Tucatinib + T-DXd posts 51% ORR in pretreated HER2+ metastatic breast cancer

Tucatinib is an oral HER2-selective TKI combined here with trastuzumab deruxtecan, a HER2-directed antibody–drug conjugate carrying a topoisomerase I payload, in the single-arm, open-label Phase 2 HER2CLIMB-04 trial (NCT04539938). Patients had unresectable locally advanced/metastatic HER2+ breast cancer after prior HER2 therapy and a taxane, with stable or progressing brain metastases allowed (n=70; median 2 prior metastatic lines); confirmed ORR was 51.4%, median DOR 11.9 mo, median PFS 11.5 mo, and median OS 28.4 mo. The efficacy looks broadly in-family with historical T-DXd monotherapy in later-line HER2+ mBC rather than clearly additive, while toxicity was GI-heavy with diarrhea (80%), nausea (77.1%), and fatigue (72.9%); antidiarrheal prophylaxis reduced diarrhea, but ILD/pneumonitis detail was not available in the abstract.