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 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 with findings 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-Breast03 Top-Line 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 PD-L1–negative expression and those with PD-L1–positive expression who experienced relapse 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 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) findings 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–positive, HER2-negative breast cancer, data that were presented at the European Society for Medical Oncology 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 of China's National Medical Products Administration 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. A study of SKB264 versus investigator's choice chemotherapy in patients with unresectable recurrent or metastatic triple-negative breast cancer. 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. Abstract presented at: European Society for Medical Oncology Congress 2025; October 17-20, 2025; Berlin, Germany. Abstract LBA23.