HA131 (hepatic arterial infusion) in combination with systemic therapy (XELOX with or without bevacizumab) as first-line treatment in gastrointestinal cancer with liver metastases: A prospective study.

e15531 Background: Hepatic arterial infusion (HAI) chemotherapy combined with systemic therapy may better control the progression of liver lesions. Up to the present, there have been no relevant reports on the application of liposomal paclitaxel formulation in combined systemic treatment of gastrointestinal cancer with liver metastasis. Here, we assessed the safety and primary efficacy of HA131 (a novel cationic liposomal paclitaxel formulation) administered via HAI plus systemic chemotherapy for gastrointestinal cancer with liver metastases. Methods: This open-label dose escalation and dose expansion phase I clinical trial was conducted at two centers in China. Based on accelerated titration followed by a 3+3 design with five planned HA131 dose levels, the initial dose of HA131 was 11 mg/m 2 followed by 22, 33, 44, and 55 mg/m 2 administered on Day 15 every 3 weeks for about 6–8 cycles. XELOX (±bevacizumab) administration was repeated every 3 weeks accordingly. The primary endpoint of the study was safety; secondary endpoints included pharmacokinetics (PK) charactertics, overall response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), which were assessed using the RECIST v1.1/mRECIST criteria. Results: Twenty-three patients were enrolled between March 13, 2023, and December 12, 2025. Evaluation of five HA131 dose levels revealed no dose-limiting toxicities. All patients experienced treatment-emergent adverse events (TEAEs), with 87.0% experiencing TEAEs of grade 3 or higher. The most common HA131-related TEAEs were thrombocytopenia, elevated procalcitonin, lymphopenia, neutrophilia, and leukocytosis. No drug-related fatal TEAEs have been reported to date. Among the 20 evaluable patients, ORR was 85.0% per RECIST and 90.0% per mRECIST; in patients with colorectal liver metastases (n = 18), ORR was 88.9% and 94.4% accordingly; both with a DCR of 100.0%. All patients exhibited tumor shrinkage following treatment. After a median follow-up of 13.3 months, the median PFS has not been reached (6 patients had disease progression). The estimated 18-month PFS rate was 65.7%. In addition, nonlinear pharmacokinetic properties were observed. Conclusions: This regimen demonstrated manageable safety and notably primary efficacy, warranting further exploration in patients with gastrointestinal cancer and liver metastases. Clinical trial information: ChiCTR2300069012.