AstraZeneca has begun enrolling VECTRA-01, a Phase 3 randomised controlled study of AZD2265 (also known as FPI-2265), an actinium-225 (²²⁵Ac) alpha-emitting PSMA-I&T radioligand therapy, in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The trial is now recruiting, with a study start recorded as 4 May 2026.

The design targets a population that has run out of established options. Eligible men must already have been treated with at least two cycles of a PSMA-directed beta-emitting radioconjugate — the class that includes ¹⁷⁷Lu-PSMA — alongside prior taxane chemotherapy and a prior androgen-receptor pathway inhibitor (ARPI). PSMA positivity is confirmed by ⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL PET/CT. Prior alpha-emitting radioligand therapy is excluded, though prior radium-223 is permitted.

Two co-primary endpoints, a superiority design

Roughly 670 participants will be randomised to AZD2265 or to investigator’s choice of standard of care — cabazitaxel, an ARPI switch, or radium-223. The study has two co-primary endpoints: radiographic progression-free survival (rPFS) by blinded independent central review per RECIST 1.1 and PCWG3, and overall survival (OS). AstraZeneca states that the intent is to demonstrate superiority of AZD2265 over standard of care on both rPFS and OS.

The trial is built around men who have already progressed through a beta-emitting PSMA radioligand — a question the field has not yet answered in Phase 3.

Secondary endpoints include composite PFS; PSA50 and PSA90 response rates; objective response rate; duration of response; symptomatic skeletal event-free survival; and AZD2265 pharmacokinetics. An Independent Data Monitoring Committee will oversee safety. Treatment continues until progression, unacceptable toxicity, or other discontinuation criteria are met; estimated primary completion is 13 February 2029.

VECTRA-01 is a genuinely global effort. The registry lists research sites across 16 countries: the United States, Canada, Brazil, the United Kingdom, Germany, France, Spain, Austria, China, Japan, South Korea, Taiwan, India, Thailand, Turkey, and Australia. Most are listed as not yet recruiting, with active recruitment so far recorded only in Miami and Omaha.

No efficacy or safety results exist yet — this is a newly opened trial, not a readout. The asset’s distinction is its radioisotope: an alpha-emitter delivering high-energy, short-range radiation, tested specifically after beta-emitter therapy.