Safety and Efficacy of Tarlatamab in patients with Neuroendocrine Prostate Cancer: Results from the Phase 1b DeLLpro-300 Study
Mené sur 40 patients atteints d'un cancer neuroendocrine de la prostate, cet essai de phase IB évalue la toxicité et l'efficacité, du point de vue du taux de réponse objective, du tarlatamab
Purpose: 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).
Patients and methods: 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.
Results: 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%).
Conclusions: The DeLLpro-300 study provides preliminary evidence for the safety and antitumor activity of tarlatamab in DLL3+ NEPC.
Clinical Cancer Research , résumé, 2025