A phase 1b, open-label, multicenter study of xaluritamig in patients with newly diagnosed localized intermediate- or high-risk prostate cancer in the neoadjuvant setting.

TPS434 Background: There are currently no standard neoadjuvant treatments for patients with localized prostate cancer despite improved outcomes with neoadjuvant therapy in multiple other solid tumors. Xaluritamig is a bispecific T-cell engager (TCE) that simultaneously engages the six-transmembrane epithelial antigen of the prostate 1 (STEAP1) expressed on prostate cancer cells and the CD3 complex on T cells, thereby leading to T-cell mediated lysis of the STEAP1 expressing prostate cancer cells. In an ongoing trial (NCT04221542), xaluritamig has demonstrated deep, early, and durable responses in patients with metastatic castration-resistant prostate cancer. Notably, TCEs as a class of therapy have demonstrated the potential to have even greater efficacy and safety when used in earlier stages of disease where the overall disease burden is less and immune fitness is generally better. These data suggest that xaluritamig may be safely administered in the neoadjuvant setting and lead to pathologic responses with subsequent improvement in disease control and long-term clinical outcomes. In the current study, safety and feasibility as well as preliminary efficacy of neoadjuvant xaluritamig are being evaluated in patients with newly diagnosed localized intermediate or high-risk prostate cancer. Methods: This Phase 1b, open-label, multicenter study plans to enroll approximately 30 patients diagnosed with localized intermediate or high-risk prostate cancer and are planned for radical prostatectomy. Eligibility criteria includes histologically or cytologically confirmed prostate adenocarcinoma with Gleason Score ≥4+3 and an initial prostate specific antigen (PSA) of ≥10 ng/ml, no evidence of metastasis outside of the surgical resection field (PSMA-PET positive locoregional lymph nodes or less or equal 5 local lymph nodes on MRI can be enrolled), or use of any prior therapy for prostate cancer. The study includes a 28-day screening period, a two-cycle neoadjuvant treatment period (each cycle lasting 28 days), a safety follow-up visit (up to 42 days) after surgery, and a long-term follow-up period (up to 42 months). The last dose of xaluritamig will be administered about 14 to 28 days prior to undergoing radical prostatectomy. Primary outcomes will evaluate xaluritamig through treatment-emergent and treatment-related adverse events, and feasibility of radical prostatectomy. Secondary outcomes will assess PSA response, imaging-based response on multiparametric magnetic resonance imaging (mpMRI) prior to prostatectomy, pathologic response and the pharmacokinetics of xaluritamig. The study is open for enrollment as of October 2024. Clinical trial information: NCT06613100 .