133TiP - An open label pilot study to evaluate efficacy and safety of durvalumab with hepatic artery infusion chemotherapy (HAIC) in advanced hepatocellular (aHCC) patients with severe portal vein tumor thrombosis (PVTT) (Vp3 and/or Vp4): DurHope

Background

Portal vein tumor thrombus(PVTT) is very common in advanced HCC, which plays a major role in the poor prognosis and clinical staging of HCC. Emerging evidence shows that selected patients with PVTT will have better survival and ORR benefit from HAIC versus sorafenib. Oxaliplatin can be used as an inducer of immunogenic cell death(ICD) and as a modulator of the tumor immune microenvironment. Combination therapies composed of oxaliplatin and immune checkpoint inhibitors may open up novel avenues for the treatment of HCC. Therefore, durvalumab(an anti PD-L1 antibody) in combination with HAIC may have synergistic effect in aHCC patients with vp3/4 and improve the efficacy.

Trial design

This is a phase II, single arm study to evaluate the efficacy and safety of Durvalumab with HAIC in the Chinese advanced hepatocellular(aHCC) patients with Vp3 and/or Vp4 PVTT. Eligible patient Age ≥18 years and < 75 years; Child-Pugh score class A to B7; ECOG status of 0 or 1. Patients will administrated HAIC with modified FOLFOX6 regimens including (oxaliplatin 130 mg/m² infusion for 3 hours on day 1, leucovorin 200 mg/m² from hour 3 to 5 on day 1 and Fluorouracil 400 mg/m² in bolus, and then 2,400 mg/m² continuous infusion 46 hours; q3w; 4-6 cycles). Patients received durvalumab will begin on day 3±2 following the HAIC procedure. Durvalumab was given every 3 weeks during HAIC combination treatment (1120mg，Q3W) and every 4 weeks during durvalumab monotherapy(1500mg, Q4W) until disease progression or unacceptable toxicity. The primary endpoints will be 1 year OS rate; secondary endpoints include ORR and PFS by RECIST v1.1, safety; exploratory endpoint will be the relationship between the clinical efficacy and PD-L1 expression status.

Clinical trial identification

NCT04945720.

Legal entity responsible for the study

Sun Yat-sen University Cancer Center, Guangzhou, China.

Funding

AstraZeneca.

Disclosure

All authors have declared no conflicts of interest.