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.

Study Overview

• Status: Recruiting
• Conditions: Tumor, Solid
• Intervention / Treatment: Drug: NW-301V; Drug: NW-301D

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

Contacts and Locations

• Study Contact: Name: Rui Liu; Phone Number: 15377559472; Email: rui.liu@neowisebio.com
• Study Contact Backup: Name: Yuhui He; Phone Number: 13820064975; Email: yuhui.he@neowisebio.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Wuhan Union Hospital
      • Contact: Tao Zhang, MD, PHD; Phone Number: 862785871982; Email: 1277577866@qq.com
      • Contact: Zhenyu Lin, MD; Phone Number: 15827130393; Email: tojilin@gmail.com
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Wuhan Union Hospital
      • Contact: ZhenYu Lin

Participation Criteria

Eligibility Criteria

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

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NW-301V; NW-301V monotherapy in patients with Solid Tumors with KRAS G12V mutation	Drug: NW-301V; TCR-T cell targeting KRAS G12V mutation
Experimental: NW-301D; NW-301D monotherapy in patients with Solid Tumors with KRAS G12D mutation	Drug: NW-301D; TCR-T cell targeting KRAS G12D mutation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Safety	28 days of single infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 the completion of the study, with average of 2 years
Duration of response (DOR)	CR and PR, locally assessed using RECIST v1.1	through the completion of the study, with average of 2 years

Collaborators and Investigators

• Sponsor: Tao Zhang
• Collaborators: Neowise Biotechnology

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 26, 2024
• First Submitted That Met QC Criteria: June 26, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 27, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: NW-301-001

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
• product manufactured in and exported from the U.S.: No