TLX591-Tx Shows Manageable Safety Profile in Prostate Cancer Trial

Part 1 of the ProstACT Global phase 3 study (NCT06520345), a safety and dosimetry lead-in for the investigational therapeutic candidate TLX591-Tx (lutetium-177 (177Lu) rosopatamab tetraxetan), has demonstrated an acceptable safety and tolerability profile with no new safety signals observed in patients with metastatic castration-resistant prostate cancer, according to a news release from the manufacturer, Telix.¹

The phase 1 portion of the study enrolled 36 patients with progressive metastatic castration-resistant prostate cancer who were allocated across 3 treatment cohorts. Eleven patients received TLX591-Tx in combination with enzalutamide (Xtandi), 11 received TLX591-Tx with abiraterone (Zytiga), and 14 received TLX591-Tx followed by docetaxel. All 36 patients successfully completed both doses of TLX591-Tx as required by the protocol, and investigators observed no new safety signals beyond what has been previously documented with this class of therapy.

Trial Design

ProstACT Global is a differentiated phase 3 trial comparing PSMA-targeted 177Lu-rADC therapy administered with standard of care (SOC) versus SOC alone. Telix has already advanced the study into Part 2 – a 2:1 randomized treatment expansion – in Australia, New Zealand, and Canada.

Part 1 data will be presented to the FDA to seek an Investigational New Drug (IND) amendment to progress part 2, a randomized global expansion that will enroll approximately 490 patients in a 2:1 randomization ratio. Eligible patients must have confirmed progressive metastatic castration-resistant prostate cancer as assessed with a 68Ga-PSMA-11 PET imaging agent following prior treatment with one androgen receptor pathway inhibitor.²

“These results reinforce the feasibility of integrating TLX591-Tx with current standard of care therapies for mCRPC, including ARPIs such as enzalutamide or abiraterone, or docetaxel,” Neeraj Agarwal, MD, professor of medicine and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute, Salt Lake City, and ProstACT Global Principal Investigator and Steering Committee member, said in a release. “Hematologic events align with those typically seen in this patient population and therapeutic class, and these cases resolved quickly. The dosimetry profile, along with the low-grade nature of non-hematologic adverse events, further supports the tolerability profile of this investigational therapy,” Agarwal continued.

Safety Findings

The safety profile of TLX591-Tx across the combination cohorts remained acceptable, with tolerability consistent with prior studies of the agent. Almost all treatment-emergent non-hematologic events were grade 1 or 2 in severity. The most commonly reported non-hematologic side effects were fatigue, which occurred in 53% of patients, nausea in 28%, and dry mouth in 25%.

Hematologic events observed in the study were transient and manageable. Grade 3 thrombocytopenia occurred in 14% of patients and grade 3 neutropenia in 22%. Grade 4 thrombocytopenia was observed in 31% of patients and grade 4 neutropenia in 25%. Investigators noted that these findings were in line with the expected profile for this class of therapy and consistent with the extent of disease in this patient population.

Radiation Exposure

Dosimetry and biodistribution data from the trial showed that radiation exposure to key organs remained well below established safety limits. There was limited radiation dose delivered to the salivary glands and kidneys, which are often areas of concern with radiopharmaceutical therapies. Lesion dosimetry demonstrated uptake across tumor sites in all treatment cohorts, indicating effective targeting of cancer cells.

Pharmacokinetic analysis revealed sustained activity at 15 days, a finding corroborated by imaging that demonstrated prolonged tumor retention of the therapeutic agent. Importantly, researchers found no evidence of drug-drug interactions that impacted TLX591-Tx targeting, distribution, or clearance when combined with the standard therapies.

The ProstACT Global trial continues to evaluate the potential of TLX591-Tx in combination with established treatments for metastatic castration-resistant prostate cancer, with the randomized expansion phase now underway.

REFERENCE

1. ProstACT Global Phase 3 Study (Part 1) Achieves Primary Objectives. News release. Accessed March 10, 2026. https://tinyurl.com/3mum54tm

2. The Study of 177Lu-TLX591 Plus SOC Versus SOC Alone in Patients With mCRPC (ProstACT Global). ClinicalTrials.gov ID NCT06520345. Accessed March 10, 2026. https://clinicaltrials.gov/study/NCT06520345