A phase 1b clinical trial, referred to as “LumOnate”, is investigating a combination of three therapies, for metastatic castration-resistant prostate cancer (mCRPC). The trial combines ¹⁷⁷Lu-PSMA-I&T, a radioligand therapy targeting prostate-specific membrane antigen (PSMA) to deliver radiation and damage cancer cell DNA, with olaparib, a PARP inhibitor that blocks DNA repair, and pembrolizumab, an immune checkpoint inhibitor that enhances T-cell activity against cancer. Related studies provide context for this approach.
The ECLIPSE trial (NCT05204927) showed ¹⁷⁷Lu-PSMA-I&T extends progression-free survival compared to hormonal therapies.
The PRINCE trial (NCT03805594) reported a 56% response rate with ¹⁷⁷Lu-PSMA-617 and pembrolizumab, while the LuPARP trial (NCT03874884) noted a 66% PSA decline with ¹⁷⁷Lu-PSMA-617 and olaparib.

The combination aims to target cancer through direct radiation, DNA repair inhibition, and immune activation, potentially addressing tumor resistance.

Clinical trial.