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

Phase 1

Recruiting

• Conditions: Tumor, Solid
• Interventions: Drug: NW-301V; Drug: NW-301D

• Registration Number: NCT06484556
• Lead Sponsor: Tao Zhang

Brief Summary

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.

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-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.

Study Timeline

• Study Start: 2024-06-19
• Study First Submitted: 2024-06-26
• Study First Submitted QC: 2024-06-26
• Study First Posted: 2024-07-03
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-27
• Last Update Posted: 2025-07-31
• Primary Completion: 2026-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 9

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NW-301V	NW-301V	NW-301V monotherapy in patients with Solid Tumors with KRAS G12V mutation
NW-301D	NW-301D	NW-301D monotherapy in patients with Solid Tumors with KRAS G12D mutation

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT)	28 days of single infusion	Safety

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	through the completion of the study, with average of 2 years	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
Duration of response (DOR)	through the completion of the study, with average of 2 years	CR and PR, locally assessed using RECIST v1.1

Trial Locations

Locations (1)

Wuhan Union Hospital; 🇨🇳 Wuhan, Hubei, China