Sacituzumab Tirumotecan Meets PFS End Point as 1L Option in Advanced TNBC

The TROP2-directed antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) met its primary end point of progression-free survival (PFS) as a first-line treatment for patients with unresectable locally recurrent or metastatic triple-negative breast cancer (TNBC), according to data from a prespecified interim analysis of the phase 3 OptiTROP-Breast03 trial (NCT06279364) in a press release from Sichuan Kelun-Biotech Biopharmaceutical.¹

An Independent Data Monitoring Committee (IDMC) concluded that sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS compared with investigator's choice of chemotherapy. Overall survival (OS) data remain immature, though a positive trend was observed. The safety profile was consistent with that seen in prior studies, with no new signals identified.

This result marks the first registrational phase 3 study of sac-TMT to demonstrate a positive outcome in the first-line TNBC setting—a population with limited approved options, particularly among patients with PD-L1–negative disease.

OptiTROP-Breast 03 Topline Data

At the prespecified interim analysis, sac-TMT monotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS compared with investigator's choice of chemotherapy. Follow-up will continue per protocol, and OS will be evaluated in subsequent prespecified analyses.

Trial Background

OptiTROP-Breast03 is a randomized, open-label, multicenter phase 3 clinical study designed to evaluate the efficacy and safety of sac-TMT vs investigator's choice of chemotherapy in patients with unresectable recurrent or metastatic TNBC who have not received prior systemic therapy for advanced disease. The trial enrolled 2 patient populations with limited existing treatment options: those with programmed death ligand 1 (PD-L1)–negative expression and those with PD-L1–positive expression who relapsed after prior anti-PD-(L)1 inhibitor therapy in the early-stage setting. The 2 independent primary end points of the study are PFS and OS.

The drug itself is a novel anti-TROP2 human ADC developed with a bifunctional linker that connects the anti-TROP2 monoclonal antibody sacituzumab irreversibly to a belotecan-derivative topoisomerase I inhibitor payload. The construct carries a drug-to-antibody ratio (DAR) of 7.4. Upon binding to TROP2 on tumor cell surfaces, sac-TMT is endocytosed and releases its payload intracellularly, inducing DNA damage, cell-cycle arrest, and apoptosis. The membrane-permeable payload KL610023 also enables a bystander effect, allowing cytotoxic activity in adjacent tumor cells.

Prior Evidence Supporting Sac-TMT in TNBC

The phase 3 OptiTROP-Breast02 trial (NCT06081959) demonstrated a 65% reduction in the risk of disease progression or death with sac-TMT vs chemotherapy (HR, 0.35; 95% CI, 0.26-0.48; P <.0001) among patients with previously treated, locally advanced or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer, data that were presented at the European Society for Medical Oncology (ESMO) Congress 2025. At a median follow-up of 7.4 months, the median PFS was 8.3 months with sac-TMT compared with 4.1 months with chemotherapy. An interim OS analysis also showed a positive trend favoring sac-TMT (HR, 0.33; 95% CI, 0.18-0.61).

Next Steps

Based on these results, the company plans to engage with the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) to discuss the regulatory pathway for sac-TMT in this indication.

Of note, the global phase 3 TroFuse-011 trial (NCT06841354), is evaluating sac-TMT alone or in combination with pembrolizumab (Keytruda) as first-line treatment specifically for patients with PD-L1 combined positive score of less than 10 who have TNBC and remains ongoing.

References

1. Kelun-Biotech announces phase III trial of sacituzumab tirumotecan (sac-TMT) versus chemotherapy as first-line treatment for advanced TNBC met primary endpoint of PFS. News release. Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.; May 21, 2026. Accessed May 22, 2026. https://tinyurl.com/ywuycu47
2. Study of SKB264 for locally advanced, recurrent or metastatic TNBC (OptiTROP-Breast03). ClinicalTrials.gov. Updated May 8, 2026. Accessed May 22, 2026. https://tinyurl.com/565kcdyd
3. Li M. Sacituzumab tirumotecan (sac-TMT) vs investigator's choice of chemotherapy (ICC) in previously treated locally advanced or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer (BC): results from the randomized, multi-center phase 3 OptiTROP-Breast02 study. Presented at: ESMO 2025 Congress; October 17-20, 2025; Berlin, Germany. Abstract LBA23.