Clinical trial NCT05040438: Natural Killer (NK) Cell Therapy in Locally Advanced HCC
Official title: A Phase 2a Study Using Natural Killer (NK) Cell Therapy Combined With Hepatic Artery Infusion Chemotherapy (HAIC) in Patients With Locally Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Locally Advanced Hepatocellular Carcinoma
Lead sponsor: Vaxcell Bio, Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-09-10
Enrollment: 17
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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 criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) of administering VAX-NK/HCC combined with HAIC
timeFrame: average 6 months
Secondary outcomes:
measure: Disease control rate (DCR) of administering VAX-NK/HCC combined with HAIC
timeFrame: average 6 months
measure: Time to progression (TTP) of administering VAX-NK/HCC combined with HAIC
timeFrame: average 6 months
measure: Overall survival (OS) of administering VAX-NK/HCC combined with HAIC
timeFrame: average 12 months
measure: Quality of Life of administering VAX-NK/HCC combined with HAIC
timeFrame: average 6 months
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs) of administering VAX-NK/HCC combined with HAIC
timeFrame: average 6 months
measure: The proportions of T and NK cells
timeFrame: average 6 months
measure: The lymphocyte/monocyte ratio (LMR)
timeFrame: average 6 months
measure: The NK cell cytotoxicity
timeFrame: average 6 months
measure: The serum cytokine levels
timeFrame: average 6 months
Other outcomes:
Locations:
city: Hwasun
country: Korea, Republic of
facility: Seon-Ah Ha
state: Jeollanam-do
Study officials:
affiliation: VaxCell Biotherapeutics Co., Ltd.
name: Seon-Ah Ha, Ph.D.
role: STUDY_DIRECTOR
References: