XALience: A phase 3, open-label, multicenter, randomized study of xaluritamig plus abiraterone vs investigator’s choice in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer.

Abstract

TPS5144 Background: In the first-in-human (FIH) study, xaluritamig, a T-cell engager directed at six-transmembrane epithelial antigen of the prostate 1 (STEAP1), demonstrated potent antitumor activity with a manageable safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC). 1,2 Preliminary data from this FIH study of xaluritamig in combination with abiraterone in chemotherapy-naïve patients with mCRPC 3 supports the initiation of a phase 3 study of xaluritamig plus abiraterone with the aim of improving survival in this population. Methods: XALience is a randomized, multicenter, open-label, phase 3 study (NCT07213674) of xaluritamig plus abiraterone vs investigator’s choice in patients with chemotherapy-naïve mCRPC. Approximately 750 eligible patients ≥18 years old with histologically confirmed chemotherapy-naïve mCRPC; evidence of disease progression on prior enzalutamide, apalutamide, or darolutamide; ECOG PS of 0-1; and adequate organ function and who may have previously received ≤6 cycles of docetaxel in the metastatic hormone-sensitive prostate cancer (mHSPC) setting will be randomized 1:1 to receive xaluritamig plus abiraterone or investigator’s choice of docetaxel, cabazitaxel, or abiraterone. Patients will be stratified by prior docetaxel exposure in mHSPC, presence of liver metastases, prior treatment with prostate-specific membrane antigen radioligand therapy, and planned intention-to-treat with investigator’s choice. This study consists of a 28-day screening period, treatment until radiographic progression based on Prostate Cancer Working Group 3 (PCWG3) guidelines, a safety follow-up period, and a long-term follow-up period. To mitigate the risk of cytokine release syndrome, xaluritamig will be initiated at weekly step-up dosing over four doses up to the target dose during cycle 1 followed by target dose administration every 2 weeks from cycle 2 day 1 onwards. The primary endpoint is overall survival, which will be analyzed using a stratified log-rank test at a one-sided 2.5% significance level. Key secondary endpoint is investigator-assessed radiographic progression-free survival per PCWG3. Other secondary endpoints include radiographic and prostate-specific antigen response, safety, tolerability, health-related quality of life, patient-reported outcomes, pharmacokinetics, and immunogenicity. Enrollment is ongoing and 20 patients have been enrolled as of January 19, 2026. References: Kelly WK, Danila DC, Lin CC, et al. Cancer Discov. 2024;14:76-89. Kelly WK, Appleman L, Lin C-C, et al. Ann Oncol . 2024;35: S963-S964. Data on file, Amgen; 2025. Clinical trial information: NCT07213674 .