Overview
This Phase 2a trial will evaluate the safety and efficacy of NK cell therapy combined with the hepatic artery infusion chemotherapy (HAIC) in patients with intermediate and/or locally advanced hepatocellular carcinoma (HCC). We hypothesized that 5-fluorouracil (FU) with immunomodulatory functions would relieve the immunosuppressive microenvironment from the myeloid-derived suppressor cells (MDSCs), thereby enhancing the anti-tumor activity of NK cells. Thus, the subsequent infusion of autologous NK cells (VAX-NK/HCC) following HAIC treatment may further improve the anti-tumor activity in patients with advanced HCC.
Description
Primary Objective I. To assess the objective response rate (ORR) of administering VAX-NK/HCC, autologous NK cells combined with HAIC in patients with locally advanced HCC.
Secondary Objectives I. To assess the efficacy of administering VAX-NK/HCC combined with HAIC. II. To assess the safety of administering VAX-NK/HCC combined with HAIC. III. To assess the immune responses of administering VAX-NK/HCC combined with HAIC.
OUTLINE: This is a Phase 2a study. Patients receive HAIC treatment every 4 week for up to 4 cycles followed by ex-vivo expanded autologous NK cell infusions. The NK cell treatment repeats every 4 weeks for up to 2 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients will be followed until the disease progression.
Eligibility
Inclusion Criteria:
- Subjects with intermediate and/or locally advanced HCC histologically confirmed by biopsy or by typical radiological findings.
- Subjects who were not suitable for or failed curative treatments such as surgical resection, local ablation therapy, transarterial chemoembolization (TACE), sorafenib, atezolizumab, bevacizumab, etc.
- Child-Pugh liver function class A or B.
- Subjects' ECOG performance status of 0 or 1.
- The presence of macrovascular invasion.
- Adequate liver, renal, and hematologic functions.
Exclusion Criteria:
- Subjects who received the immune cell-based therapy within 6 months before the screening visit.
- Subjects with a history of a malignancy other than HCC within the last 5 years, liver transplantation, and hypersensitivity to 5-FU or cisplatin.
- Subjects with extra-hepatic metastases.
- Subjects who have ongoing autoimmune disease.
- Female subjects who are pregnant or lactating or women of child-bearing potential but unable to take adequate contraception.
