Early Phase 1 Trial of GRPR-Targeted Theranostic DOTA-STR-17126

A first-in-human imaging trial of DOTA-STR-17126 just started in Australia. It is an open-label, single-arm early phase 1 study enrolling up to 20 adults with advanced or metastatic prostate or breast cancer who have exhausted standard treatments.

The trial uses a theranostic approach. Participants receive gallium-68 DOTA-STR-17126 for PET imaging to detect tumors expressing the gastrin-releasing peptide receptor (GRPR). Patients with positive GRPR uptake may then receive a low dose of lutetium-177 DOTA-STR-17126 for SPECT imaging and radiation dosimetry.

GRPR is overexpressed in prostate and breast cancer and remains present in some tumors even when PSMA is lost. Approximately 23.5% of metastatic castration-resistant prostate cancers express GRPR despite being PSMA-negative or low, making this a potential target for patients who cannot benefit from PSMA-targeted radioligand therapy.

The study’s primary endpoint is safety and tolerability. Secondary endpoints include PET image quality, biodistribution, pharmacokinetics, and radiation dosimetry. No therapeutic efficacy is expected at the low lutetium-177 dose used; the goal is to establish whether the compound accumulates in tumors and to measure radiation exposure before any future therapeutic trials.

Radioantagonists targeting GRPR show better tumor targeting and clearance than agonists in preclinical studies. Lutetium-177–labeled GRPR ligands have demonstrated tumor responses in animal models without significant toxicity.

If imaging confirms GRPR uptake and acceptable safety, the data could support development of a therapeutic version delivering higher lutetium-177 doses for actual tumor treatment.

Clinical trial.