A Phase I, Open-Label, Single/Multiple Dose, Dose-escalation Study to Evaluate the Safety, Tolerability and Antitumor Activity of TX103 CAR-T Cell Injection (TX103) in Subjects With Recurrent or Progressive Grade 4 Glioma.
概览
- 阶段
- 1 期
- 干预措施
- Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
- 疾病 / 适应症
- High-grade Glioma
- 发起方
- Tcelltech Inc.
- 入组人数
- 52
- 试验地点
- 5
- 主要终点
- Safety：Incidence and severity of adverse events (AEs)
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
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.
详细描述
Eligible subjects will be enrolled into two sequential dose-escalating cohorts (i.e., A and B), and will be administrated TX103. Cohort A will receive TX103 exclusively through intraventricular (ICV) delivery, while cohort B will undergo dual intracavitary (ICT) and ICV delivery. Patients in each individual cohort will receive two TX103 infusions on Day 1 and 8 respectively, followed by a 14-day observation period in a 21-day treatment cycle. Three escalating dosage levels are planned for each cohort. Both Cohorts A and B will adopt the traditional 3+3 dose escalation design with each dose level enrolled with 3 to 6 patients. The starting dose will be 6 × 10\^7 CAR+ T cells (i.e., Dose Level 1, DL1). Dose limiting toxicities (DLTs) will be assessed during the first cycle .
研究者
入排标准
入选标准
- •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.
- •\* Disease recurrence or progression must be confirmed by radiographic or histopathological diagnosis.
- •Subjects with confirmed B7-H3 positive\* (≥30%) tumor expression by immunohistochemistry (IHC) in either primary or recurrent tumor tissue.
- •\*B7-H3 positive rate is defined as the percentage of B7-H3 positive tumor cells in non-necrotic tumor tissue.
- •Subjects with KPS score of ≥
- •Subjects should have adequate venous access for collection of peripheral blood mononuclear cells (PBMCs).
- •Subjects with left ventricular ejection fraction (LVEF) ≥ 40% within one month prior to the first dose.
- •Subjects with oxygen saturation ≥95% under the resting state.
排除标准
- •Pregnant or breastfeeding female subjects.
- •Subjects with viral infection during the screening period:
- •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.
- •Medical history and concomitant diseases:
- •Subjects who have received carmustine extended-release implantation surgery within 6 months;
- •Subjects with known or suspected active autoimmune diseases, including but not limited to Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.;
- •Subjects who are receiving systemic immunosuppressive agents or subjects who need to use immunosuppressive agents for a long-time during treatment, except for intermittent topical, inhaled, or intranasal glucocorticoid therapy;
- •Subjects with uncontrolled mental disorders, or who, in the Investigator's opinion, have a medical history or a history of mental states that may increase the risks associated with study participation or study drug administration, or that may interfere with the results;
研究组 & 干预措施
Safety Run-In
Single-dose administration of TX103 via intraventricular(ICV) or intracavitary (ICT) .
干预措施: Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
Cohort A Single delivery route(Multi-dose)
Administration of TX103 via intraventricular(ICV) on Days 1 and 8 in a 21-day treatment cycle.
干预措施: Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
Cohort B Dual delivery route(Multi-dose)
Administration of TX103 on Day 1 via intracavitary (ICT) and on Day 8 via intraventricular(ICV) in a 21-day treatment cycle.
干预措施: Anti-B7-H3 Chimeric Antigen Receptor T-Cell (CAR-T Cell) Injection/TX103
结局指标
主要结局
Safety：Incidence and severity of adverse events (AEs)
时间窗: six months post CAR-T cells infusion.
To evaluate the possible adverse events after TX103 infusion, including the incidence, and severity of AEs.
Safety：Incidence of Dose Limiting Toxicity (DLT)
时间窗: 28 days after the first TX103 infusion.
Type, incidence, and severity of dose limiting toxicities (DLTs) within 28 days after the first TX103 infusion.
次要结局
- Overall survival (OS)(6 and 12 months post CAR-T cells infusion.)
- Duration of Response (DOR)(1 year post CAR-T cells infusion.)
- Neurological function evaluated by NANO scale(1 year post CAR-T cells infusion.)
- Time to Remission (TTR)(1 year post CAR-T cells infusion.)
- Progression Free Survival (PFS)(1 year post CAR-T cells infusion.)
- Quality of life score(1 year post CAR-T cells infusion.)
- Post-relapse survival (PRS)(6 and 12 months post CAR-T cells infusion.)
- Disease Control Rate (DCR)(1 year post CAR-T cells infusion.)
- Duration of disease control (DDC)(1 year post CAR-T cells infusion.)
- Objective response rate (ORR)(1 year post CAR-T cells infusion.)