Phase 1 ProTACT: Actinium-225 FL-020 Shows Early Activity in Advanced Prostate Cancer

New results show preliminary antitumor activity for 225Ac-FL-020, an investigational PSMA-targeted alpha radioligand, in patients with metastatic castration-resistant prostate cancer (mCRPC).

The findings come from ProTACT, an ongoing first-in-human phase 1 trial evaluating the safety, dosing, and preliminary efficacy of FL-020 in patients previously treated with androgen receptor pathway inhibitors and taxane chemotherapy, unless chemotherapy was declined. Previous treatment with lutetium-177 PSMA radioligand therapy was permitted.

FL-020 is designed to deliver the alpha-emitting isotope actinium-225 to PSMA-expressing tumor cells while potentially limiting radiation exposure to healthy organs, particularly the salivary glands.

As of May 8, 2026, 27 patients had received treatment at doses up to 7 MBq per cycle, administered every six weeks. Sixteen patients remained on treatment, while ten had discontinued, primarily because of disease progression.

Among 22 patients evaluable for PSA response, nine (40.9%) achieved a PSA reduction of at least 50% (PSA50). At the 6 MBq dose level, five of six evaluable patients (83.3%) achieved PSA50. Three patients across the dose cohorts achieved PSA reductions of at least 80%. Partial radiological responses were observed in two of five RECIST-evaluable patients.

The most frequently reported adverse events were fatigue, nausea, dry mouth, and decreased appetite. Dry mouth was limited to grade 1–2, although one patient discontinued treatment because of grade 2 xerostomia.

Grade 3 or higher treatment-related adverse events occurred in four patients (14.8%), primarily involving lymphocytopenia, anemia, and decreased appetite. No dose-limiting toxicities were observed, and the recommended Phase 2 dose had not yet been established.

Source.

Clinical trial.