Sacituzumab Tirumotecan Earns Approval in China in Pretreated Advanced TNBC

The TROP2-directed antibody drug conjugate (ADC) sacituzumab tirumotecan (formerly SKB264/MK-2870) has been approved by China’s National Medical Products Administration (NMPA) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least 2 prior systemic therapies, including at least 1 in the advanced or metastatic setting.¹

Sacituzumab tirumotecan is the first TROP2-directed ADC and the first ADC developed in China that is fully approved for marketing in the country.

The regulatory decision was supported by findings from the phase 3 OptiTROP-Breast01 study (NCT05347134); data from the trial presented during the 2024 ASCO Annual Meeting demonstrated that patients who received sacituzumab tirumotecan (n = 130) achieved a median progression-free survival (PFS) per blinded independent central review (BICR) of 5.7 months (95% CI, 4.3-7.2) compared with 2.3 months (95% CI, 1.6-2.7) among patients who received investigator’s choice of chemotherapy (n = 133; HR, 0.31; 95% CI, 0.22-0.45; P < .00001).² Additionally, patients with high TROP2 expression (HR, 0.29; 95% CI, 0.19-0.46) and those with low/medium TROP2 expression (HR, 0.35; 95% CI, 0.21-0.56) achieved a significant PFS benefit with sacituzumab tirumotecan vs chemotherapy.

“It is a great pleasure to share with you the important milestone moment of the successful approval and launch of sacituzumab tirumotecan in China, which is a significant achievement of Kelun-Biotech's years of deep-rooted source innovation,” Micheal Ge, PhD, director of the National Engineering Research Center for Biotargeted Drug, president, and chief executive officer of Kelun-Biotech, stated in a news release.¹ “As the company's first proprietary TROP2 ADC innovative drug, the successful launch of sacituzumab tirumotecan officially opens up a new pattern for the treatment of patients with [second line and beyond] advanced TNBC.”

OptiTROP-Breast01 was an open-label study that enrolled patients with locally recurrent or metastatic TNBC whose disease relapsed following or was refractory to 2 or more prior chemotherapy regimens for unresectable, locally advanced, or metastatic disease.² Patients were allowed to have received taxanes in any setting. One prior therapy in the neoadjuvant or adjuvant setting was permitted if disease progression occurred during treatment or within 12 months after treatment discontinuation.

Patients were randomly assigned 1:1 to receive intravenous sacituzumab tirumotecan at a dose of 5 mg/kg every 2 weeks or physician’s choice of chemotherapy with eribulin, capecitabine, gemcitabine, or vinorelbine. Patients were stratified by number of prior lines of therapy (2-3 vs >3) and presence of liver metastases (yes vs no). Treatment in both arms continued until disease progression, unacceptable toxicity, or other reasons for discontinuation.

The primary end point was PFS by BICR. Secondary end points included overall survival (OS), investigator-assessed PFS, overall response rate (ORR), duration of response (DOR), and safety.

Additional findings from OptiTROP-Breast01 showed that the median OS at the interim OS analysis in the investigational arm was not yet reached (NR; 95% CI, 11.2-not evaluable) compared with 9.4 months (95% CI, 8.5-11.7) in the chemotherapy arm (HR, 0.53; 95% CI, 0.36-0.78; P = .0005). The 12-month OS rates were 57.8% vs 35.2%, respectively. The ORRs were 45.4% vs 12.0%, respectively, and the respective median DORs were 7.1 months vs 3.0 months (HR, 0.50; 95% CI, 0.22-1.13).

In terms of safety, all patients in the sacituzumab tirumotecan arm experienced a treatment-related adverse effect (TRAE) compared with 96.2% of patients in the chemotherapy arm. Patients in both arms experienced grade 3 or higher TRAEs (57.7% vs 56.8% for sacituzumab tirumotecan and chemotherapy, respectively), serious TRAEs (20.8% vs 12.9%), as well as TRAEs associated with treatment discontinuation (1.5% vs 1.5%), dose reduction (25.4% vs 15.9%), and dose interruption (51.5% vs 40.2%). One patient (0.8%) in the investigational arm experienced a TRAE resulting in death. The median treatment duration was 15.4 weeks (range, 2.0-44.0) and 8.6 weeks (range, 1.0-40.7), respectively.

“We expect that [sacituzumab tirumotecan’s] excellent clinical efficacy and safety results will significantly enhance the clinical benefits and improve the quality of life of patients with advanced TNBC,” Ge added in the news release.¹ “In the future, we will continue to explore the clinical value of sacituzumab tirumotecan in other indications, maximize the market potential of sacituzumab tirumotecan, and satisfy the clinical needs of patients nationwide.”

References

1. Kelun-Biotech’s TROP2 ADC sacituzumab tirumotecan (sac-TMT, 佳泰莱) approved for marketing by NMPA Of China for 2L+ advanced or metastatic TNBC. News release. Sichuan Kelun-Biotech Biopharmaceutical. November 27, 2024. Accessed November 27, 2024. https://en.kelun-biotech.com/newsCenter.aspx?mid=18
2. Xu B, Yin Y, Fan Y, et al. Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): results from the phase III OptiTROP-Breast01 study. J Clin Oncol. 2024;42(suppl 16):104. doi:10.1200/JCO.2024.42.16_suppl.104