ABBV-969 (PSMA/STEAP1 dual-targeting Top1i ADC) drives 45% ORR and 67% PSA50 in heavily pretreated mCRPC

ABBV-969 is a first-in-class dual-targeting antibody–drug conjugate (ADC) against PSMA and STEAP1 delivering a topoisomerase-1 inhibitor payload, evaluated as Q3W monotherapy in the Phase 1 FIH dose-escalation study (NCT06318273) in heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) (n=49; median 5 prior lines; 100% prior ARPI, 84% docetaxel, 39% cabazitaxel, 47% prior Lu-PSMA-617). At doses ≥3mg/kg, confirmed PSA50 and PSA90 rates were 67% and 28%, and among RECIST-evaluable patients (n=29) investigator-assessed confirmed ORR was 45% (radiographic PFS pending); for context, post-ARPI/post-taxane PSMA-targeted radioligand Lu-PSMA-617 improved median OS to 15.3 vs 11.3 months (HR 0.62) and is a key SOC option, but ADC cross-trial comparisons are limited without rPFS/OS. Safety was dominated by cytopenias—Grade ≥3 TEAEs in 63% (notably Grade 3 anemia in 24/49), DLTs in 6% (anemia at ≥8mg/kg), TEAE-driven discontinuation in 6%, and 1 treatment-related death from pneumonitis (2%).