Abstract 727: Association of baseline tumor and peripheral biomarker features with efficacy in metastatic castration-resistant prostate cancer patients treated with xaluritamig

作者：Benjamin E. Decato, Zhao Yang, Isabelita Vengco, Katherine L. Paweletz, Amrita Pati, Anita J Reddy, Tara J. O’Donohue, Sheryl Treichel, Kristen M. Smith · 发表于：Cancer Research · 年份：2025 · DOI：10.1158/1538-7445.am2025-727 · 被引用次数：2 · 研究领域：Prostate Cancer Treatment and Research、Hepatocellular Carcinoma Treatment and Prognosis、Cancer, Hypoxia, and Metabolism

Abstract Xaluritamig, a novel STEAP1 x CD3 XmAb® 2+1 T-cell engager, is showing initial safety and efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report on the association of baseline tumor and peripheral biomarker characteristics with efficacy in the first-in-human dose exploration trial. We examined STEAP1 target expression by immunohistochemistry in fresh and archival tumor biopsies, peripheral immune populations by multiparameter flow cytometry, and tumor somatic mutations via circulating tumor DNA (ctDNA) in plasma. STEAP1 was broadly expressed in mCRPC subjects with greater than 95% of tumor biopsies containing at least 1% STEAP1-positive tumor cells. STEAP1 expression was similar at various metastatic sites examined in the patient cohort and was not impacted by the number or types of prior therapies. Additionally, STEAP1 expression levels were not correlated with PSMA expression. Neither STEAP1 IHC intensity nor the percentage of STEAP1-positive tumor cells correlated with response to xaluritamig. Baseline peripheral immune cell populations and blood chemistry features may potentially associate with response. Patients who achieved a PSA50 response had lower neutrophil counts, neutrophil-to-lymphocyte ratio, and C-reactive protein than non-responding patients. The association between xaluritamig response and baseline tumor T cell infiltration is being assessed. Baseline somatic tumor mutations were determined by analysis of c...