On October 18, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported positive preliminary results from the Phase I ProstACT SELECT study of its rADC therapy candidate TLX591 (Lutetium (177Lu) rosopatamab tetraxetan) for prostate-specific membrane antigen (PSMA) positive metastatic castration-resistant prostate cancer (mCRPC) (Press release, Telix Pharmaceuticals, OCT 18, 2023, View Source [SID1234636120]).
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The purpose of the SELECT study (ClinicalTrials.gov ID: NCT04786847) was to evaluate the utility of PSMA imaging to select patients for rADC-based PSMA therapy and to confirm the biodistribution of the rADC investigational therapy. The primary clinical objective was to determine whole body distribution and organ radiation and assess the safety and tolerability of TLX591, when administered in combination with SoC in second-line mCRPC.
The evaluable population was 28 patients (of a total 30 enrolled in the study). Patients received two (2) single intravenous (IV) infusions of TLX591, fourteen (14) days apart. Cohort 1 (5 patients) received a 27mCi dose followed by a 76 mCi dose for accuracy of biodistribution determination. Cohort 2 (23 patients) received two 76mCi doses.
The study achieved its primary objectives, confirming the safety and tolerability profile of TLX591 administered in two cycles,14 days apart (total cumulative dose 152mCi). The results reinforce the clinical utility of the short, fractionated dosing regimen.
Key results and observations
Dosimetry and biodistribution
Consistent lesion delineation between TLX591 and 68Ga-PSMA-11 imaging, within the detection sensitivity and resolution limits of SPECT[4]
Excellent uptake and retention in tumour and metastases up to 14 days post injection
Radiation exposure to key organs is well within prescribed safety limits
The highest absorbed dose was in the liver (clearance organ), with minimal uptake in exocrine (salivary) glands
Long retention period is evidence of internalisation and ability to efficiently deliver payload to tumour
Hematologic profile and adverse events
Grade 3 thrombocytopenia (25%) and neutropenia (38%) events in line with profile expected for this class of therapy. Similarly for Grade 4 hematologic events – thrombocytopenia (25%) and neutropenia (4%)
Serious adverse events (SAEs) observed were generally lower than in earlier studies conducted at the same dose level, reflective of the SELECT study being conducted in a healthier patient population
Hematologic events were transient and reversible
Four patients (17%) received intervention in the form of platelets, growth factors or both
All treatment related non-hematologic events were Grade 1 or Grade 2 and generally mild
Preliminary anti-tumour activity
64% of patients (baseline PSA and full dose) had a PSA reduction, with 27% demonstrating a 30% reduction and 18% demonstrating a 50% reduction. PSA and rPFS monitoring is ongoing
Scott T. Tagawa, MD, Professor of Medicine and Urology in New York said, "Preliminary results from the ProstACT SELECT study build on prior studies of TLX591 and underline the potential advantages of an antibody-based approach. Latest data provides further evidence of the long retention and internalisation of TLX591 in the tumour (and metastases), which may maximise the cell-killing effect of the 177Lu radioisotope at the site of the tumour."
Nat Lenzo, MD, GenesisCare Group Clinical Director Theranostics and top recruiter onto the ProstACT SELECT study commented, "It is really exciting to see development of this next-generation PSMA-targeting radiotherapeutic progressing. This study confirms the suitability of the short, simple treatment duration with two doses administered two weeks apart which is attractive to physicians and patients. The safety and tolerability data also demonstrates the potential for this therapy to reduce undesirable side effects, while delivering a hematologic toxicity profile that is both tolerable and manageable."
Colin Hayward, Telix Chief Medical Officer, added, "TLX591 is being designed to integrate with current standard of care, demonstrative of Telix’s continued innovation in prostate cancer treatment. The SELECT study provides further validation of the potential of TLX591, a first-in-class rADC therapy and the use of PSMA imaging with small molecules to select patients for antibody-based PSMA therapy."
Investigation of TLX591 is continuing in the Phase III ProstACT GLOBAL study (ClinicalTrials.gov ID NCT04876651), open for enrolment in Australia and expected to commence in the United States in 2024.