Telix announces that the first patient has been dosed in the Company’s Phase III ProstACT GLOBAL study of its investigational prostate-specific membrane antigen (PSMA) targeting radio-antibody drug conjugate (rADC) therapy, TLX591 (177Lu-rosopatamab tetraxetan). TLX591 is a rADC composed of a high-specificity PSMA-targeting antibody, chelator linker, and cytotoxic lutetium (177Lu) payload. The PSMA-targeted monoclonal antibody (mAb) approach offers significantly different targeting and pharmacology to anti-PSMA small molecules.
ProstACT GLOBAL is the first Phase III trial to evaluate TLX591 in adult patients with PSMA-positive metastatic castrate-resistant prostate cancer (mCRPC) administered together with Standard of Care (SoC, androgen receptor inhibition or taxanes) versus SoC alone. Integration with current real-world SoC differentiates ProstACT GLOBAL from other PSMA studies and reflects Telix’s continued innovation in prostate cancer care and commitment to patient outcomes.
To date, 242 patients have been treated across eight Phase I and II studies of TLX591, including Telix’s ProstACT SELECT study (ClinicalTrials.gov ID: NCT04786847), which confirmed the clinical validity of Telix’s optimal fractionated dosing and product safety profile. Prior published Phase II (single-arm) study data reported a 42.3 month overall survival (OS) and an acceptable safety profile when delivered under a fractionated dosing regimen administered concurrently with docetaxel chemotherapy. Compared to other radioligand therapies, collective long-term follow-up of patients administered with TLX591 has not observed significant acute or delayed nephrotoxicity due to the hepatic clearance of the agent.
Preliminary data from the recently completed ProstACT SELECT study demonstrated high on-target PSMA tumour-binding and radiation delivery to bone, nodal, and visceral metastases while minimising uptake and toxicity concerns in kidney, salivary glands, and lacrimal glands. This differentiated biodistribution is significant when compared to small molecule diagnostic and therapeutic PSMA agents, as uptake may not be strictly limited to cancerous tissue. The SELECT results also confirm the clinical advantage of the short, simple treatment regimen of two doses administered 14 days apart, while demonstrating the longer retention, internalisation, and potential therapeutic benefits of the 177Lu-labelled PSMA-antibody targeting approach.
ProstACT GLOBAL builds on the previous Phase I and II studies of TLX591, including ProstACT SELECT. It is a multinational, multicenter, prospective, randomised, controlled, open label Phase III study designed to investigate and confirm the patient benefits and risks associated with TLX591 administered together with SoC, compared to SoC alone. ProstACT GLOBAL has an overall target enrolment of ~400 patients, with the first dose successfully administered at GenesisCare’s centre at the St John of God Hospital Murdoch campus in Australia.
The study is expected to expand internationally, subject to regulatory approvals, including in Europe and the United States where Telix’s investigational new drug (IND) application remains on track for filing with the US Food and Drug Administration (FDA) in Q4 2023. The planned US arm of the study will also incorporate a run-in to bridge manufacturing data to a new commercial-scale process. An interim analysis is expected after the first 120 patients.
Nat Lenzo, MD, GenesisCare Group Clinical Director Theranostics and Principal Investigator on the ProstACT GLOBAL study commented, “Recent studies, including ProstACT SELECT, have further advanced the development of this antibody-based PSMA therapy for prostate cancer patients. We have been encouraged with the safety profile, tolerability and early efficacy observed in our previous and ongoing studies, in particular for symptom control. It’s an important step forward for patients to see this investigational therapy enter a Phase III study.”
Dr Colin Hayward, Group Chief Medical Officer of Telix said, “Dosing a first patient in the ProstACT GLOBAL study is a significant milestone for Telix and will help build on an already extensive data set for this product candidate. The current TLX591 experience underlines the potential benefits of an antibody-based approach in combination with real world standards of care, including physician choice of ARPI[5] or taxane. As we take this potential first-in-class rADC candidate into a large, mid-stage patient population for the first time, we would like to thank Professor Lenzo and his clinical team, as well as the patients who will contribute to the study.”