FDA OKs ProstACT Trial Part 2 Protocol for Metastatic Prostate Cancer

The FDA has confirmed alignment with the trial sponsor on advancing part 2 of the ProstACT Global phase 3 trial (NCT06520345) of TLX591-Tx (lutetium-177 [¹⁷⁷Lu] rosopatamab tetraxetan) into the United States, following a type B meeting in which the agency reviewed part 1 safety and dosimetry data and the part 2 protocol design, Telix Pharmaceuticals announced in a news release.¹

The FDA confirmed that part 1 lead-in safety data are sufficient to enable US initiation of part 2 comparison of TLX591-Tx with standard of care (SOC) in metastatic castration-resistant prostate cancer (mCRPC). Alignment was reached on the clinical trial protocol, statistical analysis plan, and ongoing safety monitoring plan.

Initiation of part 2 in the US remains subject to FDA review of an investigational new drug (IND) amendment, which Telix indicated will also be aligned with a pending regulatory submission to initiate the study in Europe.

Trial Design and Background

ProstACT Global is an international, multicenter phase 3 trial comparing the prostate-specific membrane antigen (PSMA)-targeted ¹⁷⁷Lu antibody-drug conjugate (rADC) therapy in combination with SOC alone in patients with mCRPC. Part 1 was a 36-patient safety and dosimetry lead-in, whereas part 2 is a 2:1 randomized global expansion targeting approximately 490 patients. Eligible patients must have confirmed progressive mCRPC as assessed with a ⁶⁸Ga-PSMA-11 PET imaging agent following prior treatment with 1 androgen receptor pathway inhibitor (ARPI). In -art 2, TLX591-Tx is administered in 2 doses 14 days apart in combination with 1 of 3 SOC therapies: abiraterone (Zytiga), enzalutamide (Xtandi), or docetaxel.

Part 1 Safety Data

Part 1 of ProstACT Global enrolled 36 patients across 3 combination cohorts, 11 receiving TLX591-Tx with enzalutamide, 11 with abiraterone, and 14 with docetaxel followed by TLX591-Tx. All 36 patients completed both planned doses of TLX591-Tx without emergent, unexpected toxicity signals.²

Nonhematologic adverse events were predominantly grade 1 or 2. The most common were fatigue (53% of patients), nausea (28%), and xerostomia (25%). Hematologic events were transient; grade 3 thrombocytopenia occurred in 14% of patients and grade 3 neutropenia in 22%, while grade 4 thrombocytopenia was observed in 31% and grade 4 neutropenia in 25%. Investigators characterized these findings as consistent with the expected profile for the regimen.

Dosimetry and biodistribution data indicated that radiation exposure to key organs remained well below established safety limits, with limited dose received in the salivary glands and kidneys. Lesion dosimetry demonstrated tumor uptake across all treatment cohorts, whereas pharmacokinetic analysis revealing sustained activity at 15 days and no evidence of drug-drug interactions affecting TLX591-Tx targeting, distribution, or clearance when combined with the standard therapies.

Differentiated Profile Among PSMA-Targeted Agents

As an antibody-based agent, TLX591-Tx is primarily cleared through the liver rather than the kidneys, reducing toxicities seen with small molecule radioligand therapies targeting PSMA. Long-term patient follow-up has not observed significant acute or delayed kidney toxicity with TLX591-Tx. It also results in minimal salivary and lacrimal gland uptake, potentially reducing the xerostomia and dry eye that are typical adverse effects of other radioligand therapies.

“TLX591-Tx has the potential to redefine how radiopharmaceutical therapy is integrated into clinical practice,” Neeraj Agarwal, MD, professor of medicine and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute and ProstACT Global principal investigator, stated in the news release. He added that its 2-week treatment course makes it possible to include it with an existing regimen with minimal interruption.¹

The FDA’s confirmation has enabled submission of the IND amendment for part 2 initiation in the US. Part 2 is currently enrolling in regions where regulatory approval has been granted, including Australia, New Zealand, and Canada.

REFERENCES

1. FDA Alignment to Advance ProstACT Global Phase 3 Trial. News release. Telix Pharmaceuticals. July 1, 2026. Accessed July 6, 2026. https://tinyurl.com/bdfudma9

2. ProstACT Global Phase 3 Study (Part 1) Achieves Primary Objectives. News release. Accessed July 6, 2026. https://tinyurl.com/3mum54tm