KRAS-Specific Autologous TCR-T Cell Therapy for KRAS Mutation in Advanced Solid Tumors

NCT06767046 | Active Not Recruiting Phase 1

• 1 other identifier: CRTKVA11-2311C
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, open-label, single-arm, dose-escalation study aimed at evaluating the safety and preliminary efficacy of KRAS-specific autologous TCR-T cells in patients with advanced solid tumors harboring KRAS G12V mutation.

Conditions

Colorectal; Pancreatic; Non-small Cell Lung Cancer (NSCLC)

Keywords

KRAS G12V; immunotherapy; T cell; Adoptive cell therapy; T cell receptor; TCR

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs)

  Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs)

  2 years

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  2 years

• Disease Control Rate (DCR)

  2 years

• Duration of Response (DOR)

  2 years

• Progression-Free Survival (PFS)

  2 years

• Overall Survival (OS)

  2 years

Study Arms (1)

KRAS-specific Autologous TCR-T cell injection

EXPERIMENTAL

KRAS-specific Autologous TCR-T cell injection (5×10⁹, 1×10¹°, or 2×10¹° TCR-T cells per dose) with preconditioning lymphodepletion using Fludarabine and Cyclophosphamide, followed by IL-2 support

Drug: KRAS-specific Autologous TCR-T cell injection

Interventions

KRAS-specific Autologous TCR-T cell injection DRUG

Drug1 : Fludarabine + Cyclophosphamide Drug2 :Interleukin 2 Drug3 :KRAS-specific Autologous TCR-T cell injection

Also known as: CRTKVA11-N04

KRAS-specific Autologous TCR-T cell injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-70 years.
• Histologically or cytologically confirmed advanced solid tumors (e.g., colorectal cancer, pancreatic cancer, NSCLC) with KRAS G12V mutations and HLA-A\*11:01 genotype.
• Failed standard therapies or no effective treatment available.
• ECOG performance status of 0-1.
• Life expectancy of ≥3 months.
• Presence of at least one measurable lesion as defined by RECIST 1.1 criteria.
• Female patients of childbearing potential must agree to use highly effective contraceptive methods during the study and for at least 6 months after the last dose. A negative pregnancy test within 7 days prior to treatment initiation is required.
• Written informed consent provided by the patient, with an expectation of compliance with study procedures.

You may not qualify if:

• Prior treatment with gene-modified T-cell therapies.
• Current treatment with T-cell suppressive agents (e.g., cyclophosphamide, FK506, tripterygium glycosides) or T-cell stimulants.
• Chemotherapy, targeted therapy, immunotherapy, or investigational drugs administered within 2 weeks, or radiotherapy within 4 weeks prior to enrollment.
• Significant organ dysfunction, as evidenced by:
• leukocytes\<3.0 x 109/L
• absolute neutrophil count \>1.5 x 109/L
• hemoglobin\<90g/L
• platelets \<100 x 109/L
• Creatinine\>1.5×ULN or creatinine clearance \<50mL/min
• lymphocytes\<0.5 x 109/L
• total bilirubin\>3×ULN; ALT/AST\>3×ULN (or \>5× ULN in patients with liver metastases)
• INR/APTT\>1.5×ULN；
• SpO2≤93%
• Presence of serious diseases and comorbidities, including but not limited to: severe heart disease, cerebrovascular disease, seizures, poorly controlled diabetes (such as Type 1 diabetes or insulin-dependent diabetes), pancreatic dysfunction, severe infections, active gastrointestinal ulcers, gastrointestinal bleeding, mechanical or paralytic bowel obstruction, pulmonary fibrosis, renal failure, respiratory failure, etc.
• History of severe cardiovascular diseases within the past 6 months, including but not limited to: myocardial infarction, severe or unstable angina, coronary artery or peripheral artery bypass surgery, New York Heart Association (NYHA) Class III or IV heart failure, etc.

Sponsors & Collaborators

• Corregene Biotechnology Co., Ltd: lead

Study Sites (1)

Capital Medical University Affiliated Beijing Ditan Hospital

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2025
• First Posted: January 9, 2025
• Study Start: February 18, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)