First-in-human results of terbium-161[ 161 Tb]Tb-PSMA-I&T radioligand treatment in patients with metastatic castration-resistant prostate cancer (VIOLET): A single-centre, single-arm, phase I/II study.

• DOI: 10.1200/jco.2025.43.16_suppl.5010
• Publication Date: 2025-05-28T15:54:41Z
• Authors: James Patrick Buteau; Louise Kathleen K...; Price Jackson; Lachlan McIntosh; Ramin Alipour; Timothy J. Akhurst; Michal Eifer; Brittany Emmerson; Mohammad B. Haskali; Kerry Jewell; Raghava Kashyap; Grace Kong; Declan Murphy; Aravind S. Ravi K...; Javad Saghebi; Shahneen Sandhu; Ben Tran; Jing Xie; Arun Azad; Michael S. Hofman
• Keywords: Radioligand; Terbium

5010 Background: Terbium-161 ( 161 Tb) is a novel radionuclide emitting beta-radiation comparable to lutetium-177 177 Lu), with additional higher-energy, ultra-short path-length Auger electrons which may better target micrometastases. Tb has superior in-vitro and in-vivo efficacy in comparison Lu. We aim evaluate the safety effectiveness of [ Tb]Tb-PSMA-I&T patients metastatic castration-resistant prostate cancer (mCRPC). Methods: Eligible this investigator-initiated, single-centre, single-arm, phase I/II trial had progressive mCRPC previously treated taxane chemotherapy (unless medically unsuitable) an androgen receptor pathway inhibitor, PSMA-positive disease on PSMA PET/CT (SUVmax ≥20), no sites discordance FDG PET/CT, adequate bone marrow, hepatic renal function, ECOG performance status ≤2. The dose-escalation followed 3+3 design establish three prespecified administered radioactivities (4.4, 5.5, 7.4 GBq). Up six cycles were intravenously every weeks, each subsequent radioactivity per cycle reduced by 0.4 GBq. co-primary objectives maximum tolerated dose (MTD) profile (CTCAE v5.0) Tb]Tb-PSMA-I&T. Key secondary for interim analysis PSA ≥50% ≥90% response rates (PSA50-RR PSA90-RR), radiographic progression-free survival (PSA-PFS rPFS). Results: Between October 14, 2022 February 15, 2024, 30 eligible enrolled. Median (IQR) age 69.0 years (66.0-74.8), median baseline 26.9 ng/mL (10.1-70.0), SUVmean 8.2 (7.4-10.8) 20 (67%) received prior docetaxel. There dose-limiting toxicities. MTD recommended 2 was treatment-related deaths few grade 3 or higher adverse events, included pain flare lymphopenia only. remaining AEs are summarised table. PSA50-RR PSA90-RR occurred 21 (70% [95%CI 51-85]) 12 (40% 23-59]). PSA-PFS rPFS 9.0 months (95%CI 5.7-15.1) 11.1 6.6-11.7) follow-up 11.2 11.0 months, respectively. Conclusions: displayed highly encouraging Grade 4 events. An cohort assess planned. Clinical information: NCT05521412 . Main Adverse event 1 Total Lymphocyte count decreased 8 10 0 19 (63%) Pain (13%) Anemia 16 Neutrophil 6 (20%) Fatigue 13 (43%) Dry mouth (70%) Nausea 7 (23%) Platelet Any 14 29 (97%)