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

TingBo Liang

Status and phase

Enrolling

Phase 1

Conditions

Tumor, Solid

Treatments

Drug: NW-301V

Drug: NW-301D

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT06478251

NW-301-001

Details and patient eligibility

About

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.

Full description

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.

Enrollment

9 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.)