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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2025 Jul 21 [Epub ahead of print]
Rahul Aggarwal, Sylvie Rottey, Alice Bernard-Tessier, Begoña Mellado, Takeo Kosaka, Walter M Stadler, Lisa Horvath, Richard Greil, Bert O'Neil, Bilal A Siddiqui, Thomas Bauernhofer, Mehmet A Bilen, Ferry Eskens, Shahneen Sandhu, Crystal Shaw, Chia Hsin Ju, Benjamin E Decato, Brian Yu, Ana Aparicio
University of California, San Francisco, San Francisco, CA, United States., Ghent University Hospital - 4B11, Ghent, Belgium., Institut Gustave Roussy, villejuif, France., HOSPITAL CLINIC OF BARCELONA, BARCELONA, Spain., Keio University School of Medicine, Tokyo, Japan., University of Chicago, Chicago, IL, United States., Chris O'Brien Lifehouse, Sydney, New South Wales, Australia., Salzburger Landeskliniken, Salzburg, Salzburg, Austria., Indiana University Bloomington, Indianapolis, United States., The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Medical University of Graz, Graz, Austria., Emory University Hospital, Atlanta, GA, United States., Erasmus MC Cancer Institute, Rotterdam, Netherlands., Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Victoria, Australia., Amgen Inc., Thousand Oaks, CA, United States., Amgen (United States), United States., Amgen Inc., South San Francisco, CA, United States.