A single-arm IIT study of HA131 (hepatic arterial infusion) in combination with systemic therapy (XELOX with or without bevacizumab) as first-Line treatment in gastrointestinal cancer with liver metastases.

e15546 Background: Hepatic arterial infusion chemotherapy (HAIC) combined with systemic therapy could be more effective in controlling the progression of liver lesions. Paclitaxel Cationic Liposomes for injection (HA131) exerts a dual anti-tumor action mechanism through the cytotoxic effect and cationic liposome targeting to negatively charged tumor neovascular endothelial cells, blocking the supply of nutrients, and inducing the apoptosis of tumor cells. Here we report the preliminary results of a single-arm IIT study. Methods: This single-arm study enrolled gastrointestinal liver metastases were enrolled. Based on the one accelerated titration followed by a 3+3 design with 5 planned HA131 dose levels, the initial dose of HA131 was 11 mg/m 2 followed by 22, 33, 44, and 55 mg/m 2 via hepatic arterial infusion at day15 every 3 weeks for 6-8 cycles. The XELOX regimen with or without Bevacizumab at day1 intravenously. The primary endpoints were safety and tolerability; major secondary endpoints were overall response rate (ORR) and disease control rate (DCR) assessed by RECIST v1.1/mRECIST. Results: As of January 20, 2025, 18 patients with liver metastasis were enrolled with one being gastric cancer, one being pancreatic cancer, and sixteen being colorectal cancer. During the dose-escalation phase, four dose levels (11-44 mg/m 2 ) have been completed with no dose-limiting toxicities observed, with 1, 3, 3, 3 patients receiving 11 mg/m 2 , 22 mg/m 2 , 33 mg/m 2 and 44 mg/m 2 , respectively, and 55 mg/m 2 is under recruiting. One dose expansion at HA131 44 mg/m 2 enrolled eight patients. All patients experienced treatment-related adverse events (TRAEs) of any grade, of which 12 (66.7%) were ≥ grade 3 TRAEs of HA131 plus systemic therapy. The most common TRAEs included decreased platelet count (88.9%) and fever (83.3%), mainly grade 1-2 and most of them have been resolved within 7-10 days. There were no AEs leading to death. Of the 15 patients with colorectal cancer liver metastasis evaluable for response, the ORR was 86.7% (95% CI: 59.5%-98.3%) with 1 complete response (CR) plus 12 partial responses (PRs), and the DCR was 100% (95% CI: 78.2%-100%) as per RECIST v1.1. The ORR assessed by mRECIST was 93.3% (95% CI: 68.0%-99.8%) with 3 CRs and 11 PRs. Conclusions: HA131 hepatic arterial infusion chemotherapy in combination with systemic chemotherapy shows manageable safety profile and encouraging efficacy, which warrants further study in combination with systemic therapy in patients with gastrointestinal cancer with liver metastases. Clinical trial information: ChiCTR2300069012 .