A novel investigational HER3-targeted antibody-drug conjugate, patritumab deruxtecan, has been evaluated in HER3-expressing advanced breast cancer in the U31402-A-J101 study: results of this phase I/II trial, published on the Journal of Clinical Oncology, show durable antitumor activity and a manageable safety profile across breast cancer subtypes.

HER3 is broadly expressed in breast cancer and high expression is associated with an adverse prognosis, but currently no HER3-directed treatments have been approved for the treatment of any cancer. Patritumab deruxtecan (HER3-DXd) is a novel, first-in-class HER3-directed antibody-drug conjugate that has been evaluated in 182 patients with HER3-expressing advanced breast cancer and disease progression on previous therapies. Authors identified a dose range of HER3-DXd with a favorable risk/benefit profile  (1.6-8.0 mg/kg intravenously), with grade ≥3 treatment-emergent adverse events observed in 71.4% of patients, and 9.9% of patients discontinuing treatment because of treatment-emergent adverse events. Objective responses were observed in cancers with HER3-high and HER3-low membrane expression, with some differences across clinical subtypes: in HR+/HER2- breast cancer objective response rate was of 30.1% and median progression-free survival was 7.4 months, whereas they were of 22.6% and 5.5 months, respectively, in triple-negative breast cancer. «This is the first comprehensive analysis of HER3-DXd in patients with advanced breast cancer and demonstrates clinically meaningful antitumor activity in a heavily pre-treated patient population across a range of HER3 (HER3- high and HER3-low) expression. A manageable and acceptable safety profile was observed in this population with adverse prognostic features. Further evaluation of HER3-DXd as a potential treatment option in advanced breast cancer is ongoing», authors conclude.