First Documented Response to Tarlatamab in a Patient With Transformed SCLC Without Actionable Gene Alteration: Case Report

Tarlatamab, a DLL3-targeting bispecific T-cell engager, has exhibited substantial survival benefits in relapsed and refractory extensive-stage SCLC. Its efficacy in transformed SCLC, however, particularly in patients without actionable genetic alterations (AGA), remains largely unknown. Histologic transformation of lung adenocarcinoma without AGAs to SCLC is rare, carrying a poor prognosis because of limited treatment options beyond platinum-based chemotherapy. Here, we report the case of a patient initially diagnosed with stage IV lung adenocarcinoma lacking AGAs, who progressed on multiple lines of systemic therapy and subsequently developed histologic transformation to SCLC. She was treated with tarlatamab, achieving 4 months of treatment response with symptomatic relief and improved performance status. This case represents the first documented evidence of the clinical benefit of tarlatamab in transformed SCLC and highlights its therapeutic potential in this challenging setting.