ProstACT Part 1: TLX591-Tx Safety, Dosimetry, and Implications for Part 2

Telix Pharmaceuticals said ProstACT Global Part 1, the safety and dosimetry lead-in for TLX591‑Tx (177Lu rosopatamab tetraxetan), achieved its primary objectives in PSMA-positive mCRPC.

The company described safety and tolerability findings alongside dosimetry and biodistribution readouts intended to inform the Part 2 randomized expansion. It plans to present Part 1 data to the U.S. FDA to seek an IND amendment to progress Part 2 in the U.S.

The release describes Part 1 as dosing 36 patients with TLX591‑Tx as two doses 14 days apart, administered in combination with one of three standard-of-care therapies. Patients were allocated to TLX591‑Tx plus enzalutamide (n=11), TLX591‑Tx plus abiraterone (n=11), or TLX591‑Tx followed by docetaxel (n=14), and the sponsor stated that all participants received both doses per protocol. This configuration was presented as a structured lead-in to support enrollment in the global expansion phase.

Across the combination cohorts, the sponsor stated that an acceptable safety and tolerability profile was observed for TLX591‑Tx (177Lu rosopatamab tetraxetan), with “no new safety signals” reported. Non-hematologic treatment-emergent adverse events were described as almost all Grade 1–2, with the most prevalent events reported as fatigue (53%), nausea (28%), and dry mouth (25%). Hematologic events were characterized as transient and manageable, and the sponsor reported Grade 3–4 thrombocytopenia and neutropenia within the observed event profile. These safety observations were presented as descriptive findings from the Part 1 lead-in.

Dosimetry and imaging readouts were also summarized in the release as meeting the intent of the lead-in evaluation. Lesion dosimetry was described as showing uptake across tumor sites and across all cohorts, with no difference in absorbed dose profile by cohort. For normal tissues, the sponsor reported that radiation exposure to key organs was well below established safety limits, with limited dose to the salivary glands and kidneys. The release additionally stated that no adverse drug–drug interactions were observed that affected targeting, distribution, or clearance, and that pharmacokinetic findings showed sustained activity at 15 days, corroborated by imaging showing prolonged tumor retention. These technical readouts were positioned as sponsor-reported confirmation of biodistribution and dosimetry objectives for Part 1.

Telix said it has already advanced ProstACT into Part 2, described as a 2:1 randomized treatment expansion, in jurisdictions where approvals have been obtained. The announcement specified that Part 2 is enrolling in Australia, New Zealand, and Canada, and has also received regulatory approval to commence in China, Singapore, South Korea, Türkiye, and the United Kingdom. The company also stated it plans to present Part 1 data to the U.S. FDA to seek an IND amendment intended to progress Part 2 in the U.S. These next steps were presented as forward-looking elements following the Part 1 readout.

Key Takeaways:

• The sponsor reported Part 1 completion as a safety/dosimetry lead-in in PSMA-positive mCRPC, using two TLX591‑Tx doses given 14 days apart across three standard-of-care combination cohorts.
• The announcement described no new safety signals, with mostly low-grade non-hematologic events and hematologic events characterized as transient/manageable, alongside reported Grade 3–4 thrombocytopenia and neutropenia.
• The sponsor reported organ radiation exposure below established safety limits, with limited salivary gland and kidney exposure.
• The sponsor also reported imaging consistent with sustained tumor retention at 15 days and said it plans to present Part 1 data to the FDA to seek an IND amendment to progress Part 2 in the U.S.