A Phase 2 trial is investigating the use of tarlatamab, an immunotherapy designed as a bispecific T-cell engager, in patients with neuroendocrine prostate cancer (NEPC), a particularly aggressive form of prostate cancer with limited treatment options. Tarlatamab targets delta-like ligand 3 (DLL3), a protein highly expressed on NEPC tumor cells but absent in most other prostate cancers, enabling it to recruit and activate T cells to selectively attack cancer cells expressing DLL3.

This Phase 2 open-label study focuses on evaluating the safety and preliminary efficacy of tarlatamab in adults with metastatic de novo or treatment-emergent NEPC who have often undergone multiple prior treatments. The trial measures outcomes such as treatment tolerability, side effects—including the manageable cytokine release syndrome commonly associated with T-cell engagers—and objective tumor responses. Early results show that while side effects like low-grade cytokine release syndrome are frequent, they are generally manageable and reversible without requiring discontinuation of treatment.
Among patients with DLL3-positive tumors, preliminary evidence indicates a higher objective response rate and improvements in progression-free survival.

Tarlatamab recently received accelerated approval for a similar indication in extensive-stage small-cell lung cancer, reinforcing the promise of DLL3-targeted therapies in neuroendocrine tumors. By leveraging the specificity of DLL3 expression, tarlatamab offers a targeted immunotherapeutic approach distinct from standard treatments for prostate adenocarcinoma.

Clinical trial.