Multinational phase 1b-trial of safety and efficacy of tarlatamab in patients with neuroendocrine prostate cancer

Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer with poor prognosis and limited treatment options. As NEPC aberrantly expresses delta-like ligand 3 (DLL3), the multinational phase 1b trial DeLLpro-300 study evaluated tarlatamab,a bispecific bispecific T-cell engage that direct cytotoxic T cells to DLL3-positive cells, in patients with metastatic NEPC. The study enrolled 40 patients (DLL3-positive tumors, n=18; DLL3-negative tumors, n-14; DLL3 unknown tumors, n=8). The most common treatment-related adverse events were cytokine release syndrome (no grade 4 or 5; occurring only in cycle 1, and transient in duration), dysgeusia, and decreased appetite. ORR was 10.5% with median duration of response 7.3 months in the overall cohort. Patients with DLL-positive tumors (versus other patients) achieved higher ORR (22% versus 0) and radiographic progression-free survival at 6 months (27.7% versus 0). The authors conclude that DeLLpro-300 provides preliminary evidence for the safety and antitumor activity of tarlatamab in DLL3-positive NEPC.