TCR-engineered T Cells (NW-101C) in Patients With Solid Malignant Tumors

Neowise Biotechnology

Status and phase

Enrolling

Phase 1

Conditions

Solid Metastatic Tumor

Treatments

Biological: NW-101C

Study type

Interventional

Funder types

Industry

Identifiers

NCT07266298

NW-101C-002

Details and patient eligibility

About

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.

Full 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.

Enrollment

24 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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)