Multinational phase 2 trial of patritumab deruxtecan in patients with active brain metastases of breast cancer

Patritumab deruxtecan (HER3-DXd) is a novel antibody-drug conjugate targeting HER3, which is overexpressed in CNS metastases of breast cancer. Cohort 1 of the multinational phase 2 TUXEDO-3 trial evaluated HER3-DXd for patients with breast cancer and brain metastases (BrM) that are newly diagnosed or progressing after local therapy. The threshold for the primaryend point was at least 15% of patients having intracranial response. The trial included 21 female patients (five with luminal breast cancer, nine with HER2-positive breast cancer, ndseven with tripla-negative breast cancer). The median number of previous treatment lines for advanced disease was 4 (IQR 2-4). Median treatment duration was 3.0 months (IQR 0.7-7.7), and median follow-up was 4.9 months (IQR 3.6-8.5). The primary endpoint was met with five of 21 patients having intracranial responses (ORR 23.8%; 95% CI 8.2-47.1). The most common grade 3 or worse treatment-emergent adverse events were neutropenia in 14% of patients, diarrhea in 10%, and asthenia and vomiting in 5% each. No treatment-related deaths were reported. The authos conclude that HER3-DXd showed promising clinical activity in patients with breast cancer and active BrM.