Clinical trial NCT05868083: The Safety and Efficacy of SNC-109 CAR-T Cells Therapy the Recurrent Glioblastoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Recurrent Glioblastoma Multiforme
Keywords: CAR-T
GBM
Lead sponsor: Shanghai Simnova Biotechnology Co.,Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Chinese PLA General Hospital
First posted: 2023-05-22
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment related adverse everts
timeFrame: Up to 28 days after first infusion
measure: Cmax of SNC-109 Cell count
timeFrame: within 2 years after first infusion
measure: Tmax of SNC-109 Cell count
timeFrame: within 2 years after first infusion
measure: AUC of SNC-109 Cell count
timeFrame: within 2 years after first infusion
measure: Cmax of SNC-109 CAR vector copy number
timeFrame: within 2 years after first infusion
measure: Tmax of SNC-109 CAR vector copy number
timeFrame: within 2 years after first infusion
measure: AUC of SNC-109 CAR vector copy number
timeFrame: within 2 years after first infusion
measure: Other relevant PK parameters
timeFrame: within 2 years after first infusion
Secondary outcomes:
measure: Objective response rate (ORR) after infusion
timeFrame: within 2 years after first infusion
measure: Progression free survival (PFS) after infusion
timeFrame: within 2 years after first infusion
measure: Overall survival (OS) after infusion
timeFrame: within 2 years after first infusion
measure: Efficacy assesment for the treatment according to iRANO
timeFrame: within 2 years after first infusion
measure: Changes of Cytokines after infusion
timeFrame: within 2 years after first infusion
measure: Concentration of Human anti-chimeric antibody (HACA)
timeFrame: within 2 years after first infusion
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
Study officials:
References: