The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting once again brought together the latest advances in cancer research from around the world. Among the most closely watched areas was radioligand therapy (RLT) for prostate cancer. During the meeting, the ProstACT Global 3 study team presented the first Part 1 results from its Phase III trial, focusing on the safety and dosimetry of TLX591 (¹⁷⁷Lu-rosopatamab tetraxetan). These findings provide early evidence supporting the feasibility of integrating TLX591 with standard-of-care treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), while also demonstrating encouraging preliminary efficacy signals. Oncology Frontier–UroStream invited Prof. Pedro C. Barata, Global Principal Investigator of the ProstACT study from the Seidman Cancer Center, to discuss the mechanism of action, dosing strategy, safety profile, and potential role of TLX591 in the evolving treatment landscape of mCRPC.
Oncology Frontier–UroStream
The ProstACT Global 3 study investigates TLX591, a PSMA-targeted radiolabeled antibody. Compared with other radioligand therapies currently available, what distinguishes TLX591? How do you view its design concept and clinical potential?
Prof. Pedro C. Barata
The ProstACT Global 3 study evaluates TLX591, a radiolabeled monoclonal antibody targeting prostate-specific membrane antigen (PSMA) and labeled with lutetium-177 (¹⁷⁷Lu). Compared with currently available radioligand therapies, one of its defining characteristics is that it is antibody-based, resulting in a substantially larger molecular size than small-molecule radioligands.
The treatment follows a fixed dosing schedule consisting of two administrations separated by 14 days, completing the therapeutic course within a short timeframe. TLX591 has a relatively long biological half-life of approximately 5.6 days, is eliminated primarily through the gastrointestinal tract, and remains in systemic circulation for an extended period.
Imaging studies also demonstrate prolonged retention of the agent within tumor lesions, giving TLX591 a unique pharmacokinetic and biodistribution profile. The central question is whether these favorable pharmacokinetic properties will ultimately translate into superior clinical outcomes.
Another important advantage is the convenience of the treatment regimen. Patients receive two fixed doses of approximately 76 mCi administered 14 days apart, after which treatment is complete while remaining integrated with standard therapy. This standardized approach makes the regimen practical and highly feasible for routine clinical implementation.
Oncology Frontier–UroStream
The Phase III data presented at ASCO primarily focused on safety and dosimetry. How safe is TLX591 when combined with standard therapy, and does it appear suitable for long-term clinical use?
Prof. Pedro C. Barata
The data presented at ASCO represent Part 1 of the ProstACT Global 3 study, which serves as the safety and dosimetry lead-in phase.
Patients received TLX591 using a fixed-dose regimen of 76 mCi administered twice, 14 days apart, in combination with androgen receptor pathway inhibitors (ARPIs) such as abiraterone or enzalutamide, or sequentially with docetaxel as part of an integrated standard-of-care treatment strategy.
From a safety perspective, adverse events can be broadly categorized into non-hematologic and hematologic toxicities.
Non-hematologic adverse events were mainly fatigue and mild gastrointestinal symptoms. These events were relatively common but were generally transient and of low severity. Importantly, no treatment-related deaths were reported, and the incidence of serious treatment-related adverse events remained low.
Regarding hematologic toxicity, the principal events included thrombocytopenia, neutropenia, anemia, and lymphopenia, with some cases reaching Grade 3 or higher severity. Platelet counts typically reached their nadir approximately 43 days after treatment, but recovery was relatively rapid, returning to approximately Grade 1 levels within about 15 days.
Supportive care requirements remained limited. The use of platelet transfusions and granulocyte colony-stimulating factor (G-CSF) was generally low, occurring in only a small proportion of patients.
Overall, the safety profile appears manageable and largely reversible, providing a strong foundation for combining TLX591 with standard therapies.
From a dosimetry perspective, SPECT imaging demonstrated sustained tumor retention of the radiopharmaceutical, supporting the proposed mechanism of prolonged tumor irradiation. Taken together, the Part 1 results are encouraging and provide the rationale for expanding evaluation in larger patient populations.
Oncology Frontier–UroStream
As a global Phase III study, what role do you envision for TLX591 in the future management of mCRPC? What key questions will subsequent studies seek to answer?
Prof. Pedro C. Barata
Radioligand therapy is advancing rapidly across solid tumors, particularly in prostate cancer. Several agents have already received regulatory approval, and many more are expected to enter clinical practice in the coming years.
The significance of the ProstACT study lies in determining whether TLX591 can be safely and effectively integrated with current standard-of-care therapies, including androgen receptor pathway inhibitors and subsequent docetaxel treatment. Early-phase findings have already provided encouraging evidence supporting this treatment strategy.
The next critical step is to determine whether these promising early observations translate into improved outcomes in larger populations. The primary focus will be on whether TLX591 can significantly improve progression-free survival (PFS) compared with standard treatment alone, while overall survival (OS) remains another key secondary endpoint.
Should the final Phase III results prove positive, TLX591 has the potential to become an integral component of standard treatment for patients with metastatic castration-resistant prostate cancer, expanding the current therapeutic arsenal.
Looking ahead, additional studies may explore its use in earlier disease settings, including patients who have not yet received ARPI therapy. As our understanding of TLX591 continues to evolve, its place within the overall treatment paradigm for prostate cancer will become increasingly well defined.
Expert Profile
- Global Principal Investigator, ProstACT Global 3 Study
- Genitourinary medical oncologist at the Seidman Cancer Center
- Internationally recognized expert in advanced prostate cancer and genitourinary malignancies
- Research interests include radioligand therapy, targeted therapies, immunotherapy, and precision medicine for metastatic prostate cancer
- Principal investigator in multiple international clinical trials evaluating novel therapeutic strategies for metastatic castration-resistant prostate cancer (mCRPC)
