What question did this study set out to answer?

To evaluate the efficacy and safety of durvalumab plus HAIC-FOLFOX in hepatocellular carcinoma patients with Vp4 portal vein tumor thrombus.

May 20, 2026Open Access

Durvalumab plus HAIC-FOLFOX followed by maintenance durvalumab for hepatocellular carcinoma with major portal invasion: phase 2 DurHope study

Key Points

To evaluate the efficacy and safety of durvalumab plus HAIC-FOLFOX in hepatocellular carcinoma patients with Vp4 portal vein tumor thrombus.
Single-arm phase 2 study with 30 patients
Participants received durvalumab and HAIC-FOLFOX as first-line treatment
Endpoints included overall survival and biomolecular analyses.
1-year overall survival rate was 63.3%, with median overall survival of 13.9 months (95% CI, 10.7–NR)
Exploratory RNA sequencing identified chemotherapy resistance signatures in nonresponders
Increased T-cell subsets and cytotoxic gene expression were noted in responders.

Abstract

Hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT) have a poor prognosis and are underrepresented in global clinical trials. We conducted a single-arm phase 2 study (DurHope) enrolling 30 patients with Vp3/4 PVTT receiving durvalumab plus hepatic arterial infusion therapy (HAIC) of FOLFOX regimen (fluorouracil, leucovorin, and oxaliplatin) as first-line treatment. Primary endpoint was 1-year overall survival (OS) rate, and secondary endpoints included progression-free survival, objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, and safety. The pre-specified study endpoints were achieved, the 1-year OS rate was 63.3%, with a median OS of 13.9 months (95% CI, 10.7–not reached NR) at the final analysis. In exploratory, post hoc biomolecular analyses, tumor single-nucleus RNA sequencing revealed chemotherapy resistance and immune escape signatures in nonresponders, including a MECOM+ malignant subcluster. Responders showed increased immune infiltration and stronger immune-tumor interactions. Peripheral blood dynamic single-cell RNA sequencing demonstrated expanded T-cell subsets and increased expression of cytotoxic-related genes after treatment, which was more pronounced in responders. This was accompanied by decreased nonclassical monocyte frequency and attenuated anti-inflammatory phenotype in responders. Findings were validated by immunohistochemistry and in vivo models. These data suggested the promising efficacy and generally tolerable toxicity of Durvalumab plus HAIC-FOLFOX in patients with Vp4 PVTT and provided candidate biomarkers. ClinicalTrials.gov number: NCT04945720. Patients with hepatocellular carcinoma (HCC) with Vp4 portal vein tumour thrombus (PVTT) have poor prognosis and are underrepresented in clinical trials. Here, the authors report a phase 2 clinical trial evaluating first-line durvalumab (anti-PD-L1) plus HAIC-FOLFOX (hepatic arterial infusion chemotherapy) in patients with HCC with Vp4 PVTT, along with biomolecular and preclinical analysis.

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Cite This Study

YI et al. (Mon,) studied this question.

synapsesocial.com/papers/6a0d4ec0f03e14405aa99ea8 https://doi.org/https://doi.org/10.1038/s41467-026-73131-y

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