Tarlatamab in relapsed small-cell lung cancer: a DLL3-targeted bispecific T-cell engager.

Abstract

Relapsed small cell lung cancer (SCLC) is widely considered as a difficult-to-treat disease with an adverse prognosis and scarce therapeutic options, especially in the case of platinum-resistance. Tarlatamab (IMDELLTRA™), a first-in-class, Delta-like ligand-3 (DLL3)-targeted bispecific T-cell engager (BiTE), works by creating a molecular bridge between DLL3 on tumor cells and CD3 on T-cells, leading to T-cell activation and Τ-cell-mediated tumor cell lysis. Tarlatamab demonstrated promising efficacy in early-phase trials at the cost of immune-mediated toxicities like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS emerge primarily during the first two cycles of treatment, have low to moderate severity and are generally manageable with general supportive measures and specialized immunosuppressive treatment including corticosteroids and monoclonal antibodies like tocilizumab. Tarlatamab appears to be a promising choice for relapsed SCLC, based on the results of the Phase III DeLLphi-304 trial, which demonstrated a clinically and statistically meaningful improvement in overall survival (OS) with its use compared to approved second-line chemotherapy (ChT) options. Having been recently granted FDA approval for use in patients with SCLC who progressed on or after platinum-based ChT, tarlatamab is currently being evaluated in multiple settings of SCLC, including first-line and maintenance treatment. Small cell lung cancer is a very aggressive type of lung cancer. The management of patients whose cancer comes back after the initial treatment is considered as a difficult-to-solve riddle with no significant breakthrough for many years and a few therapeutic options based on chemotherapy. Tarlatamab (IMDELLTRA™) is a new, targeted drug that establishes a connection between the cancer cells and a subgroup of the patient’s immune cells, enabling the latter to localize and destroy the tumor. This drug has been shown to be more effective than standard chemotherapy for patients whose cancer has come back after platinum-based treatment. Specifically, a major study (DeLLphi-304) found that tarlatamab helped patients live longer and kept the disease under control for a longer period compared to chemotherapy. While tarlatamab can cause side effects related to the immune system or to the nervous system due to its mechanism of action, these are usually mild and happen early in the treatment. Based on this study, tarlatamab has recently been approved by the FDA for the treatment of relapsed small cell lung cancer and is under ongoing assessment for other indications like newly diagnosed small cell lung cancer.