Phase 2 Trial: DLL3 PET Reveals Tumor Heterogeneity in Neuroendocrine Prostate Cancer

New findings suggest that an experimental PET imaging technique targeting DLL3 could help identify neuroendocrine prostate cancer (NEPC) lesions and reveal important differences between metastases within the same patient.

Neuroendocrine prostate cancer is an aggressive form of the disease that can emerge following prolonged treatment with androgen receptor-targeted therapies. These tumors frequently show reduced PSMA expression, making conventional PSMA PET less reliable for detecting and characterizing the disease.

DLL3 is a protein frequently expressed on neuroendocrine cancer cells and is being investigated as a potential target for both imaging and treatment.

The prospective phase 2 study evaluated 89Zr-DFO-SC16.56, an experimental PET tracer designed to detect DLL3 expression, in 23 patients with confirmed or suspected neuroendocrine differentiation.

DLL3 PET identified at least one positive lesion in 17 of 23 patients (74%), with more than 700 lesions analyzed across the study population.

One of the most important findings concerned tumor heterogeneity. Among the 17 patients with positive scans, 11 (65%) had both DLL3-positive and DLL3-negative lesions. This suggests that different metastases within the same patient may have substantially different biological characteristics, potentially complicating treatment with therapies targeting a single protein.

The researchers also compared DLL3 PET with other imaging techniques. Among 11 patients who underwent FDG PET, the two imaging methods produced discordant findings in seven cases (64%), suggesting that they may reveal different aspects of tumor biology.

Importantly, DLL3 PET findings agreed with DLL3 immunohistochemistry results from tumor tissue in 17 of 19 evaluable patients (89%), providing preliminary support for the tracer’s ability to identify DLL3 expression throughout the body.

These findings could have implications beyond diagnosis. DLL3 is also being investigated as a therapeutic target, including in a separate 1hase 1 study evaluating the experimental radioligand 177Lu-DTPA-SC16.56. While the zirconium-89-labeled tracer is designed to visualize DLL3-positive lesions, the lutetium-177-labeled compound aims to deliver therapeutic radiation to tumors expressing the same target.

Source.

Clinical trial.