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First-in-human phase 1 study of an orally bioavailable vascular-disrupting agent DX1002 in patients with advanced solid tumors

Year: 2025

Type: article

Abstract: DX1002 is an oral vascular-disrupting agent and exhibits promising results in preclinical studies, leading to tumor vasculature destruction and xenografted tumor necrosis in various animal models. In the phase 1 trial, 17 patients with solid tumors receive DX1002 ranging from 50 to 1,100 mg. The maximum tolerated dose and recommended phase 2 dose of DX1002 are determined as 600 mg once daily. The most common treatment-related adverse events are nausea (23.5%), vomiting (17.6%), and fatigue (11.8%). All patients are evaluable for anti-tumor response, 12 of which achieve stable disease as best response. One patient with non-small cell lung cancer achieves a stable disease duration of 6.5 months. The median time to progression (TTP) is 2.70 months (95% confidence interval [CI], 0.90–4.60). Interestingly, reduced blood perfusion is observed by contrast-enhanced ultrasound in a patient with colon cancer. In conclusion, DX1002 is well tolerated and exhibits preliminary anti-tumor efficacy in patients with solid tumors. This study was registered at chictr.org.cn (ChiCTR2400080298). • DX1002 is an orally bioavailable vascular-disrupting agent • DX1002 leads to tumor vasculature destruction and necrosis in various animal models • DX1002 shows manageable safety and preliminary anti-tumor efficacy in phase 1 study Wei et al. present the preclinical results and phase 1 dose-escalation study of DX1002, an orally bioavailable vascular-disrupting agent. DX1002 can lead to tumor vasculature destruction and xenografted tumor necrosis in various animal models and shows manageable safety and preliminary anti-tumor efficacy in this phase 1 study.

Source: Cell Reports Medicine

DOI: 10.1016/j.xcrm.2025.101969