Phase 1b tarlatamab DLL3×CD3 T‑cell engager + ZL‑1310 DLL3 Topo‑I ADC ± durvalumab

Amgen’s open-label Phase 1b study tests whether dual DLL3 targeting can deepen responses in relapsed/recurrent small cell lung cancer: tarlatamab (a DLL3×CD3 bispecific antibody that redirects T cells to DLL3-expressing tumor cells) is combined with ZL‑1310 (a DLL3-targeted antibody–drug conjugate delivering a topoisomerase I inhibitor payload to kill dividing cells), with an optional triplet adding AstraZeneca’s durvalumab (a PD‑L1–blocking monoclonal antibody) to potentially enhance anti-tumor immunity. Part 1 is dose exploration to determine the maximum tolerated combination dose and/or recommended Phase 2 dose for ZL‑1310 with tarlatamab; Part 2 expands at the selected dose; Part 3 evaluates the triplet. Eligible participants include SCLC (including extensive-stage SCLC cohorts) that has progressed or recurred after platinum-based therapy in the second-line or later setting. Commercially, it’s a notable “DLL3-on-DLL3” combination pairing a T-cell engager with a cytotoxic ADC, aiming to improve on today’s care where most patients receive lurbinectedin or topotecan (and, when accessible, DLL3-directed tarlatamab) after platinum + etoposide ± PD‑L1 in first line.