Safety and Efficacy Study of TX103 CAR-T Cell Therapy for Recurrent or Progressive Grade 4 Glioma.
NCT Number: NCT06482905
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: High-grade Glioma|WHO Grade Ⅳ Glioma
Interventions: BIOLOGICAL: Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
Sponsor: Tcelltech Inc.
Collaborators: Beijing Tiantan Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 52
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-06
Completion Date: 2027-06
Locations: Beijing Tiantan Hospital, Beijing, Beijing, 100730, China

Summary:
This is a phase I, open-Label, single/multiple dose, dose-escalation study to evaluate the safety, tolerability and antitumor activity of anti-B7-H3 CAR-T cell injection (TX103) in subjects with recurrent or progressive Grade 4 Glioma.The study also plan to explore the Maximum Tolerated Dose (MTD) and determine the Recommended Phase II Dose (RP2D) of the CAR-T cell therapy.

Primary Outcome Measures: Safety：Incidence of Dose Limiting Toxicity (DLT), Type, incidence, and severity of dose limiting toxicities (DLTs) within 28 days after the first TX103 infusion., 28 days after the first TX103 infusion.|Safety：Incidence and severity of adverse events (AEs), To evaluate the possible adverse events after TX103 infusion, including the incidence, and severity of AEs., six months post CAR-T cells infusion.
Secondary Outcome Measures: Overall survival (OS), The proportion of subjects who have survived for more than 6 and12 months since the diagnosis of recurrent or progressive Grade 4 Glioma., 6 and 12 months post CAR-T cells infusion.|Post-relapse survival (PRS), The proportion of subjects who have survived for more than 6 and12 months since the diagnosis of recurrent or progressive Grade 4 Glioma., 6 and 12 months post CAR-T cells infusion.|Progression Free Survival (PFS), To evaluate the time from the start of TX103 therapy to disease progression (according to RANO2.0 criteria) or death from any cause, whichever occurs first. The proportion of progression-free subjects from the beginning of TX103 therapy to a fixed time point (6 months) after treatment (6-Mon PFS) will also be evaluated., 1 year post CAR-T cells infusion.|Disease Control Rate (DCR), To evaluate the proportion of subjects who achieved CR/PR/SD in the best overall response according to RANO2.0 criteria., 1 year post CAR-T cells infusion.|Duration of disease control (DDC), To evaluate the time from the first evaluation of tumor as CR, PR or SD to the first evaluation of PD or death from any cause., 1 year post CAR-T cells infusion.|Objective response rate (ORR), To evaluate the proportion of subjects who achieved CR/PR in the best response condition according to RANO2.0 criteria., 1 year post CAR-T cells infusion.|Time to Remission (TTR), To evaluate the time from the start of treatment to the first remission (CR/PR)., 1 year post CAR-T cells infusion.|Duration of Response (DOR), DOR after TX103 infusion, defined as the time from the first evaluation of the tumor as CR or PR to the first evaluation of PD or death from any cause., 1 year post CAR-T cells infusion.|Neurological function evaluated by NANO scale, Change in neurological function from baseline., 1 year post CAR-T cells infusion.|Quality of life score, Change in Quality of life score from baseline., 1 year post CAR-T cells infusion.
Other Outcome Measures: The immunogenicity of TX103, Drug antibody (ADA) positive rate after infusion of TX103 cells., up to 12 months.|The positive rate of replication competent lentivirus tests, Detect replication competent lentivirus (RCL)., up to 15 years.|Incidence of Secondary Malignancies, The frequency and occurrence of new, distinct cancerous growths that develop as a result of TX103., up to 15 years.|Peak Concentration (Cmax) of TX103 CAR gene, Peak Concentration (Cmax) of TX103 CAR gene, Up to 12 months.|Area under the concentration versus time curve (AUC) of TX103 CAR-T cells, Area under the concentration versus time curve (AUC) of TX103 CAR-T cells, Up to 12 months.|Peak concentration of cytokines, Peak concentration of IL-2, IL-4，IL-6, IL-8，IL-10，IFN-γ， TNF-a, Up to 12 months.