Datopotamab Deruxtecan, an Emerging ADC

Datopotamab deruxtecan (dato-DXd) is an investigational TROP2-directed ADC currently being investigated versus chemotherapy in the 1L phase 3 TROPION-Breast02 trial (N=600) of locally recurrent, inoperable, or metastatic TNBC in immunotherapy-ineligible patients. Completion is expected in December 2025.

In the phase 3 TROPION-Breast01 trial (N=732) of heavily treated patients, dato-DXd met the co-primary endpoint for blinded independent central review (BICR)-determined PFS benefit over investigator’s choice chemotherapy in HR+/HER2-low or -negative mBC. Notably, after a small initial drop the curves separated in favor of dato-DXd and benefit increased over time (6 mo, 55.2% vs 36.9%; 12 mo, 21.7% vs 9.9%). OS data are immature but show a trend favoring dato-DXd. Common AEs with dato-DXd (6 mg/kg IV Q3W) included nausea (51%) and stomatitis (50%); grade 3+ AEs were less common vs chemotherapy (21% vs 45%) and led to fewer dose interruptions (12% vs 25%). Only 2 patients (2/360) experienced interstitial lung disease (ILD). An FDA decision on regulatory approval is expected in the first quarter of 2025.