New Xaluritamig (AMG 509) Monotherapy Phase 1 Trial for mCRPC

Xaluritamig (AMG 509) represents a promising new immunotherapy option for men with metastatic castration-resistant prostate cancer, or mCRPC, through this  new Phase 1 trial. The study aims to evaluate the safety profile of xaluritamig administered as monotherapy (plus ADT, as usual) at a specific proposed regimen in adult male participants whose cancer has progressed despite prior treatments. Unlike previous xaluritamig trials that have explored combinations or different settings, this one focuses solely on monotherapy in heavily pretreated patients, filling a gap in targeted T-cell engager therapies for late-stage disease.

The trial targets men aged 18 and older with confirmed mCRPC who have progressed on at least one androgen receptor pathway inhibitor such as enzalutamide or abiraterone, and exactly one taxane therapy in the mCRPC setting, like docetaxel or cabazitaxel. Prior docetaxel in the earlier metastatic hormone-sensitive phase is allowed if followed by one taxane in mCRPC.

Xaluritamig, also known as AMG 509, works as a STEAP1 x CD3 XmAb 2+1 bispecific T-cell engager that binds to STEAP1, a protein overexpressed on prostate cancer cells, and recruits T-cells to form an immune synapse for targeted tumor cell lysis. This mechanism showed encouraging results in earlier first-in-human dose exploration, with 49% achieving PSA50 responses and 24% objective responses by RECIST criteria across cohorts, improving to 59% PSA50 and 41% at higher doses like 0.75 mg or above, even in taxane-pretreated patients. These prior data validate STEAP1 as a viable target and underscore xaluritamig’s potential where standard options falter.

As a novel approach distinct from AR inhibitors or chemotherapies, this monotherapy trial could pave the way for broader Phase 3 evaluation in post-taxane mCRPC, offering hope for improved outcomes in this challenging population.

Clinical trial.