T-cell engagers in small-cell lung cancer: current evidence and future directions - a position statement from the ETOP IBCSG Partners Foundation Workshop

T-cell engagers (TCEs) are a novel class of immunotherapeutic molecules that enhance immune responses to cancer by directing T cells to target tumour cells. Tumour-associated antigens have been identified for several solid malignancies, including delta-like ligand 3 (DLL3) for small-cell lung cancer (SCLC). Several DLL3-targeted TCEs are being developed for the treatment of SCLC, including tarlatamab, gocatamig and obrixtamig. Tarlatamab is approved by the United States Food and Drug Administration and represents a new standard of care in patients with pretreated SCLC. As experience with TCEs in SCLC increases, consensuses on optimal clinical settings and patient management are evolving. Rapid identification and effective management of potentially life-threatening immune-related side-effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), are essential for successful treatment with TCEs. Here we briefly review the key studies of TCEs in development for solid tumours before providing a comprehensive discussion on the clinical management of TCE therapy in patients with SCLC. We consider issues related to clinical settings, patient evaluation and management of toxicities, with a particular focus on identification and treatment of CRS and ICANS, drawing on experience from other oncology settings. TCEs represent a transformative treatment option for SCLC, offering new hope for a disease traditionally associated with poor therapeutic outcomes. TCEs also, however, bring new challenges, including the effective management of immune-related side-effects and the logistical demands of treatment. Safe implementation will depend on robust infrastructure, multidisciplinary collaboration, and patient and caregiver education.