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

NCT06364787 | Not Yet Recruiting Phase 1

• 1 other identifier: GDT-001-07-01
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (7)

• 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

Study Arms (2)

γδ T cells+ PD-1 monoclonal antibody+ targeted drugs

EXPERIMENTAL

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; Drug: Targeted drugs; Drug: PD-1 monoclonal antibody

PD-1 monoclonal antibody+ targeted drugs

ACTIVE COMPARATOR

PD-1 monoclonal antibody+ targeted drugs

Drug: Targeted drugs; Drug: PD-1 monoclonal antibody

Interventions

γδ T cells BIOLOGICAL

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.

γδ T cells+ PD-1 monoclonal antibody+ targeted drugs

Targeted drugs DRUG

Multi-target kinase inhibitors can act on VEGFR-1,VEGFR-2,VEGFR-3,FGFR1,PDGFR,cKit,Ret and other targets.

PD-1 monoclonal antibody+ targeted drugs; γδ T cells+ PD-1 monoclonal antibody+ targeted drugs

PD-1 monoclonal antibody DRUG

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.

PD-1 monoclonal antibody+ targeted drugs; γδ T cells+ PD-1 monoclonal antibody+ targeted drugs

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Patients combined with HAV, HEV, HIV or other infectious diseases.
• Acute infections, gastrointestinal bleeding, etc. occurred within 30 days before screening.
• Women who are pregnant (urine/blood pregnancy test positive) or lactating; patients with severe autoimmune diseases; patients with uncontrolled infectious diseases.
• Major organs dysfunction.
• 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.
• Allergic constitution, history of allergies to blood products, known to be allergic to test substances.
• 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.
• Patients currently participating in other clinical trials who may violate this treatment plan and observations.
• Those who are unable or unwilling to provide informed consent or who are unable to comply with the research requirements.
• 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.

Sponsors & Collaborators

• Beijing 302 Hospital: lead
• Chinese Academy of Medical Sciences: collaborator
• Beijing GD Initiative Cell Therapy Technology Co., Ltd.: collaborator

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

spartalizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Meng Fan-Ping, Ph.D

CONTACT

66933126-6019; drmengfanping@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: April 15, 2024
• Study Start: April 26, 2024
• Primary Completion: April 26, 2026
• Study Completion (Estimated): September 26, 2026
• Last Updated: April 15, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share