A promising new study is underway to explore the potential of combining FPI-2265 (225Ac-PSMA-I&T), a targeted alpha therapy, with olaparib, a PARP inhibitor, in treating metastatic castration-resistant prostate cancer (mCRPC). This open-label, multicenter Phase 2 trial aims to assess the efficacy, safety, and tolerability of this combination in patients with mCRPC, a particularly aggressive form of prostate cancer that no longer responds to standard hormone therapies.

NOTE: in this study olaparib is used as adjuvant and enrolment does not require any HRR mutation (like BRCA, ATM,…)

The study is structured in two parts to address different patient groups. Part A focuses on individuals who have previously received lutetium-177 (177Lu)-based PSMA-targeted radioligand therapy, such as 177Lu-vipivotide tetraxetan (Pluvicto). Part B, on the other hand, enrolls patients who have not been treated with these therapies. This division allows researchers to evaluate how prior exposure to similar treatments might influence outcomes.

Patients with PSMA-positive mCRPC—confirmed through imaging—are assigned alternately to one of two arms until the first stage of enrollment is complete:
Arm 1: Participants receive up to six doses of FPI-2265 at a specified dose (Dose A) every six weeks, alongside olaparib taken twice daily on days 1 to 14 of each cycle.

Arm 2: Participants receive up to nine doses of FPI-2265 at a different dose (Dose B) every four weeks, with olaparib administered on the same twice-daily schedule for days 1 to 14.

Throughout the study, participants are closely monitored for signs of efficacy, such as tumor response, as well as for disease progression and any adverse events. The primary aim is to determine the recommended dose and regimen based on a comprehensive analysis of safety, tolerability, and anti-tumor activity.
This trial represents a significant step toward addressing the unmet needs of patients with mCRPC, a condition with limited treatment options and poor prognosis. By combining the precision of PSMA-targeted alpha therapy with the DNA repair-targeting mechanism of olaparib, researchers hope to enhance anti-tumor effects while maintaining an acceptable safety profile.

Clinical trial.