Overview
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.
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.
Eligibility
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 Exclusion criteria may apply)