Telix reports positive safety and dosimetry results from Part 1 of the Phase 3 ProstACT Global trial evaluating TLX591-Tx, a PSMA-targeted lutetium-177 radiopharmaceutical therapy, in patients with metastatic castration-resistant prostate cancer.
Written By: Nikita Jha BPharm
Reviewed By: Pharmacally Editorial Team
Telix Pharmaceuticals has reported positive results from Part 1 of the Phase 3 ProstACT Global study (NCT06520345) evaluating TLX591-Tx (lutetium-177 rosopatamab tetraxetan) in patients with prostate-specific membrane antigen (PSMA) positive metastatic castration-resistant prostate cancer (mCRPC).
TLX591-Tx is an investigational PSMA-targeted radiopharmaceutical therapy rather than a conventional drug alone. The treatment combines a PSMA-binding monoclonal antibody with the radioactive isotope lutetium-177, enabling targeted radiation delivery directly to prostate cancer cells that express PSMA.
After the antibody binds to tumor cells, the attached lutetium-177 emits radiation that damages cancer cells while limiting exposure to surrounding healthy tissue. Unlike small-molecule PSMA radioligand therapies that are mainly cleared through the kidneys, this antibody-based therapy is primarily processed through the liver, which may reduce kidney toxicity. Its larger molecular structure also results in lower uptake in salivary glands, potentially lowering the risk of dry mouth and other gland-related side effects commonly associated with existing PSMA-targeted radiotherapies.
The safety, biodistribution, and dosimetry lead-in phase met its primary objectives, demonstrating an acceptable safety and tolerability profile with no new safety signals.
The lead-in phase enrolled 36 patients with mCRPC previously treated with one androgen receptor pathway inhibitor. Participants received two doses of TLX591-Tx administered 14 days apart in combination with standard therapies including enzalutamide, abiraterone, or docetaxel. All patients completed both planned doses.
Most treatment-emergent non-hematologic adverse events were Grade 1 or 2, with fatigue, nausea, and dry mouth reported most frequently. Hematologic toxicities, including thrombocytopenia and neutropenia, were observed but were transient and manageable, with similar recovery patterns across treatment cohorts.
Dosimetry analyses showed radiation exposure to key organs remained well below established safety limits, with limited uptake in the kidneys and salivary glands. Tumor lesion uptake was consistent across cohorts, and pharmacokinetic analyses indicated sustained radiotracer activity up to 15 days after dosing. No drug-drug interactions affecting TLX591-Tx distribution or clearance were identified when combined with standard therapies.
David N. Cade, Group Chief Medical Officer at Telix, said patients with advanced prostate cancer continue to need better treatment options. He noted that the data support the potential for TLX591-Tx, when combined with standard therapies, to become a future first-line treatment and added that the company plans to engage with the U.S. Food and Drug Administration while continuing enrollment in the Phase 3 expansion stage.
Neeraj Agarwal, ProstACT Global Principal Investigator and Steering Committee member, said the results support combining TLX591-Tx with current standard treatments for mCRPC, including enzalutamide, abiraterone, or docetaxel. He noted that hematologic side effects were consistent with expectations for this therapy class and resolved quickly, while the dosimetry profile and mostly low-grade non-hematologic events indicate good overall tolerability.
Based on these findings, Telix has advanced the trial into Part 2, a global randomized expansion comparing TLX591-Tx plus standard of care versus standard therapy alone. The expansion phase is expected to enroll approximately 490 patients. The company also plans to submit Part 1 data to the U.S. Food and Drug Administration to support an amendment allowing the study to proceed in the United States.
References
ProstACT Global Phase 3 Study (Part 1) Achieves Primary Objectives, 10 March 2026, https://telixpharma.com/news-views/prostact-global-phase-3-study-part-1-achieves-primary-objectives/
The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global), ClinicalTrials.gov ID NCT06520345, https://clinicaltrials.gov/study/NCT06520345
About the Writer
Nikita Jha is a pharmacy graduate with a strong interest in new therapies and healthcare innovations. She is enthusiastic about exploring scientific developments and keeping up with emerging updates in pharmaceutical research. Her work focuses on learning, analyzing, and communicating developments in the healthcare and life sciences space.