Lutetium-177 rosopatamab tetraxetan

TLX591 (INN lutetium Lu 177 rosopatamab tetraxetan; also referred to as TLX591-Tx) is Telix Pharmaceuticals' lead PSMA-targeted radio-antibody-drug conjugate for metastatic castration-resistant prostate cancer (mCRPC). Unlike small-molecule PSMA ligands (e.g. PSMA-617, PSMA-I&T), TLX591 uses a full-length PSMA-targeting monoclonal antibody, given as two 76 mCi intravenous infusions 14 days apart; its hepatic (rather than renal) clearance means long-term follow-up has not shown significant acute or delayed nephrotoxicity.

By the ProstACT SELECT trial (NCT04786847), 242 patients had been treated with TLX591 across eight phase 1/2 studies; SELECT itself reported a median radiographic progression-free survival of 8.8 months in 23 evaluable mCRPC patients, and an earlier single-arm phase 2 study reported 42.3-month overall survival in 17 patients dosed under a fractionated regimen with concurrent docetaxel.

The pivotal phase 3 ProstACT Global trial (ClinicalTrials.gov NCT06520345) compares TLX591-Tx plus standard of care (abiraterone, enzalutamide or docetaxel) against standard of care alone in PSMA-positive mCRPC patients who progressed on one prior ARPI, with an initial 36-patient safety/dosimetry lead-in (Part 1) followed by a 2:1 randomised expansion (Part 2, target enrolment approximately 490). Part 1 results (reported March 2026) showed an acceptable safety and tolerability profile across all three standard-of-care combination cohorts, with no new safety signals; the main non-haematological toxicities were fatigue, nausea and dry mouth, and haematological toxicity (thrombocytopenia, neutropenia) was transient and manageable. Part 2 is enrolling in Australia, New Zealand, Canada, Türkiye, the UK and other jurisdictions; TLX591 has not yet received marketing authorisation anywhere.