Overview
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.
Description
Using a modified 3+3 dose escalation design, this study will enroll ~9 subjects 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.
Eligibility
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.)