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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
4 dosage of NW-101C will be tested in this study using classic 3+3 dose escalation approach: 4×10\^8±30%, 8×10\^8±30%,15×10\^8±30% and 30×10\^8±30% TCR-T+ cells
Beijing Cancer hosptial
Beijing, Beijing Municipality, China
RECRUITINGEvaluate the Dose-limiting toxicities(DLTs) of NW-101C in patients with solid malignant tumors
Type, frequency and severity of adverse events assessed by CTCAE5.0
Time frame: 28 days following NW-101C infusion
Evaluate the Maximum Tolerated Dose (MTD) of NW-101C in patients with solid malignant tumors
Type, frequency and severity of adverse events assessed by CTCAE5.0
Time frame: Through the study completion, an average of 2 years
Evaluate the AUC of NW-101C in patients with solid malignant tumors
Area under the Plasma concentration versus time curve(AUC) assessed centrally
Time frame: 2 years following NW-101C infusion
Evaluate the Objective response rate (ORR) of NW-101C in patients with solid malignant tumors
Complete response (CR) and partial response (PR) assessed by investigators following RECIST1.1 criteria
Time frame: 2 years following NW-101C infusion
Evaluate the Cmax of NW-101C in patients with solid malignant tumors
Maximum Concentration(Cmax) assessed centrally
Time frame: Through the study completion, an average of 2 years
Evaluate the Tmax of NW-101C in patients with solid malignant tumors
Time of Maximum Concentration assessed centrally
Time frame: Through the study completion, an average of 2 years
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