T Cell Receptor Gene-Engineered T Cell Therapy Targeting KRAS Mutations in the Treatment of Subjects With Advanced Solid Tumor

An Open-Label, Dose-Escalation Phase I Clinical Study of T Cell Receptor Gene-Engineered T Cell Therapy Targeting KRAS Mutations in the Treatment of Subjects With Advanced Solid Tumor

An open label, two-cohort, dose-escalation clinical study to evaluate the safety, anti-tumor activity and pharmacokinetics/pharmacodynamic (PK/PD) of NW-301V and NW-301D in subjects with advanced solid tumor.

Using a modified 3+3 dose escalation design, this study will enroll ~9subjects to characterize the safety and preliminary anti-tumor activity of NW-301V and NW-301D in each cohort respectively. Eligible subjects will undergo leukapheresis for autologous cell product manufacturing, and will receive a 3-day lymphodepleting regimen consisting of cyclophosphamide and fludarabine, followed by a single-dose intravenous infusion of NW-301V or NW-301D. after NW-301V or NW-301D infusion, a low dose of IL-2 will be given subcutaneously for up to 10 days. following this intervention, subjects will be monitored for safety and AE, and tumor evaluation will be performed at pre-specified timepoints per protocol.

Key Inclusion Criteria:

• Age between 18-75 years
• Diagnosis of pathologically or histologically confirmed unresectable or advanced solid tumor, and have no standard treatment options available or unable to tolerate the currently available standard treatments
• HLA-A*11:01positive
• Tumor has KRAS G12V (NW-301V cohort) or G12D (NW-301D cohort) mutation
• 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.)

Key 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.)