VECTRA-01 Phase 3 Trial Tests Alpha-Emitting AZD2265 in PSMA-Positive mCRPC

A pivotal Phase 3 trial called VECTRA-01has launched to evaluate AZD2265 (²²⁵Ac-PSMA-I&T), an alpha-emitting radioligand therapy targeting PSMA-positive metastatic castration-resistant prostate cancer. The study began in May 2026, enrolling approximately 670 participants across 90 global sites, with recruitment currently active at select locations. The trial’s primary objective is to demonstrate superiority over standard of care through dual endpoints: radiographic progression-free survival and overall survival.

AZD2265 delivers targeted alpha radiation using actinium-225, which deposits higher energy over shorter distances compared to beta-emitting PSMA therapies like ¹⁷⁷Lu-PSMA-617 (Pluvicto), potentially offering different therapeutic advantages. Participants must have PSMA-positive mCRPC that progressed after receiving at least two androgen receptor pathway inhibitors, one taxane-based chemotherapy, and critically, at least two cycles of PSMA-directed beta-emitting radioconjugate. This positioning addresses patients who have failed beta-emitter therapy, a population with limited treatment options and suboptimal outcomes.

The randomized design allocates patients to AZD2265 or investigator’s choice of standard of care: cabazitaxel, ARPI switch, or radium-223. Treatment continues until disease progression or unacceptable toxicity, with all participants followed for survival until study completion. Exclusions include prior alpha-emitting radioconjugate therapy (except radium-223), progression on beta-emitter before Cycle 3, and persistent Grade 2+ toxicities from previous therapy.

The global trial design and stringent eligibility criteria reflect the complexity of conducting Phase 3 oncology research in heavily pre-treated mCRPC. Results will clarify whether alpha-emitting PSMA-targeted radioconjugates belong in the treatment algorithm and could establish AZD2265 as the first alpha-emitter approved for this indication, potentially reshaping treatment sequencing for PSMA-positive advanced prostate cancer.

Clinical trial.