Phase 2 Trial for The Combo Fasudil Hydrochloride Plus PD-1 Immune Checkpoint Blockade

A clinical trial at Zhongda Hospital in China is testing a combination of fasudil hydrochloride, a Rho-associated kinase (ROCK) inhibitor, with PD-1 immune checkpoint blockade in patients with advanced metastatic castration-resistant prostate cancer (mCRPC). This Phase II open-label trial enrolls patients aged 18 to 85 years who have progressed after at least one docetaxel-containing chemotherapy regimen and one standard novel endocrine therapy.

Fasudil’s role in the trial is built on its capacity to target the tumor microenvironment, which in mCRPC is highly immunosuppressive and characterized by abnormal vasculature and hypoxia that impede effective T-cell infiltration. As a ROCK inhibitor, fasudil normalizes dysfunctional tumor blood vessels by modulating pericyte contractility and endothelial barrier function, leading to enhanced blood flow, oxygenation, and expression of adhesion molecules critical for immune cell trafficking. This vascular normalization alleviates hypoxia-induced immunosuppression and facilitates the infiltration of CD8+ cytotoxic T lymphocytes into tumors. Additionally, fasudil reprograms tumor-associated macrophages from the pro-tumoral M2 phenotype to the pro-inflammatory M1 phenotype, enhancing anti-tumor immunity. These effects synergize with PD-1 blockade, which restores exhausted T cells’ ability to recognize and kill tumor cells by inhibiting the interaction between PD-1 receptors on T cells and PD-L1 expressed by tumor and immune cells.

The immunotherapy agent used is likely triprilizumab or a similar PD-1 monoclonal antibody developed in China, part of a growing class of checkpoint inhibitors designed to unleash T-cell mediated immune responses against prostate cancer cells. Previous experience with PD-1 inhibitors as monotherapy in late-stage mCRPC has shown limited efficacy, primarily due to a hostile tumor immune microenvironment and poor immune cell infiltration. The addition of fasudil aims to overcome these barriers by modifying the tumor stroma and enhancing immune access, potentially converting immunologically “cold” tumors into “hot” ones responsive to immunotherapy.

Clinical trial.