumotecan is an investigational TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06469944
TrialFetch AI summary: For patients with unresectable locally advanced or metastatic HER2-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma that has progressed after one platinum/fluoropyrimidine-based regimen, this study compares sacituzumab tirumotecan plus paclitaxel with ramucirumab plus paclitaxel. Sacituzumab tirumotecan is an investigational TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06445972
TrialFetch AI summary: For adults with measurable recurrent or metastatic cervical cancer that progressed after one platinum-doublet regimen and prior anti-PD-1/PD-L1 therapy, this study compares second-line sacituzumab tirumotecan with physician’s choice of pemetrexed, tisotumab vedotin, topotecan, vinorelbine, gemcitabine, or irinotecan. Sacituzumab tirumotecan is a TROP2-targeted antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06459180
TrialFetch AI summary: This trial enrolls patients with previously treated unresectable or metastatic colorectal cancer, advanced pancreatic ductal adenocarcinoma, or advanced or unresectable biliary tract cancer; one biliary tract cohort also allows patients without prior systemic therapy. Patients receive sacituzumab tirumotecan, an investigational TROP2-targeted antibody–drug conjugate delivering a topoisomerase I inhibitor, alone or with fluorouracil/leucovorin or cisplatin/pembrolizumab.
ClinicalTrials.gov ID: NCT06428409
TrialFetch AI summary: For patients with EGFR-mutated advanced nonsquamous NSCLC that has progressed after EGFR tyrosine kinase inhibitor therapy, this trial compares sacituzumab tirumotecan, a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor, with carboplatin plus pemetrexed followed by pemetrexed maintenance.
ClinicalTrials.gov ID: NCT06305754
TrialFetch AI summary: Adults with previously untreated stage IV squamous NSCLC and ECOG 0–1 receive pembrolizumab plus carboplatin and paclitaxel or nab-paclitaxel; those without progression after four cycles are randomized to maintenance pembrolizumab with or without sacituzumab tirumotecan. Sacituzumab tirumotecan is an investigational TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06422143
TrialFetch AI summary: For patients with HR+/HER2− unresectable locally advanced or metastatic breast cancer that progressed after endocrine therapy including a CDK4/6 inhibitor, and who have not received chemotherapy for advanced disease, this trial compares sacituzumab tirumotecan alone or with pembrolizumab against physician’s-choice chemotherapy. Sacituzumab tirumotecan is a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor; pembrolizumab inhibits PD-1.
ClinicalTrials.gov ID: NCT06312176
TrialFetch AI summary: Adults with untreated metastatic squamous or nonsquamous NSCLC, PD-L1 TPS ≥50%, and ECOG performance status 0–1 are randomized to pembrolizumab alone or pembrolizumab plus sacituzumab tirumotecan. Sacituzumab tirumotecan is an investigational TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06170788
TrialFetch AI summary: Patients with previously treated unresectable or metastatic nonsquamous NSCLC harboring common EGFR mutations or selected other actionable alterations, after prior targeted therapy and platinum chemotherapy, are randomized to sacituzumab tirumotecan or docetaxel/pemetrexed. Sacituzumab tirumotecan is a TROP2-directed antibody–drug conjugate that delivers a topoisomerase I inhibitor.
ClinicalTrials.gov ID: NCT06074588
TrialFetch AI summary: Adults with unresectable locally advanced or metastatic esophageal squamous cell carcinoma progressing after one platinum- and PD-1/PD-L1–containing regimen receive investigator-selected paclitaxel or irinotecan, or investigational sacituzumab tirumotecan, a TROP2-directed antibody–drug conjugate delivering a topoisomerase I inhibitor. Arms combining pembrolizumab with the anti-ILT4 antibody MK-4830 and either chemotherapy or lenvatinib are no longer enrolling.
ClinicalTrials.gov ID: NCT05319730
