Safety, tolerability, and dosimetry of 177Lu-TLX591 with best standard of care in patients with PSMA-expressing metastatic castration-resistant prostate cancer (ProstAct-SELECT).

TPS253 Background: Prostate-specific membrane antigen (PSMA) has proven to be an ideal therapeutic target in prostate cancer (PC) as it is highly expressed by malignant prostate cells. Based on previous clinical evidence of its favorable safety profile and specificity for PC tumors, 177 Lu-DOTA-HuJ591-CHO (hereafter referred to as 177 Lu-TLX591) may be a potential radioimmunotherapy for the treatment of PC. ProstACT-SELECT (NCT04786847) is a phase 1 study designed to evaluate the safety, tolerability, biodistribution and dosimetry of 177 Lu-TLX591 administered with standard of care (SoC) for patients with PSMA-expressing, metastatic castration-resistant prostate cancer progressing despite prior treatment with a novel androgen axis drug. We previously reported positive interim results, and primary analysis of safety and dosimetry data is currently underway and expected to be available in mid-October 2023. Methods: Approximately 30 participants were to be enrolled in 2 cohorts. Cohort 1: 5 patients received a single (27 mCi) intravenous infusion of 177 Lu-TLX591. SPECT images and pharmacokinetic blood samples will be acquired at several time points until Day 13 after dosing. Dosimetry analysis and qualitative comparison of biodistribution of tracer level of 177 Lu-TLX591, as demonstrated by SPECT, with 68 Ga-PSMA-11 on PET imaging were performed to ensure equivalent (or improved) radiopharmaceutical tumour targeting. Patients were to receive a second administration of 177 Lu-TLX591, at a full therapeutic dose of 76 mCi, 14 days following the initial dose after safety confirmed by independent review board. SoC was to continue according to standard practice. Cohort 2: Subsequent patients were to receive 2 administrations of 76 mCi 177 Lu-TLX591, with SPECT dosimetry and pharmacokinetics as in cohort 1. The primary endpoints include the absorbed radiation dose of administered 177 Lu-TLX591 to kidneys, liver, lungs, spleen, bone/red marrow, and salivary glands; tumour-to-healthy tissue ratios and residence times; and type, frequency, and severity of TEAEs. Clinical trial information: NCT04786847 .