ABBV-706 (SEZ6-targeted Top1i ADC) posts 52% ORR in relapsed/refractory SCLC, RP2D set at 1.8mg/kg Q3W

ABBV-706 is a SEZ6-directed antibody–drug conjugate delivering a topoisomerase-1 inhibitor (Top1i) payload, evaluated in an open-label Phase 1 dose-escalation/optimization/expansion trial across advanced solid tumors (N=288; monotherapy N=240), including a relapsed/refractory (R/R) SCLC monotherapy cohort (n=124; NCT05599984). In R/R SCLC, investigator-assessed ORR was 52% (65/124); in the Part 2 dose optimization/expansion cohorts, ORR was similar at 1.8mg/kg vs 2.5mg/kg (56% [23/41] vs 59% [23/39]), while exploratory durability and survival numerically favored 1.8mg/kg with median OS 12.4 months—above typical single-agent topotecan outcomes in relapsed SCLC (ORR generally ~5–20% with short median OS in refractory disease) and higher than the Phase 2 lurbinectedin benchmark (ORR 35.2%, median OS 9.3 months) used clinically post-platinum, though cross-trial comparisons are fragile. Safety was materially myelosuppressive: in the monotherapy population, any-grade TRAEs included anemia (61%) and fatigue (38%), with Grade ≥3 TRAEs in 61% overall and dose-dependent (39% at 1.8mg/kg vs 70% at 2.5mg/kg); in R/R SCLC, any-grade TRAEs were 93% and Grade ≥3 TRAEs 61%, supporting 1.8mg/kg Q3W as the RP2D.