T Cell Receptor Gene-Engineered and Dominant Negative TGF-β Receptor 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 and Dominant Negative TGF-β Receptor T Cell Therapy Targeting KRAS Mutations in the Treatment of Subjects With Advanced Solid Tumor

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

Study Overview

• Status: Active, not recruiting
• Conditions: Tumor
• Intervention / Treatment: Drug: NW-301VT

Detailed 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-301VT . 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-301VT. following this intervention, subjects will be monitored for safety and AE, and tumor evaluation will be performed at pre-specified timepoints per protocol.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 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, CMV or syphilis
• Breastfeeding or pregnant

(Additional protocol-defined Exclusion criteria may apply.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NW-301VT monotherapy in patients with Solid Tumors with KRAS G12V mutation	Drug: NW-301VT; TCR-T cell targeting KRAS G12V mutation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Safety	28 days following NW-301VT infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	CR and PR, locally assessed using RECIST v1.1	Through study completion, an average of 2 year
Objective response rate (ORR)	complete response (CR) and partial response (PR) based on best overall response (BOR), locally assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2032

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NW-301VT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not provided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No