Safety and Efficacy Study of TX103 CAR-T Cell Therapy for Recurrent or Progressive Grade 4 Glioma.
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-75
SponsorTcelltech Inc.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects must voluntarily participate in the study and sign a written informed consent document; subjects should be willing and able to follow and complete study procedures.
Male or female subjects aged 18 to 75 years (both inclusive).
Subject must have histologically diagnosed grade 4 glioma, such as glioblastoma, grade 4 astrocytoma, diffuse hemispheric glioma, according to 2021 WHO Classification of Tumors of the CNS. Subjects must have had experienced disease recurrence or progression* after surgery combined with Stupp regimen (concurrent radiotherapy and temozolomide (TMZ) followed by adjuvant TMZ) and are not candidate for re-resection. For subjects harboring specific gene mutations, such as NTRK gene fusion or BRAF V600E mutation, they must have also progressed on corresponding mutation-directed therapies before enrollment.
Subjects with confirmed B7-H3 positive* (≥30%) tumor expression by immunohistochemistry (IHC) in either primary or recurrent tumor tissue.
Disqualifiers
Pregnant or breastfeeding female subjects.
Serum HIV antibody positive, treponema pallidum serology positive; OR
Hepatitis B surface antigen (HBsAg) positive and peripheral blood HBV DNA test value exceeds the normal range; OR
Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive.
Trial design
Design model
Parallel
Treatments tested in this trial
Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
Biological/VaccineSafety Run-In: Dose:6×10\^7 CAR+ T cells Cohort A Single delivery route(Multi-dose)、Cohort B Dual delivery route(Multi-dose)： 3+3 dose escalation design： Dose Level 1: 6×10\^7 CAR+ T cells Dose Level 2: 1.5×10\^8 CAR+ T cells Dose Level 3: 2.5×10\^8 CAR+ T cells
Treatment groups
52 Participants
are divided into 3 treatment groupsGroup A: Safety Run-InExperimental treatment 1 intervention
Group B: Cohort A Single delivery route(Multi-dose)Experimental treatment 1 intervention
Group C: Cohort B Dual delivery route(Multi-dose)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Safety：Incidence of Dose Limiting Toxicity (DLT)
Type, incidence, and severity of dose limiting toxicities (DLTs) within 28 days after the first TX103 infusion.
Time frame
28 days after the first TX103 infusion.2
Safety：Incidence and severity of adverse events (AEs)
To evaluate the possible adverse events after TX103 infusion, including the incidence, and severity of AEs.
Time frame
six months post CAR-T cells infusion.Secondary outcomes
1
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.
Time frame
6 and 12 months post CAR-T cells infusion.2
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.
Time frame
6 and 12 months post CAR-T cells infusion.3
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.
Time frame
1 year post CAR-T cells infusion.4
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.
Time frame
1 year post CAR-T cells infusion.Other outcomes
1
The immunogenicity of TX103
Drug antibody (ADA) positive rate after infusion of TX103 cells.
Time frame
up to 12 months.2
The positive rate of replication competent lentivirus tests
Detect replication competent lentivirus (RCL).
Time frame
up to 15 years.3
Incidence of Secondary Malignancies
The frequency and occurrence of new, distinct cancerous growths that develop as a result of TX103.
Time frame
up to 15 years.4
Peak Concentration (Cmax) of TX103 CAR gene
Peak Concentration (Cmax) of TX103 CAR gene
Time frame
Up to 12 months.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov