Allogeneic Gamma-delta T Cells Combined With Targeted Therapy and Immunotherapy in a Phase 1 Clinical Trial for First-line Treatment of Hepatocellular Carcinoma

The Safety and Efficacy Assessment of Allogeneic γδ T Cells Combined With Targeted Therapy and Immunotherapy in Hepatocellular Carcinoma Patients

The purpose of this study is to evaluate the safety and efficacy of allogeneic γδ T cells combined with targeted therapy and PD-1 monoclonal antibody in first-line treatment of patients with hepatocellular carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: γδ T cells; Drug: Targeted drugs; Drug: PD-1 monoclonal antibody

Detailed Description

This is a double-arm, single-center, randomized, open label phase I clinical trial to evaluate the efficacy and safety of the combination of ex-vivo expanded allogeneic γδ T cells plus targeted therapy and PD-1 monoclonal antibody in patients with BCLC stage B or C hepatocellular carcinoma (HCC). A typical 3+3 dose-escalation design will be used to determine the optimal dose level of γδ T cells based on the incidence of dose-limiting toxicity (DLT). The initial infusion dose level will start from 1×10^8/kg to 4×10^8/kg in every 3 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Meng Fan-Ping, Ph.D; Phone Number: 66933126-6019; Email: drmengfanping@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients should sign informed consent form voluntarily before the trail and comply with the requirements of this study.
2. Age 18 years up to the age of 75 (≤75), gender unlimited.
3. Hepatocellular Carcinoma diagnosed according to the 2018 edition of the EASL guidelines.
4. BCLC stage B or C.
5. Liver function: Child-Pugh class A/B (5-9).
6. Eastern Cooperative Oncology Group (ECOG) Performance score≤1.
7. No previous antitumor therapy.
8. Life expectancy ≥ 6 months.
9. Patients combined with HBV infection require antiviral treatment with nucleoside analogues; patients combined with HCV infection require direct-acting antiviral agent (DAA) treatment.
10. Adequate organ and marrow function (within 4 weeks prior to study treatment initiation).
11. Male and female patients of reproductive potential must agree to use birth control during the study and for at least 30 days post study.
12. Capable of understanding and complying with the study protocol requirements ( including follow-up visit and examinations).
13. Be willing to signed a written informed consent document before enrollment.

Exclusion Criteria:

1. Patients combined with HAV, HEV, HIV or other infectious diseases.
2. Acute infections, gastrointestinal bleeding, etc. occurred within 30 days before screening.
3. Women who are pregnant (urine/blood pregnancy test positive) or lactating; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.
4. Major organs dysfunction.
5. Combined with other severe organic diseases or mental illnesses, including any uncontrolled clinically significant systematic diseases such as urinary, circulatory, respiratory, neurological, psychiatric, digestive, endocrine and immune diseases.
6. Allergic constitution, history of allergies to blood products, known to be allergic to test substances.
7. Immunosuppressive or systemic cytotoxic drugs may require within 6 months prior to screening or during the study; 6 months prior to screening accepted other cell therapies including NK, CIK, DC, CTL and stem cell therapy etc.
8. Patients currently participating in other clinical trials who may violate this treatment plan and observations.
9. Those who are unable or unwilling to provide informed consent or who are unable to comply with the research requirements.
10. Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed: patients with any serious acute or chronic physical or mental illness, or laboratory abnormalities.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: γδ T cells+ PD-1 monoclonal antibody+ targeted drugs; Patients will receive 4 cycles of ex-vivo expanded allogeneic γδ T cells treatments, at three-weeks' intervals. Ex-vivo expanded γδ T cells are transfused to patients in a typical 3+3 dose-escalation design (Dose escalation, 1×10^8/kg, 2×10^8/kg,4×10^8/kg).	Biological: γδ T cells; Cells will be extracted from a healthy donor by apheresis, followed by ex-vivo expansion and activation. The ex-vivo expanded γδ T cells from donors will be adoptively transfused.; Drug: Targeted drugs; Multi-target kinase inhibitors can act on VEGFR-1,VEGFR-2,VEGFR-3,FGFR1,PDGFR,cKit,Ret and other targets.; Drug: PD-1 monoclonal antibody; Humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth.
Active Comparator: PD-1 monoclonal antibody+ targeted drugs	Drug: Targeted drugs; Multi-target kinase inhibitors can act on VEGFR-1,VEGFR-2,VEGFR-3,FGFR1,PDGFR,cKit,Ret and other targets.; Drug: PD-1 monoclonal antibody; Humanized programmed death receptor (PD-1) monoclonal antibody that binds to PD- and prevents binding of PD-1 with programed death ligands 1 (PD-L1) and PD-L2. It can function to activate cytotoxic T lymphocytes and inhibit tumor growth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation: Incidence of Adverse events (AEs)	Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).	up to 60 weeks
Safety evaluation: Dose limited toxicity (DLTs)	The incidence, characteristic and severity of DLTs will be recorded and assessed.	up to 60 weeks
Safety evaluation: Maximum-tolerated dose (MTD)	MTD or clinical recommended dose will be recorded and evaluated.	up to 60 weeks
Efficacy evaluation: Objective Response Rate(ORR)	Objective clinical response will be assessed by investigators	up to 15months
Efficacy evaluation: Duration of Response(DOR)	The duration of objective response in patients will be recorded until 15months after the start of 1st cycle of treatment	up to 15months
Efficacy evaluation: Progress Free Survival(PFS)	Observation for progression-free survival (PFS) will be recorded until 15 months after the start of 1st cycle of treatment	up to 15months
Efficacy evaluation: Overall Survival (OS)	Observation for overall survival l (OS) will be recorded until 15 months after the start of 1st cycle of treatment.	up to 15months

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Collaborators: Beijing GD Initiative Cell Therapy Technology Co., Ltd.; Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): April 26, 2024
• Primary Completion (Estimated): April 26, 2026
• Study Completion (Estimated): September 26, 2026

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: GDT-001-07-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No