Investigational Drug
actinium (225Ac) zadavotide guraxetan
TrialFetch AI Analysis
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Overview
Actinium (^225Ac) zadavotide guraxetan—also called FPI-2265, AZD2265, or ^225Ac-PSMA-I&T—is an investigational radioligand therapy being studied in people with PSMA-positive metastatic castration-resistant prostate cancer. Human results are available, but the reported efficacy and safety findings are preliminary and come from small, uncontrolled studies. A randomized phase 3 study is recruiting. (aacrjournals.org)
Mechanism of action
The drug combines a small molecule that binds prostate-specific membrane antigen (PSMA) with actinium-225. This is intended to deliver alpha-particle radiation to PSMA-expressing cancer cells. (aacrjournals.org)
Efficacy
In an interim analysis of the single-arm TATCIST trial, 10 of 20 evaluable patients (50%) had a prostate-specific antigen (PSA) decline of at least 50% (PSA50). An earlier retrospective study of the same ^225Ac-PSMA-I&T compound reported a best PSA50 response in 7 of 14 patients (50%). PSA decline is a measure of activity; these studies do not establish a survival benefit or how the drug compares with other treatments. (aacrjournals.org)
Safety
In TATCIST, treatment-related dry mouth occurred in 18 of 21 patients (86%), fatigue in 10 (48%), and dry eye in 6 (28%). Grade 3 treatment-related anemia occurred in 5 (24%), and decreased platelet count in 3 (14%); no grade 4 or 5 treatment-related events were reported in that analysis. In a separate nine-patient phase 1 study of ^225Ac-PSMA-I&T, dry mouth was also the most frequent adverse event, and two dose-limiting toxicities occurred at the highest tested activity. (aacrjournals.org)
Further reading
- TATCIST preliminary results (AACR conference abstract)
- First clinical results with ^225Ac-PSMA-I&T (Journal of Nuclear Medicine)
- Phase 1 dose-escalation study (Journal of Nuclear Medicine)
- VECTRA-01 phase 3 study record
Last updated: Sep 2026
Active trials using actinium (225Ac) zadavotide guraxetan
Found 2 active trials using this drug:
TrialFetch AI summary: Adults with progressive, PSMA-positive metastatic castration-resistant prostate cancer after one novel androgen receptor pathway inhibitor receive AZD2265, a PSMA-targeted actinium-225 radioligand, plus AZD9574, an oral PARP1 inhibitor. Dose expansion compares the combination with AZD2265 alone and docetaxel.
ClinicalTrials.gov ID: NCT07590934
TrialFetch AI summary: This trial enrolls adults with progressive, PSMA PET-positive metastatic castration-resistant prostate cancer previously treated with a PSMA-directed beta-emitting radioconjugate, a taxane, and an androgen receptor pathway inhibitor. Patients receive AZD2265, an investigational PSMA-targeted actinium-225 radioligand that delivers alpha radiation, or investigator’s choice of cabazitaxel, an androgen receptor pathway inhibitor switch, or radium-223.
ClinicalTrials.gov ID: NCT07611110
