A phase 1b, open-label, multicenter study of xaluritamig in patients with biochemical recurrence of prostate cancer after definitive therapy.

TPS435 Background: Biochemical recurrence (BCR) develops in 20%–50% of patients with prostate cancer (PCa) after initial definitive treatment and is associated with an increased risk of distant metastasis and mortality (1). Despite significant advances, the most effective treatments for BCR often involve long-term toxicities, and most patients progress to metastatic disease (2). Thus, there is an unmet need for therapies with durable and deep responses without the long-term side effects and impaired health related quality of life associated with prolonged androgen deprivation therapy (ADT). In different tumor entities bispecific T-cell engagers (BITEs) may have better efficacy and safety in earlier stages of the disease (3). Xaluritamig, a BITE, simultaneously engages the six-transmembrane epithelial antigen of the prostate 1 (STEAP1) expressed on PCa cells and the CD3 complex on T cells, leading to T-cell mediated lysis of the STEAP1 expressing PCa cells. In an ongoing trial (NCT04221542), xaluritamig has demonstrated encouraging responses in patients with metastatic castration-resistant PCa. In the current study, safety, tolerability, and preliminary efficacy of xaluritamig are evaluated in patients with high-risk BCR. Methods: This Phase 1b, open-label, multicenter study aims to enroll approximately 40 patients diagnosed with high-risk BCR following definitive therapy. Eligibility criteria include histologically or cytologically confirmed prostate adenocarcinoma with BCR (defined as screening prostate specific antigen [PSA] ≥1 ng/mL after radical prostatectomy [RP], or ≥2 ng/mL after radiotherapy [XRT]); initial treatment with definitive therapy (either RP or XRT, or both); PSA doubling time of ≤12 months; and no evidence of metastasis in conventional imaging (PSMA-PET only positive imaging is allowed). The study includes a 28-day screening period, a six-cycle treatment period (each cycle lasting 28 days), a safety follow-up visit (30 days post-treatment), and a long-term follow-up period (up to 36 months). Xaluritamig will be administered as a short-term intravenous infusion over six cycles as monotherapy without ADT. Primary outcomes evaluate safety and tolerability through treatment-emergent and treatment-related adverse events. Secondary outcomes assess PSA response rates, time to progression, time to additional therapies, metastasis-free survival, treatment completion, and pharmacokinetics of xaluritamig. Statistical analysis for safety will include all enrolled patients receiving at least one dose of xaluritamig. Enrollment began in September 2024 and is ongoing. 1. Shore ND et al. Prostate Cancer Prostatic Dis. 2024 Jun;27(2):192-201. 2. Nguyen PL et al. Eur Urol. 2015;67(5):825-836. 3. Litzow MR et al. N Engl J Med. 2024;391(4):320-333. Clinical trial information: NCT06555796 .