Safety and Efficacy of Tarlatamab in patients with Neuroendocrine Prostate Cancer: Results from the Phase 1b DeLLpro-300 Study

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 activity of tarlatamab, a bispecific T-cell engager (BiTE®) that directs cytotoxic T cells to DLL3‑positive (DLL3+) cells, was evaluated in the DeLLpro-300 study (NCT04702737). This was a phase 1b, open-label study evaluating tarlatamab monotherapy in patients with metastatic de novo or treatment-emergent NEPC defined by histologic, genomic, or immunohistochemistry (IHC) criteria. Tarlatamab was administered intravenously every 2 weeks at a dose of 100 mg with a 1-mg step dose. The primary objective was safety, and a secondary objective was objective response rate (ORR) per RECIST v.1.1; DLL3 expression was retrospectively assessed by IHC. Forty patients were enrolled (DLL3+ tumors, n=18; DLL3- tumors, n=14; DLL3 unknown tumors, n=8). The most common treatment-related adverse events were cytokine release syndrome (CRS; 82.5%), dysgeusia (42.5%), and decreased appetite (40.0%). CRS was predominantly low grade (grade 1/2/3/4+, 62.5%/15%/5%/0%), occurred exclusively in cycle 1, and was transient in duration (median duration, 3 days). ORR was 10.5% (95% CI, 2.9-24.8); the median duration of response was 7.3 months in the overall cohort. Patients with DLL3+ tumors (vs patients with DLL3-/DLL3 unknown tumors) acheived a higher ORR (22.2% [95% CI, 6.4-47.6] vs 0% [95% CI, 0-15.4]) and radiographic progression-free survival rate at 6 months (27.7% [95% CI, 8.7-50.9] vs 0%). The DeLLpro-300 study provides preliminary evidence for the safety and antitumor activity of tarlatamab in DLL3+ NEPC.