Solid Metastatic Tumor
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALNW-101C
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
Sponsors
Neowise Biotechnology
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A classic 3+3 model will be used to dose escalation,4 doses will be used: 4×10\^8±30%, 8×10\^8±30%, 15×10\^8±30% and 30×10\^8±30% TCR-T cells/ patients
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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)
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Dose-limiting toxicities(DLTs) of NW-101C in patients with solid malignant tumors | 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 | Through the study completion, an average of 2 years | Type, frequency and severity of adverse events assessed by CTCAE5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the AUC of NW-101C in patients with solid malignant tumors | 2 years following NW-101C infusion | Area under the Plasma concentration versus time curve(AUC) assessed centrally |
| Evaluate the Objective response rate (ORR) of NW-101C in patients with solid malignant tumors | 2 years following NW-101C infusion | Complete response (CR) and partial response (PR) assessed by investigators following RECIST1.1 criteria |
| Evaluate the Cmax of NW-101C in patients with solid malignant tumors | Through the study completion, an average of 2 years | Maximum Concentration(Cmax) assessed centrally |
| Evaluate the Tmax of NW-101C in patients with solid malignant tumors | Through the study completion, an average of 2 years | Time of Maximum Concentration assessed centrally |
Countries
China
Contacts
Primary ContactYuhui He
Outcome results
None listed