Lutetium-177 rosopatamab tetraxetan meets primary safety objectives in phase 3 trial for mCRPC

Early results from the phase 3 ProstACT Global trial (NCT06520345) suggest that lutetium-177 (¹⁷⁷Lu) rosopatamab tetraxetan (TLX591-Tx), an investigational PSMA-targeted lutetium radio antibody-drug conjugate (¹⁷⁷Lu-rADC), may be feasibly combined with standard of care (SOC) therapies for patients with metastatic castration-resistant prostate cancer (mCRPC).¹

The agent met the primary safety objectives of the safety and dosimetry lead-in portion of the study by demonstrating an acceptable safety and tolerability profile when administered in combination with either enzalutamide (Xtandi), abiraterone (Zytiga), or when followed by docetaxel in patients with mCRPC who received prior treatment with an androgen receptor pathway inhibitor (ARPI).

“These results reinforce the feasibility of integrating [lutetium-177 rosopatamab tetraxetan] with current standard of care therapies for mCRPC, including ARPIs such as enzalutamide or abiraterone, or docetaxel,” said ProstACT Global principal investigator Neeraj Agarwal, MD, FASCO, professor of medicine and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute in Salt Lake City, Utah. “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.”

ProstACT Global is an international, multicenter phase 3 trial designed in 2 parts: an initial safety and dosimetry lead-in followed by a randomized treatment expansion comparing lutetium-177 rosopatamab tetraxetan plus SOC vs SOC alone. The completed lead-in phase included 36 patients who were allocated to receive lutetium-177 rosopatamab tetraxetan plus enzalutamide, lutetium-177 rosopatamab tetraxetan plus abiraterone, or lutetium-177 rosopatamab tetraxetan followed by docetaxel. All patients received 2 doses of lutetium-177 rosopatamab tetraxetan administered 14 days apart.

Across cohorts, nearly all treatment-emergent nonhematologic adverse events were grade 1 or 2. The most frequently reported events were fatigue (53%), nausea (28%), and xerostomia (25%). Hematologic toxicities were transient, manageable, and consistent with the expected safety profile. Telix also reported similar recovery rates across treatment cohorts.

Grade 3 thrombocytopenia occurred in 14% of patients and grade 3 neutropenia occurred in 22% of patients. Grade 4 thrombocytopenia and neutropenia occurred in 31% and 25% of patients, respectively.

Dosimetry analyses indicated consistent tumor uptake across lesions and treatment cohorts. Radiation exposure to organs at risk—including kidneys and salivary glands—remained below established safety limits, and imaging demonstrated sustained tumor retention of the radiolabeled antibody up to 15 days after administration.

Importantly, no adverse drug–drug interactions were observed when lutetium-177 rosopatamab tetraxetan was administered with ARPIs or chemotherapy

Based on these findings, the trial has advanced to its second phase in jurisdictions where the trial has received approval from health authorities. Telix plans to submit data from part 1 of the study to the FDA in order to obtain an Investigational New Drug amendment to proceed with part 2 in the US.

Part 2 of the study consists of a 2:1 randomized expansion, expecting to enroll approximately 490 patients globally. To be eligible for enrollment, patients need to have confirmed progressive mCRPC per imaging with a ⁶⁸Ga-PSMA-11 PET imaging agent following prior treatment with 1 ARPI.

“Despite advances in clinical practice, men with advanced prostate cancer still need improved first and second line treatment options,” concluded David N. Cade, MD, Group Chief Medical Officer for Telix, in the news release.¹ “These results build on prior findings and highlight the potential for [lutetium-177 rosopatamab tetraxetan] in combination with contemporary standard of care, to become a new first-line option for patients facing this aggressive disease. We are encouraged by the data and look forward to engaging with the FDA at the earliest opportunity, while continuing to advance enrollment in part 2 in regions where clinical trial initiation has already been approved.”

REFERENCE

1. ProstACT Global Phase 3 Study (Part 1) Achieves Primary Objectives. News release. Telix Pharmaceuticals. March 9, 2026. Accessed March 12, 2026. https://telixpharma.com/news-views/prostact-global-phase-3-study-part-1-achieves-primary-objectives/