공시 • Jun 02
Telix Pharmaceuticals Limited Presents Part 1 Data from Prostact Global Phase 3 Study of Tlx591-Tx in Metastatic Castration-Resistant Prostate Cancer
Telix Pharmaceuticals Limited announced the oral presentation of Part 1 safety, dosimetry and pharmacokinetics data from the ProstACT Global Phase 3 Study of TLX591-Tx (lutetium-177 (177Lu) rosopatamab tetraxetan), in metastatic castration-resistant prostate cancer (mCRPC). Results demonstrated that TLX591-Tx, Telix’s lead prostate-specific membrane antigen (PSMA) targeted lutetium rADC therapy candidate, has an acceptable safety and tolerability profile when administered with standard of care (SoC) therapies in mCRPC, with no new safety signals observed. ProstACT Global is an international, multi-center, randomized Phase 3 trial comparing TLX591-Tx, administered as two doses, 14 days apart with SoC (abiraterone, enzalutamide or docetaxel) versus SoC alone. The study is designed to reflect real-world clinical practice and enrolls PSMA-positive mCRPC patients previously treated with one androgen receptor pathway inhibitor (ARPI). Patients were monitored for treatment-emergent adverse events and underwent serial SPECT/CT imaging after TLX591-Tx administration for dosimetry and blood sampling for pharmacokinetics. The primary endpoint was safety and tolerability of TLX591-Tx + SoC. Key secondary endpoints were pharmacokinetics and radiation dosimetry. Data from 36 patients (baseline median PSA: 18.18 ng/mL) who received any study treatment were included: Cohort 1 (11 patients), TLX591-Tx + abiraterone; Cohort 2 (11 patients), TLX591-Tx + enzalutamide; Cohort 3 (14 patients), TLX591-Tx followed by docetaxel. Acceptable safety profile observed across all combination cohorts, tolerability of TLX591-Tx consistent with prior studies. All 36 patients received both doses of TLX591-Tx per protocol. No new safety signals identified. Almost all treatment-emergent non-hematologic events were Grade 1–2, primarily fatigue (53%), nausea (28%) and dry mouth (25%). Hematologic events were transient and manageable: Grade 3 thrombocytopenia (14%) and neutropenia (22%), and Grade 4 thrombocytopenia (31%) and neutropenia (25%) events were in line with the profile expected for this class of therapy and extent of disease. Radiation exposure to key organs was well below established safety limits. Highest absorbed dose observed in liver (range, 1.62-5.08 mGy/MBq), with lower doses received by kidneys (0.336-0.961 mGy/MBq) and salivary glands (0.001-0.104 mGy/MBq). Lesion dosimetry confirmed uptake across tumor sites and across all cohorts. Pharmacokinetics demonstrated sustained activity at Day 15, corroborated by imaging which demonstrated prolonged tumor retention. No evidence of drug-drug interactions impacting TLX591-Tx targeting, distribution or clearance. Telix has initiated Part 2, a 2:1 randomized treatment expansion, in jurisdictions where regulatory approvals have been obtained. ProstACT Global (ClinicalTrials.gov ID: NCT06520345) is an international, multicenter trial in two parts: Part 1, safety and dosimetry lead-in with 36 patients (complete); and Part 2, 2:1 randomized global expansion with an overall target enrollment of approximately 490 patients. Eligible patients must have confirmed progressive mCRPC assessed with a 68Ga-PSMA-11 PET imaging agent (such as Illuccix®, kit for the preparation of gallium-68 (68Ga) gozetotide injection, or Gozellix®, kit for the preparation of gallium-68 (68Ga) gozetotide injection) following prior treatment with one ARPI. The antibody approach demonstrates different targeting and pharmacology to that observed in other PSMA-targeted small molecule radioligand therapies (RLT). In contrast to these therapies, collective long-term follow-up of patients administered with TLX591-Tx has not observed significant acute or delayed kidney toxicity, as the agent is primarily cleared through the liver, a comparatively radioresistant organ, instead of the kidneys. Due to its large molecular weight, TLX591-Tx also demonstrates minimal salivary and lacrimal gland uptake, reducing dry mouth and dry eyes, common adverse effects of existing PSMA-targeted RLTs.