Lutetium-177 Rosopatamab Tetraxetan Plus SOC Meets Primary Safety End Point in PSMA+ mCRPC

Lutetium-177 (¹⁷⁷Lu) rosopatamab tetraxetan (TLX591-Tx) plus standard-of-care (SOC) therapies met the primary objectives of part 1 of the phase 3 ProstACT Global study (NCT06520345) by demonstrating tolerability with no new safety signals observed in patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who previously received an androgen receptor pathway inhibitor (ARPI).¹

Part 1 of ProstACT included 36 patients, divided into 3 cohorts: ¹⁷⁷Lu rosopatamab tetraxetan plus enzalutamide (Xtandi; n = 11); ¹⁷⁷Lu rosopatamab tetraxetan plus abiraterone (Zytiga; n = 11); and ¹⁷⁷Lu rosopatamab tetraxetan followed by docetaxel (n = 14).² Topline data from part 1 revealed that the tolerability profile of ¹⁷⁷Lu rosopatamab tetraxetan was supported by dosimetry and low-grade nonhematologic adverse effects (AEs). The safety profile was acceptable across the combination cohorts, and the tolerability of ¹⁷⁷Lu rosopatamab tetraxetan was consistent with findings from prior studies. All 36 patients received both doses of ¹⁷⁷Lu rosopatamab tetraxetan per the study protocol, and no new safety signals were reported.

“These results reinforce the feasibility of integrating [¹⁷⁷Lu rosopatamab tetraxetan] with current standard-of-care therapies for mCRPC, including ARPIs such as enzalutamide or abiraterone or docetaxel,” Neeraj Agarwal, MD, FASCO, Presidential Endowed Chair of Cancer Research, professor of medicine, and director of the Genitourinary Oncology Program and the Center of Investigational Therapeutics at Huntsman Cancer Institute in Salt Lake City, Utah, stated in a news release.¹ “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 nonhematologic AEs, further supports the tolerability profile of this investigational therapy.”

How was ProstACT Global designed?

ProstACT enrolled patients with PSMA-positive mCRPC who experienced disease progression following treatment with their first ARPI.^2,3 Eligible patients also needed to be at least 18 years old, have an ECOG performance status of 2 or less, and have an estimated life expectancy of at least 6 months.³

Part 1 of ProstACT consisted of a safety and dosimetry lead-in, during which patients received 2 doses of ¹⁷⁷Lu rosopatamab tetraxetan at 76 mCi, 14 days apart, in combination with SOC abiraterone, enzalutamide, or docetaxel.² Part 2, the randomized expansion portion, plans to enroll approximately 490 patients who will be randomly assigned 2:1 to receive an investigational combination or SOC therapy with either an ARPI or docetaxel.

The primary end point in part 1 was safety and tolerability. The primary end point in part 2 is radiographic progression-free survival per blinded independent central review. Secondary end points include overall survival, objective response rate, and time to first symptomatic skeletal event.

What were ProstACT’s additional safety data?

Further safety data showed that no adverse drug-drug interactions were observed with the ¹⁷⁷Lu rosopatamab tetraxetan combinations.¹ Across all 3 cohorts, the most common any-grade nonhematologic treatment-emergent AEs (TEAEs) included fatigue (53%), nausea (28%), dry mouth (25%), and diarrhea (22%). The most common any-grade hematologic TEAEs included thrombocytopenia (78%), neutropenia (64%), and anemia (44%).² These hematologic AEs were in line with the profile expected for the agent class of ¹⁷⁷Lu rosopatamab tetraxetan, according to Telix.

In the news release, Telix, the drug’s developer, noted that the study has advanced into part 2 in jurisdictions where the clinical trial has obtained approval from health authorities.¹ Data from part 1 will be presented to the FDA to seek an investigational new drug amendment to progress part 2 in the US.

“Despite advances in clinical practice, men with advanced prostate cancer still need improved first- and second-line treatment options,” David N. Cade, MD, group chief medical officer at Telix, added in the release. “These results build on prior findings and highlight the potential for [¹⁷⁷Lu rosopatamab tetraxetan], in combination with contemporary SOC, 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.”

References

1. ProstACT Global phase 3 study (Part 1) achieves primary objectives. News release. Telix. March 10, 2026. Accessed March 12, 2026. https://telixpharma.com/news-views/prostact-global-phase-3-study-part-1-achieves-primary-objectives/
2. TLX591-Tx ProstACT Global phase 3 study (NCT06520345). Part 1 Results: safety and dosimetry. Telix Therapeurics. March 10, 2026. Accessed March 12, 2026. https://telixpharmaceuticals.gcs-web.com/static-files/138e45b1-4092-4ed9-80b8-6114bc56a3ed
3. The study of 177Lu-TLX591 plus SOC versus SOC alone in patients with mCRPC (ProstACT Global). ClinicalTrials.gov. Updated July 10, 2025. Accessed March 12, 2026. https://clinicaltrials.gov/study/NCT06520345