A phase II clinical trial of ivonescimab (VEGFxPD-1 bispecific antibody) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Abstract

TPS5138 Background: Patients with mCRPC achieve limited responses with single-agent immune checkpoint therapies (ICTs), due to tumor microenvironments (TME) characterized by few intratumoral effector T cells and high prevalence of suppressive myeloid cell populations, cytokines, and signaling pathways. In murine models of mCRPC, tyrosine kinase inhibitors (TKIs, i.e. against vascular endothelial growth factor [VEGF] receptor 2, MET, and AXL, among others) inhibited tumor infiltrating myeloid-derived suppressor cells and enhanced responses to ICTs (Lu X et al., Nature 2017). Consistent with this, a phase III clinical trial combining TKI and anti-PD-(L)1 demonstrated improved clinical outcomes in a subset of patients with mCRPC (Agarwal N et al., Lancet Oncol 2025). Ivonescimab is a first-in-class bispecific antibody simultaneously targeting PD-1 and VEGF-A that has demonstrated clinical activity across multiple tumor types. We hypothesized that ivonescimab will induce anti-tumor responses in a subset of patients with mCRPC. Methods: This is an open-label, single-center phase II clinical trial in patients with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell histology. The primary endpoint of the study is objective response rate per Prostate Cancer Working Group 3 (PCWG3) criteria, and secondary endpoints include duration of response (DOR), disease control rate (DCR) greater than 6 months), radiographic progression free survival (rPFS), PSA 50 responses (defined as confirmed > 50% decline in PSA from baseline) and incidence, severity, and duration of adverse events. Tumor biopsies are collected at baseline and prior to C2D1 for evaluation of biomarkers of response and resistance to therapy. The study is being conducted using a Bayesian optimal phase 2 (BOP2) design. A total of up to 24 patients will be enrolled on study. The study is currently open and enrolling (NCT06567314). Clinical trial information: NCT06567314 .