Telix Clears Phase 3 Safety Hurdle for First-in-Class Prostate Cancer Therapy

Telix Pharmaceuticals (ASX: TLX) has announced that Part 1 of its Telix ProstACT Global Phase 3 study has achieved its primary objectives, demonstrating an acceptable safety and tolerability profile with no new safety signals observed. The study evaluates TLX591-Tx, a first-in-class lutetium radio antibody-drug conjugate (rADC) therapy targeting PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) patients. Part 2 randomised expansion is already enrolling in Australia, New Zealand, and Canada, with regulatory approvals secured in China, Singapore, South Korea, Türkiye, and the United Kingdom.

All 36 patients across three cohorts completed both doses per protocol, with results consistent with prior clinical studies of TLX591-Tx. The Phase 3 progression de-risks the clinical pathway toward potential FDA approval, whilst multi-country regulatory clearances signal a global commercial opportunity in a competitive first and second-line mCRPC treatment landscape.

Telix’s ProstACT Global Phase 3 achieves key safety milestones

Part 1 of the Telix ProstACT Global Phase 3 study has met its primary objectives, confirming the safety profile, biodistribution, and dosimetry of TLX591-Tx administered in two doses 14 days apart. The investigational therapy, a lutetium-177 radio antibody-drug conjugate, was tested in combination with three standard of care therapies: abiraterone, enzalutamide, or docetaxel. The patient population comprised PSMA-positive mCRPC patients previously treated with one androgen receptor pathway inhibitor (ARPI).

Part 2, a 2:1 randomised treatment expansion targeting approximately 490 patients, is already underway in approved jurisdictions. The company has stated that Part 1 data will be presented to the United States Food and Drug Administration (FDA) to seek an Investigational New Drug (IND) amendment to progress Part 2 in the U.S. This regulatory engagement represents a critical next step in expanding the study’s geographic reach and accelerating the pathway toward potential marketing authorisation.

TLX591-Tx has not received marketing authorisation in any jurisdiction. The announcement positions Telix to advance its first-in-class rADC therapy through a differentiated Phase 3 trial design that compares PSMA-targeted therapy administered with standard of care versus standard of care alone, reflecting current global clinical practice.

Understanding radio antibody-drug conjugates in prostate cancer treatment

A radio antibody-drug conjugate (rADC) is a targeted therapy that combines a radioactive isotope with an antibody designed to bind to specific cancer cell markers. TLX591-Tx uses lutetium-177 attached to an antibody that targets PSMA, a protein found on prostate cancer cells. The antibody delivers radiation directly to tumour sites, aiming to destroy cancer cells whilst limiting damage to surrounding healthy tissue.

TLX591-Tx differs from existing PSMA-targeted small molecule radioligand therapies in its biodistribution and clearance profile. The antibody approach is primarily cleared through the liver rather than the kidneys, reducing the risk of kidney toxicity observed with some existing therapies. Additionally, due to its large molecular weight, TLX591-Tx demonstrates minimal salivary and lacrimal gland uptake, potentially reducing common side effects such as dry mouth and dry eyes associated with existing PSMA-targeted radioligand therapies.

This differentiated safety profile could position TLX591-Tx favourably in a competitive market, particularly in first and second-line mCRPC treatment where improved tolerability may support broader patient eligibility and sustained treatment duration. The therapy addresses an unmet medical need in a patient population that continues to require improved treatment options despite recent clinical advances.

Safety and dosimetry results across treatment cohorts

Tolerability profile

ProstACT Global Part 1 dosed 36 patients across three cohorts. Cohort 1 enrolled 11 patients receiving TLX591-Tx in combination with enzalutamide, Cohort 2 enrolled 11 patients receiving TLX591-Tx with abiraterone, and Cohort 3 enrolled 14 patients receiving TLX591-Tx followed by docetaxel. All patients received both doses of TLX591-Tx per protocol.

Almost all treatment-emergent non-hematologic events were Grade 1 or Grade 2. The most prevalent non-hematologic adverse events were fatigue (53%), nausea (28%), and dry mouth (25%). Hematologic events were transient and manageable, with similar rates of recovery across all patient cohorts. Grade 3 thrombocytopenia occurred in 14% of patients and Grade 3 neutropenia in 22%, whilst Grade 4 thrombocytopenia was observed in 31% and Grade 4 neutropenia in 25%. These events aligned with the profile expected for this class of therapy and extent of disease. The results are consistent with prior clinical studies of TLX591-Tx.

Dosimetry and biodistribution findings

Radiation exposure to key organs was well below established safety limits referenced in published literature. Limited radiation dose was observed in salivary glands and kidneys, supporting the liver-clearance mechanism described in the study design. Lesion dosimetry demonstrated uptake across tumour sites and all cohorts, with no difference in absorbed dose profile across the three treatment combinations.

Pharmacokinetics demonstrated sustained activity at 15 days, corroborated by imaging which showed prolonged tumour retention. Importantly, there was no evidence of drug-drug interactions impacting TLX591-Tx targeting, distribution, or clearance. This finding supports the feasibility of combining TLX591-Tx with contemporary standard of care therapies, including ARPIs such as enzalutamide or abiraterone, or chemotherapy such as docetaxel. The absence of drug-drug interactions is particularly relevant for patients with mCRPC who often receive multiple lines of therapy.

Trial design and pathway to FDA engagement

The Telix ProstACT Global Phase 3 trial is designed to compare PSMA-targeted lutetium-177 rADC therapy administered with standard of care versus standard of care alone. This design reflects current global clinical practice, where combination approaches are increasingly used in mCRPC management. Part 1 served as a safety and dosimetry lead-in, whilst Part 2 represents a 2:1 randomised global expansion targeting approximately 490 patients.

Eligible patients must have confirmed progressive mCRPC assessed with a 68Ga-PSMA-11 PET imaging agent (such as Illuccix or Gozellix) following prior treatment with one ARPI. The imaging requirement ensures that enrolled patients have PSMA-positive disease, aligning treatment with the mechanism of action of TLX591-Tx.

Telix has stated that Part 1 data will be presented to the FDA to seek an IND amendment for Part 2 expansion in the U.S. This regulatory engagement is positioned to occur at the earliest opportunity, whilst Part 2 continues to enrol patients in jurisdictions where clinical trial initiation has already been approved. The multi-country regulatory strategy supports parallel development across major markets.

David N. Cade, MD, Group Chief Medical Officer

“These results build on prior findings and highlight the potential for TLX591-Tx 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.”

Clinical validation and next steps

The Principal Investigator for the ProstACT Global study has stated that results reinforce the feasibility of integrating TLX591-Tx with current standard of care therapies for mCRPC. Hematologic events aligned with those typically seen in this patient population and therapeutic class, and resolved quickly. The dosimetry profile, combined with the low-grade nature of non-hematologic adverse events, further supports the tolerability profile of the investigational therapy.

Telix’s immediate next steps include FDA engagement to seek IND amendment for Part 2 U.S. expansion, whilst continuing to advance enrolment in regions where the study is already approved. Part 2 has received regulatory approval to commence in the following jurisdictions:

1. Australia
2. New Zealand
3. Canada
4. China
5. Singapore
6. South Korea
7. Türkiye
8. United Kingdom

Telix’s existing precision medicine franchise includes Illuccix, approved in multiple markets globally, and Gozellix, approved by the U.S. FDA. This commercial foundation positions the company to leverage existing diagnostic infrastructure to support potential future commercialisation of TLX591-Tx, pending regulatory approval. TLX591-Tx has not received marketing authorisation in any jurisdiction.

Neeraj Agarwal, MD, Principal Investigator

“These results reinforce the feasibility of integrating TLX591-Tx with current standard of care therapies for mCRPC, including ARPIs such as enzalutamide or abiraterone, or docetaxel.”

Successful FDA engagement could accelerate the U.S. clinical development timeline, whilst multiple jurisdictions already approved for Part 2 enrolment position Telix for global commercial launch upon regulatory approval. The differentiated Phase 3 design comparing combination therapy versus standard of care alone represents a pragmatic trial structure aligned with contemporary clinical practice in advanced prostate cancer management.

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