Pedro Barata, MD, highlights phase 3 data on 177Lu-rosopatamab tetraxetan in mCRPC

In the following video, Pedro C. Barata, MD, MSc, FACP, discusses preliminary findings from the phase 3 ProstACT Global study (NCT06520345) evaluating ¹⁷⁷Lu-rosopatamab (TLX591-Tx) in combination with standard-of-care therapy for patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after prior androgen receptor pathway inhibitor (ARPI) treatment. These results were presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

According to Barata, the ProstACT Global trial was designed to address a common clinical dilemma in mCRPC: selecting the optimal treatment strategy after progression on an ARPI. As he explained, treatment patterns vary geographically, with ARPI switching remaining common in the US, while chemotherapy—particularly docetaxel—is more frequently used in other regions. The phase 3 study was structured to reflect these real-world practices, evaluating ¹⁷⁷Lu-rosopatamab in combination with either abiraterone (Zytiga), enzalutamide (Xtandi), or docetaxel. The trial includes a lead-in portion followed by a randomized phase comparing ¹⁷⁷Lu-rosopatamab plus standard of care vs standard of care alone, with radiographic progression-free survival serving as the primary end point and overall survival as a key secondary end point.

At ASCO 2026, investigators presented results from part 1, the lead-in phase of the study. Among 36 treated patients with prostate-specific membrane antigen–positive mCRPC, the combination demonstrated a manageable safety and tolerability profile across all treatment cohorts. No new safety signals were identified, and treatment-emergent adverse events were largely transient and manageable. Hematologic toxicities, including thrombocytopenia, neutropenia, and lymphopenia, were the most common adverse events, while nonhematologic toxicities were predominantly low grade. Notably, xerostomia was infrequent and limited to grade 1 events, and no grade 5 treatment-related adverse events were reported.

The study also generated encouraging dosimetry and pharmacokinetic data. Investigators observed relatively low radiation exposure to the salivary glands and kidneys, with absorbed doses remaining below recommended thresholds. Serial imaging demonstrated prolonged tumor retention of ¹⁷⁷Lu-rosopatamab through 15 days after administration, with imaging showing prolonged tumor retention. According to Barata, these findings support the feasibility and tolerability of combining the radioligand therapy with standard systemic treatments and provide the rationale for continued enrollment and evaluation in the ongoing randomized portion of ProstACT Global.

REFERENCE

1. Barata P, Tincknell G, Gill DM, et al. Safety and dosimetry of 177Lu-rosopatamab tetraxetan plus SoC in patients with metastatic castration-resistant prostate cancer: preliminary results from part 1 of phase 3 ProstACT Global study. J Clin Oncol. 2026;44(suppl 17):LBA5009. doi:10.1200/JCO.2026.44.17_suppl.LBA5009