HER3-Targeted Therapy Shows Promise against NSCLC Brain Metastases in Early Trial
Boston, MA – November 17, 2025 - A new targeted antibody-drug conjugate (ADC), patritumab deruxtecan – known as HER3-DXd – is demonstrating encouraging activity against non-small cell lung cancer (NSCLC) that has spread to the brain, even in patients who have previously undergone local treatments like radiation. Preliminary results from the ongoing TUXEDO-3 study suggest the therapy coudl offer a vital new systemic treatment option for a patient population with limited alternatives.
Brain metastases are a frequent and devastating complication of NSCLC, significantly impacting quality of life and survival. Current systemic therapies often struggle to effectively cross the blood-brain barrier, leaving a critical unmet need for treatments specifically designed to target cancer cells within the brain. HER3-DXd uniquely combines an antibody that recognizes the HER3 protein – frequently overexpressed in NSCLC, particularly in brain metastases – with the potent chemotherapy agent deruxtecan, delivering a targeted cytotoxic effect.
The TUXEDO-3 study, a multicenter, single-arm phase II trial utilizing a Simon’s two-stage design, is evaluating HER3-DXd across three distinct cohorts: patients with metastatic breast cancer and active brain metastases, those with advanced NSCLC and active brain metastases, and individuals with active brain metastases and leptomeningeal disease (LMD) caused by solid tumors.While the study is still in progress, initial data indicate HER3-DXd’s potential to benefit NSCLC patients even after prior brain treatments. Confirmation through larger-scale studies is anticipated to further validate these findings.
