Phase 3 data presented at ASCO 2026 suggest a PSMA-targeted radiopharmaceutical can be safely combined with standard therapies in metastatic castration-resistant prostate cancer.

Data presented in a late-breaking oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting have shown that a prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical can be administered alongside current standard-of-care treatments in patients with metastatic castration-resistant prostate cancer (mCRPC), supporting further evaluation in a randomized Phase 3 study.

The findings come from Part 1 of the ProstACT Global Phase 3 trial evaluating TLX591-Tx (lutetium-177 rosopatamab tetraxetan), an investigational radio antibody-drug conjugate being developed by Telix Pharmaceuticals.

The international study is assessing TLX591-Tx in combination with standard therapies including abiraterone, enzalutamide and docetaxel in patients with PSMA-positive mCRPC who have previously received one androgen receptor pathway inhibitor.

Results presented at ASCO demonstrated an acceptable safety and tolerability profile across all treatment cohorts, with no new safety signals observed. All 36 patients enrolled in the safety phase of the study completed both planned doses of TLX591-Tx.

Most treatment-emergent non-haematologic adverse events were Grade 1 or Grade 2, with fatigue, nausea and dry mouth among the most commonly reported events. Investigators reported that haematologic toxicities, including thrombocytopenia and neutropenia, were transient and generally consistent with those expected for this patient population and therapeutic class.

The study also examined radiation dosimetry and pharmacokinetics. Researchers found radiation exposure to major organs remained below established safety thresholds, while imaging confirmed uptake of the therapy across tumour sites in all treatment cohorts.

Importantly, investigators reported evidence of sustained tumour retention through Day 15 following administration, suggesting prolonged tumour targeting activity. No evidence of drug-drug interactions affecting targeting, distribution or clearance of the therapy was identified.

Pedro Barata, principal investigator of the study, said: “These results support the feasibility of administering TLX591-Tx alongside current standard-of-care therapies for mCRPC, including ARPIs. Imaging demonstrated sustained tumor retention through day 15, while dosimetry analyses showed radiation exposure below established safety thresholds and limited dose to key organs.”

He added: “Overall, the safety, dosimetry, and tumor-targeting findings, together with the high treatment compliance observed in this study, support further evaluation of this approach, in the randomized phase of the trial.”

Metastatic castration-resistant prostate cancer remains one of the most challenging stages of prostate cancer treatment, despite advances in hormonal therapies, chemotherapy and radioligand approaches. Researchers are increasingly investigating how targeted radiopharmaceuticals can be integrated with existing standards of care to improve outcomes while maintaining acceptable safety profiles.

The ProstACT Global study has now progressed into Part 2, a randomized treatment expansion phase that will compare TLX591-Tx plus standard of care against standard treatment alone. Recruitment is underway in jurisdictions where regulatory approvals have been granted.

David Cade, group chief medical officer at Telix, said: “Despite meaningful advances in clinical practice, mCRPC remains a disease where patients urgently need additional first and second-line options.”

He added: “These Part 1 results, presented today at ASCO, build on prior clinical findings and further support our view that TLX591-Tx in combination with contemporary standard of care has the potential to become a new treatment option for this aggressive disease.”

While efficacy outcomes remain to be determined in the randomized expansion phase, the ASCO presentation provides an important early indication that combining PSMA-targeted radiopharmaceutical therapy with established prostate cancer treatments may be feasible, supporting continued development of the approach in advanced disease.