Phase 3 AZD2265 (FPI-2265) Actinium-225 PSMA-targeted alpha radioconjugate vs physician’s-choice SOC in mCRPC

AstraZeneca’s VECTRA-01 is a randomized, multicenter Phase 3 study testing AZD2265 (FPI-2265), a PSMA-binding small-molecule radioconjugate labeled with actinium-225 that delivers high–linear energy transfer alpha radiation to PSMA-expressing tumor sites. Patients have PSMA-positive metastatic castration-resistant prostate cancer progressing despite ongoing androgen deprivation therapy (or prior orchiectomy), and the trial aims to show superiority on radiographic progression-free survival and overall survival versus investigator’s choice standard options. The control arm reflects real-world sequencing: cabazitaxel (a microtubule/tubulin inhibitor chemotherapy), an androgen-receptor pathway inhibitor switch (abiraterone inhibits CYP17 androgen synthesis; enzalutamide/apalutamide/darolutamide/rezvilutamide directly inhibit the androgen receptor), or radium-223 (a bone-seeking alpha emitter for symptomatic bone-predominant disease). The key scientific/commercial angle is whether targeted alpha therapy can outperform established post-ARPI strategies and expand beyond today’s care, which is continued ADT plus sequential ARPIs, taxane chemotherapy, bone-targeted radionuclide therapy in select patients, and PSMA-directed radioligand therapy where available.