On May 30, 2024 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported additional positive data from the ProstACT SELECT trial ("SELECT") of TLX591 (177Lu rosopatamab tetraxetan), a lutetium-labelled rADC therapy for the treatment of adult patients with PSMA-positive metastatic castrate-resistant prostate cancer (mCRPC) (Press release, Telix Pharmaceuticals, MAY 30, 2024, View Source [SID1234643881]). SELECT is a radiogenomics study intended to evaluate lesion concordance between 68Ga (gallium)-based PSMA-PET[4] imaging and TLX591 dosimetry for the purpose of validating PET imaging for patient selection for rADC therapy. The Company has previously reported final safety data from this study3.
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The study has reported a median rPFS of 8.8 months, representing an encouraging signal of the potential efficacy of TLX591 in this patient population. The evaluable sample size for rPFS comprised 23 patients with previously treated, progressive mCRPC and who received two 76 mCi intravenous (IV) infusions of TLX591, 14 days apart[5]. The SELECT trial included a heterogeneous population of low, medium and high disease burden patients to facilitate imaging cross-comparison, with the majority having undergone two prior lines of therapy.
Nat Lenzo, MD, Nuclear Oncologist and General Internal Medicine Physician and lead recruiter onto the SELECT trial, commented, "We are encouraged by this rPFS result, which compares favourably to small molecule radioligand therapy (RLT) Phase I and II studies at similar stages of development[6]. This is a compelling signal of the potential efficacy of TLX591 in this heavily pre-treated population. The results further support the development of this candidate in an earlier mCRPC patient population which is the focus of the ProstACT GLOBAL[7] Phase III trial and where there remains significant unmet need for effective treatment."
Dr David N. Cade, MD, Group Chief Medical Officer at Telix, stated, "TLX591 is a radio-ADC with significant potential advantages compared to small molecule radiopharmaceuticals in treating prostate cancer. TLX591 is differentiated by a patient-friendly dosing regimen with far lower cumulative radiation exposure compared to small molecule radioligand therapies[8]. This positive signal of efficacy from SELECT builds on prior studies that demonstrated the potential for TLX591 to deliver improved quality of life and durable tumour control in this advanced patient population[9]."
TLX591 is being further evaluated in the Phase III ProstACT GLOBAL trial in first and second line mCRPC, which is now preparing to enrol patients at its first U.S. sites. This innovative trial design allows physicians a choice of androgen receptor inhibition or docetaxel chemotherapy, thus integrating with real-world standard of care, reflective of Telix’s continued innovation in prostate cancer care and commitment to patient outcomes.
About TLX591
TLX591 (INN: lutetium Lu 177 rosopatamab tetraxetan) is Telix’s lead investigational radio antibody-drug conjugate (rADC) for the treatment of mCRPC, composed of a high-specificity PSMA-targeting antibody, chelator linker, and cytotoxic lutetium (177Lu) payload. TLX591 is administered intravenously under a two-dose fractionated regimen, potentially enabling the delivery of a highly targeted and potent dose with improved off-target organ radiation exposure. The mAb-based approach may offer distinct advantages in selectivity, internalisation, and retention time over small molecule RLTs for the treatment of mCRPC.
A total of 242 patients have been treated with TLX591 across eight Phase I and Phase II trials9 including a previously published Phase II (open-label, single-arm) trial, which reported a 42.3 month OS in 17 patients with advanced mCRPC when TLX591 was delivered under a fractionated dosing regimen[10].
About ProstACT SELECT
The purpose of the ProstACT SELECT trial is to evaluate the utility of PSMA-PET imaging with Illuccix to select patients for TLX591 rADC therapy. The primary objectives are to determine whole body biodistribution and organ radiation dosimetry, and assess the safety and tolerability of TLX591 in patients with advanced mCRPC. Radiographic progression-free survival (rPFS) is a secondary study objective.
Previously reported data from the SELECT trial includes3:
Confirmation of biodistribution and safety profile with a low rate of off-target side effects.
Confirmation of internalisation and long retention, delivering a payload to the tumour, potentially maximising cell killing effect.
Lower rates of haematologic toxicity than prior, later-line studies of TLX591.