Natural Killer (NK) Cell Therapy in Locally Advanced HCC

Locally Advanced Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05040438
• Other study ID #: Vax-NK/HCC-201
• Status: Recruiting
• Phase: Phase 2
• Start date: October 15, 2019
• Est. completion date: May 31, 2024

Study information

• Verified date: May 2023
• Source: Vaxcell Bio, Co., Ltd.
• Contact: Seon-Ah Ha, Ph.D.
• Phone: +82-61-375-8863
• Email: seonah387[@]vaxcell-bio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: May 31, 2024
• Est. primary completion date: September 18, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Locally Advanced Hepatocellular Carcinoma

Intervention

Biological:
• Vax-NK/HCC
autologous NK cells expanded ex vivo.

Locations

Country	Name	City	State
Korea, Republic of	Seon-Ah Ha	Hwasun	Jeollanam-do

Sponsors (1)

Lead Sponsor	Collaborator
Vaxcell Bio, Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) of administering VAX-NK/HCC combined with HAIC	ORR will be measured as the proportion of patients with a best overall response of complete response (CR) and partial response (PR) of administering VAX-NK/HCC combined with HAIC.	average 6 months
Secondary	Disease control rate (DCR) of administering VAX-NK/HCC combined with HAIC	ORR will be measured as the proportion of patients with a best overall response of complete response (CR), partial response (PR), and stable disease (SD) of administering VAX-NK/HCC combined with HAIC.	average 6 months
Secondary	Time to progression (TTP) of administering VAX-NK/HCC combined with HAIC	TTP will be measured by time to progression, defined as time from enrollment to disease progression.	average 6 months
Secondary	Overall survival (OS) of administering VAX-NK/HCC combined with HAIC	OS will be measured as time from enrollment to death due to any cause.	average 12 months
Secondary	Quality of Life of administering VAX-NK/HCC combined with HAIC	The assessment will be performed using the Korean versions of European Organization for Research and Treatment of Cancer (EORTC) Questionnaire 30 (QLQ-C30) consisting of 30 items. Total score: Range 0-100.	average 6 months
Secondary	Adverse Events (AEs) and Serious Adverse Events (SAEs) of administering VAX-NK/HCC combined with HAIC	The assessment will be measured by determining the number of patients that experience AEs and SAEs graded according to the NCI-CTCAE (Version 4.0)	average 6 months
Secondary	The proportions of T and NK cells	This will be measured by determining the relative percentages of CD4+CD8+ T cells and CD3- CD56+ NK cells in patients' peripheral blood.	average 6 months
Secondary	The lymphocyte/monocyte ratio (LMR)	LMR will be calculated by dividing the absolute lymphocyte count by the absolute monocyte count in patients' peripheral blood.	average 6 months
Secondary	The NK cell cytotoxicity	This will be measured by determining percent cell lysis of target cells (K562) in patients' peripheral blood.	average 6 months
Secondary	The serum cytokine levels	The serum concentrations of IFN-?, IL-10, and TGF-ß will be measured in patients' serum using the Enzyme-Linked immunosorbent assays.	average 6 months