The Safety and Efficacy of SNC-109 CAR-T Cells Therapy the Recurrent Glioblastoma

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of SNC-109 CAR-T Cell Therapy in Subjects With Recurrent Glioblastoma

This is a single arm clinical study to estimate the safety, tolerability and pharmacokinetic (PK) characteristics of Chimeric Antigen Receptor-modified T cells (CAR-T) SNC-109 in patients with recurrent glioblastoma (r-GBM) and preliminarily evaluate the effectiveness, the immunogenicity of the product, as well as their correlation between the changes of cytokines from baseline level after cellular infusion.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Glioblastoma Multiforme
• Intervention / Treatment: Drug: SNC-109 CAR-T Cells

Detailed Description

It is planned to recruit about 16 patients with rGBM subjects. The protocol consists of screening period, Lymphocytes apheresis period, Operation period, pre-infusion evaluation (-2~-1 days), infusion (day 0), infusion observation (day 1-post infusion), and follow-up period (last infusion-720 days). The incidence of dose limitation toxicity (DLT) will be observed within 28 days after the first infusion. Subjects in this study will receive multiple infusions, starting with 2×104 CAR+ T cells/dose in the first subject, and the Safety Review Committee (SRC) will evaluate the subsequent dosing regimen, dose, infusion interval, and number of treatment cycles. Subsequent subjects will be evaluated by the SRC on the basis of available PK and safety data, and the SRC will determine the dosing regimen, dose, infusion interval and number of treatment cycles based on observed evidences.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Chinese PLA General Hospital
    • Contact: Ling Chen; Phone Number: 8610-66887329; Email: chen_ling301@163.com
    • Principal Investigator: Ling Chen, MD/PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18 and ≤70，both sexes;
• Diagnosed with a history of glioblastoma, and the recurrent glioblastoma has confirmed by histological/molecular pathology (including astrocytoma World Health Organization (WHO) Grade 4);
• Karnofsky (KPS) ≥60;
• The estimated survival time is ≥8 weeks;
• Blood pregnancy tests for women of childbearing age are negative;
• The patient himself/herself, and/or his/her legal guardian, agree to participate in the trial and sign the informed consent form.

Exclusion Criteria:

• Known allergies to study drugs or drugs that may be used in the study;
• Severe concurrent diseases in the heart, lungs, liver, or other vital organs;
• Hypertension is poorly controlled or accompanied by hypertensive crisis or hypertensive encephalopathy;
• In addition to the glioblastoma, with other severe central nervous system diseases or complications or aggressive malignancies;
• Long-term use of immunosuppressant drugs, or large doses of steroids;
• Received live or attenuated vaccine or other surgery had no related to GBM within 4 weeks prior to Lymphocytes apheresis;
• Lymphocytes apheresis or cell infusion combined with infection or unexplained fever.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SNC-109 CAR-T Cells; After the operation and pre-infusion evaluation, SNC-109 CAR-T Cells will be evaluated.	Drug: SNC-109 CAR-T Cells; SNC-109 CAR-T Cells, first dose from 2×104 CAR+ T Cells, treatment follows the operation and the next dose would be deiced by SRC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment related adverse everts	Incidence of adverse events associated with CAR-T cell transfusion within 28 days of the first infusion, abnormal and clinical significant laboratory results	Up to 28 days after first infusion
Cmax of SNC-109 Cell count	SNC-109 cell count maximum (Cmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)	within 2 years after first infusion
Tmax of SNC-109 Cell count	SNC-109 cell count time to Cmax(Tmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)	within 2 years after first infusion
AUC of SNC-109 Cell count	SNC-109 cell count area under the curve (AUC) in peripheral blood (PB) and cerebrospinal fluid (CSF)	within 2 years after first infusion
Cmax of SNC-109 CAR vector copy number	SNC-109 CAR vector copy number (VCN) maximum (Cmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)	within 2 years after first infusion
Tmax of SNC-109 CAR vector copy number	SNC-109 CAR vector copy number (VCN) time to Cmax(Tmax) in peripheral blood (PB) and cerebrospinal fluid (CSF)	within 2 years after first infusion
AUC of SNC-109 CAR vector copy number	SNC-109 CAR vector copy number (VCN) area under the curve (AUC) in peripheral blood (PB) and cerebrospinal fluid (CSF)	within 2 years after first infusion
Other relevant PK parameters	Other relevant PK parameters in peripheral blood (PB) and cerebrospinal fluid (CSF)	within 2 years after first infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) after infusion	The data of objective response rate (ORR) after infusion	within 2 years after first infusion
Progression free survival (PFS) after infusion	The data of Progression free survival (PFS) after infusion	within 2 years after first infusion
Overall survival (OS) after infusion	The data of Overall survival (OS) after infusion	within 2 years after first infusion
Efficacy assesment for the treatment according to iRANO	Assessment of disease response rates according to the Immunological Response Assessment in Neuro-Oncology (iRANO)	within 2 years after first infusion
Changes of Cytokines after infusion	Changes of cytokines (such as Interleukin-6, Interleukin-8 etc.) in peripheral blood (PB) and cerebrospinal fluid (CSF) pre-and post- infusion and at each of the main follow-up time points, and the time to recovery	within 2 years after first infusion
Concentration of Human anti-chimeric antibody (HACA)	Detection of changes in peripheral blood and cerebrospinal fluid Human anti-chimeric antibody (HACA)	within 2 years after first infusion

Collaborators and Investigators

• Sponsor: Shanghai Simnova Biotechnology Co.,Ltd.
• Collaborators: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: April 18, 2023
• First Submitted That Met QC Criteria: May 11, 2023
• First Posted (Actual): May 22, 2023

Study Record Updates

• Last Update Posted (Estimated): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: CAR-T; GBM
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Disease Attributes; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Recurrence
• Other Study ID Numbers: SNC-109-101

Drug and device information, study documents

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