Phase 2 study of durvalumab plus HAIC-FOLFOX and durvalumab maintenance for hepatocellular carcinoma with major portal invasion

Hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT) have a poor prognosis and are underrepresented in global clinical trials. The phase 2 DurHope study at Sun Yat-sen University Cancer Center (Guangzhou, China) evaluated durvalumab plus hepatic arterial infusion (HAIC) of FOLFOX followed by durvalumab maintenance as first-line treatment for HCC with Vp3/4 PVTT. Primary endpoint was 1-year overall survival (OS) rate; secondary endpoints were progression-free survival, objective response rate, and safety. The study enrolled 30 patients. The pre-specified endpoints were met; the 1-year OS rate was 63.3%, with a median OS of 13.9 months (95% CI 10.7-NR). Exploratory analyses revealed chemotherapy resistance and immune escape signatures in nonresponders, including a MECOM+ malignant subcluster. Responders showed increased immune infiltration and stronger immune-tumor interactions. Expanded T-cell subsets and increased expression of cytotoxicity-related genes after treatment were more pronounced in responders. The authors conclude that these data suggest promising efficacy of first-line durvalumab plus HAIC-FOLFOX followed by durvalumab maintenance in HCC patients with Vp3/4 PVTT, and provided candidate biomarkers.