Mali Barbi, Medical Oncologist at Northwell Health, shared a post on X:
”Two prospective phase II trials at ESMOBC26 just settled something the field has been debating retrospectively.
- SATEEN (LBA4):saci + trastuzumab after prior T-DXd in HER2+ MBC. ORR 3.7%. One response in 27 patients. Median PFS 2.3 months. Stopped for futility.
- HER3-DXd: ORR 39% in ADC-naive HR+/HER2- disease. Prior TOPO1 ADC exposure wiped that out across every subtype.
Different antibody targets. Same collapse. Because resistance here is payload-driven, not antigen-driven.
SN-38 and DXd are different molecules but the same mechanism. Abelman et al. (Clin Cancer Res 2025) showed acquired TOP1 mutations in 12.9% of patients at ADC progression median duration on the second TOPO1 ADC: 52 days versus 455 on the first.
Post-ADC trial design has to start from the payload up, not the target down.”
