Obrixtamig (BI 764532) + Topotecan Doubles Typical Second-Line Response in Platinum-Relapsed SCLC

Obrixtamig is an IgG-like bispecific T-cell engager that binds DLL3 on tumor cells and CD3 on T cells, while topotecan is the long-standing topoisomerase-I standard for relapsed small-cell lung cancer (SCLC). In the phase Ib DAREON™-9 trial (NCT05990738), 22 patients with extensive-stage SCLC progressing after platinum ± immunotherapy received IV obrixtamig (dose-escalation) plus day-1-to-5 topotecan. ConfirmedORR was 40% in all treated patients and 69% (9/13) in those evaluable, with disease control in 92%. Median duration of response and PFS were not yet reached (cut-off January 2025). Historical IV topotecan monotherapy yields ~17% ORR and 3.5 mo median PFSin this setting, underscoring the combination’s roughly two-fold bump in activity. Safety was dominated by expected grade 3–4 hematologic toxicities from topotecan; cytokine-release syndrome was mostly grade 1–2 with no dose-limiting toxicities or treatment-related deaths.