Phase 3 ABBV-706 SEZ6-targeted topo-1 ADC vs chemotherapy in R/R SCLC

AbbVie’s randomized, open-label Phase 3 trial tests ABBV-706 against physician’s-choice topotecan, lurbinectedin, or amrubicin in roughly 531 patients with relapsed/refractory SCLC. ABBV-706 is a SEZ6-directed antibody-drug conjugate that internalizes into SEZ6-expressing tumor cells and delivers a topoisomerase 1 inhibitor payload, causing DNA damage and cell death. The pivotal study follows Phase 1 data in 124 R/R SCLC patients showing 52% ORR overall; at the selected 1.8 mg/kg dose, ORR was 56%, median PFS 6.4 months, and median OS 12.4 months, while a small second-line subset (n=17) reached 82% ORR, 6.8-month PFS, and 14.3-month OS. Grade ≥3 treatment-related AEs were 39% at 1.8 mg/kg versus 70% at 2.5 mg/kg, supporting the lower dose for further development. Importantly, current Phase 3 eligibility generally requires prior tarlatamab exposure; tarlatamab (Amgen’s DLL3×CD3 bispecific) is now FDA-approved after platinum, so this study is testing whether SEZ6-targeted ADC therapy can outperform chemotherapy in an increasingly post-tarlatamab treatment setting.