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

A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SNC109 in Patients With Recurrent Glioblastoma

A phase I study to evaluate the safety, tolerance and pharmacokinetics of SNC109 in patients with rGBM

Study Overview

• Status: Enrolling by invitation
• Conditions: Recurrent Glioblastoma Multiforme (GBM)
• Intervention / Treatment: Drug: SNC109

Detailed Description

It is planned to recruit about 50 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 5×104 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): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥18，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) ≥50;
• The estimated survival time is ≥12 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: SNC109 CART; After the screening and evaluation, SNC-109 CAR-T Cells will be infusion.	Drug: SNC109; SNC-109 CAR-T Cells, first dose from 5×104 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 events	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
DLT	Incidence of DLT associated with CAR-T cell transfusion within 28 days of the first infusion	Up to 28 days after first infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Time maximum of SNC-109 Cell count and CAR vector copy number	Pharmacokinetic (PK) profile/parameter Tmax	within 2 years after first infusion
Pharmacokinetic (PK) profile/parameters Peak Plasma Concentration (Cmax) of SNC-109 Cell count and CAR vector copy number	Peak Plasma Concentration (Cmax)	within 2 years after first infusion
Pharmacokinetic (PK) profile/parameters Area under the plasma concentration versus time curve (AUC)	Area under the plasma concentration versus time curve (AUC) of SNC-109 Cell count	within 2 years after first infusion
Progression free survival (PFS) after infusion	The data of Overall survival (OS) after infusion	within 2 years after first infusion
Pharmacodynamic (PD) profile/parameters 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

Collaborators and Investigators

• Sponsor: Shanghai Simnova Biotechnology Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: September 2, 2024
• First Submitted That Met QC Criteria: September 26, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 26, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: GBM
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: SNC109-102

Drug and device information, study documents

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