TITLE:
Tarlatamab in Small-Cell Lung Cancer: Clinical Validation of DLL3 as a Therapeutic Target
AUTHORS:
Gustavo Alberto Gutiérrez-Barros, María Victoria Morales-Morales, Carlos Andrés Morales Padilla, Sofía Margarita Marzan Reyes, Juan Felipe Díaz Pérez, Luis Enrique Velez Cantor, Karen Alejandra Montes Valencia, Edwin Javier Delgado Caliz, Sergio Andrés Vides Ricaurte, Isabella Pizarro Castillo
KEYWORDS:
Small-Cell Lung Cancer, Tarlatamab, Dll3, Bispecific T-Cell Engager, Immunotherapy
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.7,
July
15,
2026
ABSTRACT: Small-cell lung cancer (SCLC) remains a highly lethal malignancy, characterized by rapid proliferation, early dissemination, transcriptional plasticity, and frequent relapse after an initial response to systemic therapy. The incorporation of PD-L1 inhibitors into platinum-etoposide chemotherapy has modified the first-line standard for extensive-stage disease, although the absolute survival benefit remains limited and subsequent options continue to show restricted efficacy. Delta-like ligand 3 has emerged as a therapeutic target of particular interest because of its prevalent expression in small-cell lung cancer, its association with the neuroendocrine tumor program, and its limited expression in accessible normal tissues. Tarlatamab is a bispecific T-cell engager directed against DLL3 and CD3, designed to induce redirected T-cell cytotoxicity against DLL3-positive tumor cells, independently of conventional antigen presentation. The available clinical evidence in adults with extensive-stage SCLC progressing during or after platinum-based chemotherapy shows clinically relevant objective responses, prolonged duration of response, and survival benefit compared with investigator-selected standard chemotherapy. These findings position tarlatamab as the first anti-DLL3 strategy with robust clinical validation in this therapeutic setting, without implying automatic extrapolation to earlier lines of therapy, limited-stage disease, or populations not adequately represented in pivotal studies. Its safety profile is dominated by cytokine release syndrome and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome, events that are predominantly early and manageable under protocolized monitoring. Overall, tarlatamab represents a substantial modification of the treatment landscape for post-platinum extensive-stage SCLC and a platform with potential expansion toward earlier lines and combination strategies, currently under investigation.