According to results from a phase 3 study, Sacituzumab tirumotecan demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) compared with chemotherapy, with a manageable safety profile, among heavily pretreated patients with advanced triple-negative breast cancer.

These data will be presented by Yin Fan, MD, Hunan Cancer Hospital, Changsha, China, at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Sacituzumab tirumotecan is TROP2 antibody drug conjugate with a novel linked to the conjugate payload which is a belotecan-derivative topoisomerase I inhibitor. This novel linker releases the membrane permeable payload to enable the “bystander effect.” TROP2 is highly expressed among patients with triple-negative breast cancer and is associated with worse survival.

This randomized, phase 3 trial enrolled 263 patients with locally recurrent or metastatic triple-negative breast cancer who had received ≥2 prior therapies, including at least 1 in the metastatic setting. Patients were randomized on a 1-to-1 basis to receive either sacituzumab tirumotecan (n = 130) or physician’s choice of chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine; n = 133). Of all patients, 26% had previously received a PD-1/PD-L1 inhibitor and 48% had previously received ≥3 lines of chemotherapy for advanced disease. The primary end point of this study was PFS.

At the interim analysis with a data cutoff on June 21, 2023, the primary end point of PFS was met, with a 69% reduction in risk of progression or death with sacituzumab tirumotecan (hazard ratio [HR]: 0.31; 95% confidence interval [CI], 0.22 to 0.45; P < .00001). The median PFS as assessed by blinded independent central review was 5.7 months in the sacituzumab tirumotecan arm vs 2.3 months in the chemotherapy arm. The 6-month PFS was 43.4% vs 11.1%, respectively. At the first planned interim analysis for OS with a median follow-up of 10.4 months (data cutoff on November 30,2023), the OS was statistically significant with sacituzumab tirumotecan (HR: 0.53; 95% CI, 0.36 to 0.78; P = .0005). The median OS was not reached in the sacituzumab tirumotecan arm vs 9.4 months in the chemotherapy arm. The objective response rates were 43.8% and 12.8%, respectively.

The most common grade ≥3 treatment-related adverse events were neutrophil count decreased (32.3% in the sacituzumab tirumotecan arm vs 47.0% in the chemotherapy arm), anemia (27.2% vs 6.1%), and white blood cell count decreased (25.4% vs 36.4%).

Source:

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. Presented at the ASCO Annual Meeting. May 31 – June 4, 2024; Chicago, IL. Abstract #104