ABBV-706 (SEZ6-targeted topo-1 ADC) posts 52% ORR and 11.3-mo OS in R/R SCLC; combo with budigalimab looks feasible

ABBV-706 is a seizure-related 6 homolog (SEZ6)-targeting antibody–drug conjugate delivering a topoisomerase-1 inhibitor payload; this Phase 1 study (NCT05599984) tested ABBV-706 Q3W as monotherapy (N=124; 65% had ≥2 prior lines) or at 1.8mg/kg Q3W plus budigalimab (anti–PD-1) as 2L (n=11). Monotherapy delivered ORR 52% overall (56% at 1.8mg/kg; 82% in the small 2L subset n=17), with median DoR 5.3 months, median PFS 5.4 months, and median OS 11.3 months overall (14.3 months in 2L at 1.8mg/kg), which is numerically above typical 2L lurbinectedin benchmarks (ORR ~35%, mPFS ~3.5 months, mOS ~9.3 months). In the ABBV-706+budi 2L cohort, ORR was 55% with mPFS 8.1 months and median DoR 6.7 months (mOS not yet estimable); grade ≥3 TRAEs were 46% (notably anemia 27%, neutrophils decreased 18%), with 0% discontinuations but frequent interruptions (64%) and reductions (36%) and no pneumonitis reported.