Determinants of long-term response to patritumab deruxtecan in breast cancer patient-derived xenografts.

ABSTRACT: Novel antibody-drug conjugates (ADCs) have shown potent antitumor activity across multiple cancer types. However, the key determinants of therapeutic response remain under investigation. In this study, we aimed to identify potential determinants of long-term response to patritumab deruxtecan (HER3-DXd; MK-1022), a HER3-directed ADC linked to a potent topoisomerase I inhibitor (TOP1i) payload, using a cohort of thirty-one breast cancer (BC) patient-derived xenograft (PDX) models. Fourteen out of 31 (45%) PDXs exhibited a profound and sustained response to HER3-DXd. Basal-like PAM50 intrinsic subtype, limited prior exposure to chemotherapy and intrinsic sensitivity to the TOP1i irinotecan were associated with long-term response. Additionally, HER3-DXd showed sustained activity in BRCA1/BRCA2

SUBMITTER: Odena A 

PROVIDER: S-EPMC12678423 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature