OMNIRAY: a Phase 1 Clinical Trial for LY4257496 for mCRPC

The OMNIRAY trial will be investigating LY4257496, a novel radioligand therapy and it is set to begin in August 2025.

This phase 1a/1b, multicenter, open-label study aims to establish the safety, tolerability and dosimetry of LY4257496 in adult patients bearing advanced solid tumors that express the gastrin-releasing peptide receptor (GRPR). The trial proposes a two-part format: phase 1a explores escalating doses to find the optimal balance between safety and effectiveness, while phase 1b expands the investigation to assess tumor response when administered either alone or alongside standard cancer treatments. Patients diagnosed with GRPR-positive advanced or metastatic tumors, specifically in breast, colorectal, endometrial and castration-resistant prostate cancers,will be enrolled. Participation may extend up to 36 weeks or until disease progression, and the study is expected to enroll around 421 subjects across sites in the United States and Canada.

Note: Prior exposure to Pluvicto is allowed for prostate cancer patients.

Radioligand therapy, the platform for LY4257496, marries a targeting molecule (ligand) with a radioactive isotope, creating a compound that can deliver radiation with precision to cancerous cells while sparing healthy tissue. This approach offers a systemic and targeted attack on tumor cells by homing in on specific biomarkers such as GRPR.

Despite the strong precedent in the field, the actual radioactive element used in LY4257496 remains unreported in the current clinical trial documentation. In the broader radioligand landscape, beta emitters like Lu-177 are widely favored due to their balance of efficacy and tissue penetration, while alpha emitters such as Ac-225—though more potent—are still under exploratory investigation for their localized cytotoxic advantage.

Clinical trial.