Tarlatamab (DLL3×CD3 BiTE) MAIC suggests OS edge vs paclitaxel/CAV in platinum-refractory ES-SCLC

Tarlatamab is a DLL3×CD3 bispecific T-cell engager (BiTE) that redirects cytotoxic T cells to DLL3-expressing SCLC cells; here, an unanchored matching-adjusted indirect comparison (MAIC) used DeLLphi-304 individual patient data (Phase 3; NCT05740566) and reweighted it to published paclitaxel (Owonikoko 2020; NCT02038647; chemotherapy-free interval <180 days) and CAV (GFPC 0501; NCT00418743; CFI <90 days) populations. After MAIC reweighting, tarlatamab improved overall survival vs paclitaxel (HR 0.35, 95% CI 0.23–0.52; p<0.001) and vs CAV (HR 0.48, 95% CI 0.32–0.70; p<0.001); PFS/ORR/DCR also favored tarlatamab vs paclitaxel (p<0.05) but were not significantly different vs CAV (p>0.05). For real-world context, DeLLphi-304’s head-to-head chemo control arm (topotecan/lurbinectedin/amrubicin) reported mOS 8.3 months vs 13.6 months with tarlatamab (trial-level benchmark for 2L ES-SCLC), but this MAIC is still cross-trial and unanchored, so residual confounding is a central limitation.