ESMO 2025 Highlights a New Therapeutic Landscape for SCLC

During the ESMO 2025 Congress we have realized the incredible ongoing developments for patients with small-cell lung cancer (SCLC).

This remains a lethal malignancy despite modest gains with chemo-immunotherapy. Data showcased at the ESMO 2025 signal a true therapeutic inflection point, driven by DLL3-targeted bispecific T-cell engagers and next-generation antibody–drug conjugates (ADCs). In first-line ES-SCLC, the phase Ib DeLLphi-303 trial of tarlatamab plus platinum–etoposide and PD-L1 blockade yielded an ORR of 71%, median PFS 10.3 months and 12-month OS 81%, with predominantly low-grade CRS/ICANS, supporting early DLL3 engagement rather than reserving it for relapse. Complementing this, the phase I DAREON-8 study of the DLL3×CD3 bispecific obrixtamig combined with carboplatin/etoposide–atezolizumab reported a 68% ORR and 89% disease control, with an acceptable safety profile, underscoring the feasibility of chemo-IO plus T-cell redirection in the frontline setting. Concerning ADCs, SEZ6-directed ABBV-706 demonstrated clinically meaningful activity in heavily pretreated SCLC in posters 2777P and 2778P, including rapid ctDNA/CTC clearance, raising the prospect of platinum-sparing, biomarker-integrated strategies. With phase III DeLLphi-304 results confirming an OS benefit for second-line tarlatamab versus chemotherapy, we have previously seen the impressive data as well by targeting B7-H3 with I-Dxd from the Ideate-Lung01 trial (ORR 55%) and new targets are emerging for not only ADCs but also for radioligands for the treatment of SCLC. These data collectively represent a shift from empiric cytotoxic drugs to precisely targeted, immune-integrative treatment paradigms in SCLC.