T‐cell engagers in small cell lung cancer

Abstract

The management of small cell lung cancer (SCLC) has been transformed by the advent of effective T‐cell engagers (TCEs), which circumvent the traditionally immunosuppressive tumor microenvironment by directly facilitating T‐cell–mediated cell lysis. Delta‐like ligand 3 (DLL3) has emerged as the predominant target for TCE development in SCLC given its high expression on tumor cells and relatively spared expression on normal tissues. Tarlatamab, a DLL3xCD3 TCE that is now an approved agent for SCLC, has revolutionized outcomes for patients with SCLC, but raises challenges in terms of toxicity management and real‐world implementation. In this review, we discuss the current landscape and future directions of DLL3‐targeting TCE in SCLC, including accumulating real‐world clinical experience, nascent investigation into patient selection and modifiers of response and resistance, and anticipated paradigm shifts as a result of ongoing clinical trials.