Investigational Drug
Ac-225 rosopatamab tetraxetan
TrialFetch AI Analysis
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Overview
Ac-225 rosopatamab tetraxetan (also called ²²⁵Ac-J591 or CONV01-α) is an investigational radiopharmaceutical being studied for metastatic castration-resistant prostate cancer (mCRPC). Human results are available from early-phase trials, but they do not yet establish a survival benefit. (ascopubs.org)
Mechanism of action
The drug combines J591, a monoclonal antibody that binds prostate-specific membrane antigen (PSMA) on prostate cancer cells, with actinium-225, which emits cell-damaging alpha radiation. (pubmed.ncbi.nlm.nih.gov)
Efficacy
In a published phase 1 single-dose study of 32 patients, 46.9% had a prostate-specific antigen (PSA) decline of at least 50% at some point; 34.4% had a confirmed decline of that size. A later phase 1 study reported a best PSA decline greater than 50% in 60% of patients receiving two fractionated doses, versus 28% in its multiple-cycle cohort. These PSA measures are preliminary indicators of activity, not proof of improved survival. (pubmed.ncbi.nlm.nih.gov)
In a 2026 conference abstract from the phase 2 CONVERGE-01 trial, 5 of 11 PSA-evaluable patients (45.4%) at the selected dose had a PSA decline of at least 50%. All had previously received lutetium-177–PSMA therapy. The results were interim and based on a small group. (ascopubs.org)
Safety
Low blood-cell counts are an important risk. In the fractionated-dose/multiple-cycle phase 1 study, thrombocytopenia occurred in 93% of patients (32% grade 3 or higher), neutropenia in 65% (13% grade 3 or higher), and anemia in 63% (20% grade 3 or higher). Dry mouth occurred in 62%, predominantly at low grade. Investigators did not recommend the multiple-cycle regimen for further development because of dose-limiting toxicities. In the smaller CONVERGE-01 interim analysis, the selected-dose group had no grade 3 or higher thrombocytopenia and dry mouth was grade 1 or 2; longer follow-up is needed. (pubmed.ncbi.nlm.nih.gov)
Further reading
- Published first-in-human phase 1 study
- Published fractionated-dose and multiple-cycle phase 1 study
- 2026 CONVERGE-01 conference abstract
Last updated: Sep 2026
Active trials using Ac-225 rosopatamab tetraxetan
Found 3 active trials using this drug:
TrialFetch AI summary: Patients have progressive, PSMA PET-positive metastatic castration-resistant prostate cancer after androgen deprivation therapy and an androgen receptor signaling inhibitor; one treatment cohort excludes prior CRPC chemotherapy or PSMA-targeted therapy, while another requires prior lutetium-177–PSMA therapy. After indium-111–rosopatamab tetraxetan imaging, eligible patients receive fractionated actinium-225–rosopatamab tetraxetan, an investigational PSMA-targeting radioantibody that delivers alpha radiation.
ClinicalTrials.gov ID: NCT06549465
TrialFetch AI summary: Men with progressive metastatic castration-resistant prostate cancer, ECOG 0–1, and prior androgen receptor–directed therapy receive pembrolizumab plus an androgen receptor pathway inhibitor, with or without a single dose of ²²⁵Ac-J591. This investigational agent targets PSMA to deliver actinium-225 alpha radiation to tumor cells; prior chemotherapy for castration-resistant disease, checkpoint inhibitors, and investigational PSMA-targeted therapy are excluded.
ClinicalTrials.gov ID: NCT04946370
TrialFetch AI summary: Men with progressive metastatic castration-resistant prostate cancer after androgen receptor pathway therapy, who have received, declined, or are ineligible for taxane chemotherapy, receive two cycles of combined PSMA-targeted radiotherapy. The regimen pairs the alpha-emitting antibody ²²⁵Ac-J591 with a beta-emitting ¹⁷⁷Lu-PSMA small molecule (PSMA-I&T or PSMA-617), in cohorts with and without prior ¹⁷⁷Lu-PSMA exposure.
ClinicalTrials.gov ID: NCT04886986
