Melbourne (Australia) | 31 May 2024

  • TLX591 is an investigational anti-PSMA[1] radio-antibody-drug conjugate (rADC) therapy being developed for the treatment of mCRPC, differentiated by a short two-week dosing regimen.
  • Reported median radiographic progression-free survival (rPFS) is 8.8 months.
  • Builds on prior data from the ProstACT SELECT[2] trial, demonstrating favourable safety profile and biodistribution[3].

Telix today announces 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). 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 study[3].

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.

A total of 242 patients have been treated with TLX591 across eight Phase I and Phase II trials[9] 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].

TLX591 has not received a marketing authorisation in any jurisdiction.

To read the full ASX release click here

[1] Prostate-specific membrane antigen.

[2] ProstACT SELECT ID: NCT04786847.

[3] Telix ASX disclosure 19 October 2023.

[4] Imaging of prostate-specific membrane antigen with positron emission tomography.

[5] The study recruited 30 patients, with 5 patients completing low-dose dosimetry. Two patients did not complete a second dose and therefore were excluded from the rPFS calculation.

[6] Hofman et al. Lancet Oncol 2018; Violet et al. Journal of Nuc Med 2019; Calais et al. Journal of Nuc Med 2021.

[7] ProstACT GLOBAL ID: NCT04876651.

[8] 152 mCi cumulative radiation exposure with TLX591 compared with up to 1200 mCi with current approved RLT, based on prescribing information.

[9] Bander et al. J Clin Oncol. 2005; Tagawa et al. Clin Cancer Res. 2013; Tagawa et al. Cancer. 2019; Batra et al. Urol Oncol. 2020; Niaz et al. Oncologist. 2020. 

[10] Tagawa et al. Cancer. 2019.