NCT07090369

Phase Ib Trial of 177Lu-PSMA-I&T Therapy in Combination With Olaparib and Pembrolizumab in Patients With Metastatic Castration Resistant Prostate Cancer

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Peter MacCallum Cancer Centre, Australia · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase 1b trial is designed to evaluate the safety and tolerability of olaparib in combination with 177Lutetium-Prostate Specific Membrane Antigen (177 Lu-PSMA) and pembrolizumab in patients with metastatic castration resistant prostate cancer (mCRPC).

Detailed description

This phase 1b, multi-centre, single arm, open label study is designed to evaluate the safety and tolerability of olaparib in combination with 177Lu-PSMA with concurrent treatment with pembrolizumab in patients with mCRPC. Patients with mCRPC who have previously progressed an Androgen Receptor Pathway Inhibitor (e.g. enzalutamide, abiraterone, darolutamide/or apalutamide) and have not had prior exposure to anti-PD-1, anti-PD-L1/L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathway, platinums, PARP inhibitors or radionuclide therapy will be eligible for the study. Patients can have had prior exposure to docetaxel in the chemotherapy naïve setting or castrate setting. This is a single arm study divided into two treatment parts. In Part 1, patients will receive olaparib (oral; day 1-22),177Lu-PSMA (IV infusion; day 5), and pembrolizumab (IV infusion; day 1 and 22) for a maximum of six cycles (cycle = 42 days) of treatment. In Part 2, patients will continue to be treated with single agent pembrolizumab (IV infusion; day 1 and 22) for a subsequent 12 cycles (cycle = 42 days) of treatment. Patients will be followed up every six weeks after the last dose of treatment until disease progression by modified RECIST 1.1 and/or PCWG3, start of new anti-prostate cancer therapy, withdrawal of consent, death, or 2 years a er the last patient has commenced treatment, whichever is earlier.

Conditions

• Metastatic Castrate Resistant Prostate Cancer (mCRPC)

Interventions

Type	Name	Description
DRUG	Olaparib (300 mg BID)	oral tablet
DRUG	Pembrolizumab	IV infusion
RADIATION	177Lu-PSMA-I&T	PSMA-I\&T is a small molecule ligand that binds to the extra-cellular domain of the prostatespecific membrane antigen. PSMA-I\&T is a small molecule ligand that binds to the extra-cellular domain of the prostatespecific membrane antigen

Timeline

• Start date: 2025-11-01
• Primary completion: 2028-12-01
• Completion: 2028-12-01
• First posted: 2025-07-29
• Last updated: 2025-07-29

Locations

1 site across 1 country: Australia