A Phase I, Multicenter, Dose-escalation, Single-arm Study of PRAME Antigen-targeted TCR-T Cells(NW-101C) in the Treatment of Subjects With Advanced Solid Malignant Tumors.
概览
- 阶段
- 1 期
- 干预措施
- NW-101C
- 疾病 / 适应症
- 未指定
- 发起方
- Neowise Biotechnology
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Evaluate the Dose-limiting toxicities(DLTs) of NW-101C in patients with solid malignant tumors
- 状态
- 招募中
- 最后更新
- 4个月前
概览
简要总结
This clinical trial is a prospective, dose-escalation, multicenter, single- arm, Phase 1 clinical trial to evaluate the safety, tolerability, PK and preliminary clinical activity of PRAME Antigen-targeted TCR-T Cells (NW-101C) infusion in patients with previously heavily treated, metastatic solid malignant tumors.
详细描述
Using a classic 3+3 dose escalation design, this study will enroll \~24 subjects to characterize the safety and preliminary anti-tumor activity of NW-101C. SCREENING: Patient eligibility will be determined by protocol inclusion/exclusion criteria including HLA (human leukocyte antigen) and a biopsy (or collection of archival tumor tissue) for biomarker screening. Leukapheresis for potential manufacturing of the NW-101C cellular product may be performed,if patients are HLA-A\*02:01 positive and meet the eligibility criteria for leukapheresis. MANUFACTURING: NW-101C products will be made from the patients' white blood cells. TREATMENT: Lymphodepletion with cyclophosphamide and fludarabine will occur in the days before the NW-101C product infusion to improve the duration of time that NW-101C product stays in the body. The patient will be admitted to the hospital during the T-cell infusion until 28 days following NW-101C infusion. After the NW-101C product infusion, dose -limiting toxicities (DLT) will be assessed from the infusion of NW-101C until 28 days following the infusion of NW-101C.
研究者
入排标准
入选标准
- •Age between 18-75 years
- •Diagnosis of pathologically or histologically confirmed unresectable or advanced solid tumors and must have no standard treatment options available or unable to tolerate the currently available standard treatments
- •For patients with ovarian caner :Patients must have confirmed diagnosis of Platinum-resistant ovarian epithelial carcinoma(PROC)
- •HLA-A\*02:01positive
- •Patient's tumor must express PRAME assessed by central lab,Retrospective testing will be required for patients that qualify.
- •Adequate organ function prior to apheresis and lymphodepleting chemotherapy
- •ECOG performance status of 0-1
- •At least one tumor lesion measurable according to RECIST 1.1
- •(Additional protocol-defined Inclusion criteria may apply)
排除标准
- •Received the following treatments: Cytotoxic chemotherapy within 2 weeks prior to apheresis and within 1 week prior to lymphodepletion; Treatment with antibodies (including but not limited to those with monoclonal antibodies and immune checkpoint inhibitors) or other biologic therapy within 2 weeks prior to apheresis and within 1 week prior to lymphodepletion; Immunosuppressive agents (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutic agents, mycophenolate mofetil, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL-6, or anti-IL-6 receptor) within 2 weeks prior to apheresis and within 1 week prior to lymphodepletion
- •History of allergic reactions to cyclophosphamide, fludarabine, or any other chemical or biological components of the drugs used in this study
- •History of chronic or recurrent severe autoimmune disease, or active immune disease requiring treatment with steroids or other immunosuppressive agents within 1 year prior to enrollment
- •Have symptomic CNS metastases
- •Have leptomeningeal disease or carcinomatous meningitis
- •Have ongoing or active infection
- •Active infections with HIV, HBV, HCV, or syphilis
- •Breastfeeding or pregnant
- •(Additional protocol-defined Exclusion criteria may apply)
研究组 & 干预措施
NW-101C dose 1-4
干预措施: NW-101C
结局指标
主要结局
Evaluate the Dose-limiting toxicities(DLTs) of NW-101C in patients with solid malignant tumors
时间窗: 28 days following NW-101C infusion
Type, frequency and severity of adverse events assessed by CTCAE5.0
Evaluate the Maximum Tolerated Dose (MTD) of NW-101C in patients with solid malignant tumors
时间窗: Through the study completion, an average of 2 years
Type, frequency and severity of adverse events assessed by CTCAE5.0
次要结局
- Evaluate the AUC of NW-101C in patients with solid malignant tumors(2 years following NW-101C infusion)
- Evaluate the Objective response rate (ORR) of NW-101C in patients with solid malignant tumors(2 years following NW-101C infusion)
- Evaluate the Tmax of NW-101C in patients with solid malignant tumors(Through the study completion, an average of 2 years)
- Evaluate the Cmax of NW-101C in patients with solid malignant tumors(Through the study completion, an average of 2 years)