Allogeneic Gamma-delta T Cells Combined With Targeted Therapy and Immunotherapy in a Phase 1 Clinical Trial of Hepatocellular Carcinoma Resistant to PD-1 Monoclonal Antibody

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06364800
• Other study ID #: GDT-001-07-02
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: April 26, 2024
• Est. completion date: September 26, 2026

Study information

• Verified date: April 2024
• Source: Beijing 302 Hospital
• Contact: Fan-Ping Meng, Ph.D
• Phone: 66933126-6019
• Email: drmengfanping[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 patients with hepatocellular carcinoma resistant to PD-1 monoclonal antibody. Hepatocellular Carcinoma

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: September 26, 2026
• Est. primary completion date: April 26, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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. Treated with standard treatment options (anti-PD-1, targeted drugs) =3months and experiencing progressive disease according to RECIST 1.1.

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). 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• ?d T cells
Cells will be extracted from a healthy donor by apheresis, followed by ex-vivo expansion and activation. The ex-vivo expanded ?d T cells from donors will be adoptively transfused.

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

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
Beijing 302 Hospital	Beijing GD Initiative Cell Therapy Technology Co., Ltd., Chinese Academy of Medical Sciences

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Safety evaluation: Dose limited toxicity (DLTs)	The incidence, characteristic and severity of DLTs will be recorded and assessed.	up to 60 weeks
Primary	Efficacy evaluation: Objective Response Rate(ORR)	Objective clinical response will be assessed by investigators up to 15months	up to 15months
Primary	Efficacy evaluation: Duration of Response(DOR)	he duration of objective response in patients will be recorded until 15months after the start of 1st cycle of treatment	up to 15months
Primary	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
Primary	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