RE002 T‑cell injection for KRAS G12D mutated solid tumors

RE002 T Cell Injection for the Treatment of KRAS G12D Mutated Solid Tumors, an Open-label Single-center Phase I Clinical Trial

This trial tests whether a personalized RE002 T‑cell infusion is safe and can shrink tumors in adults with advanced solid tumors that have a KRAS G12D mutation and are HLA‑A*11:01 positive.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Henan Cancer Hospital (Government)
• Drugs / interventions: chemotherapy, immunotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Zhengzhou, Henan)
• Trial ID: NCT06546150 on ClinicalTrials.gov

What this trial studies

This is a single-center, open‑label, single‑arm Phase 1 dose‑escalation trial using a 3+3 design to test safety and tolerability of a single infusion of gene‑edited RE002 T cells in up to 30 patients with advanced KRAS‑mutant solid tumors. Patients have peripheral blood collected for manufacture of autologous, gene‑edited T cells that are expanded in vitro and given after lymphodepleting chemotherapy at one of three escalating dose levels. The primary safety window for dose‑limiting toxicities (DLTs) is 28 days after infusion, with planned inpatient monitoring around lymphodepletion and infusion; dosing intervals between participants are staggered to manage safety. The protocol requires HLA‑A*11:01 positivity and a documented KRAS mutation, although the publicly provided text contains an inconsistency listing KRAS G12V in one place while the title and overall intent target KRAS G12D.

Who should consider this trial

Good fit: Adults aged 18–75 with advanced, pathologically confirmed solid tumors that are KRAS G12D mutant, HLA‑A*11:01 positive, have measurable disease, ECOG 0–1, and have exhausted or cannot tolerate standard treatments are the intended candidates.

Not a fit: Patients without the required KRAS mutation or HLA‑A*11:01 type, those with poor performance status, or those who cannot tolerate lymphodepleting chemotherapy are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the therapy could offer a targeted T‑cell option that controls or shrinks tumors driven by KRAS G12D.

How similar studies have performed: Prior preclinical work and early clinical experience with TCR‑T approaches show feasibility and anti‑tumor activity in some settings, but KRAS G12D‑targeted TCR‑T remains early‑stage and not yet widely proven.

Eligibility criteria

Inclusion Criteria:

1. Subjects voluntarily participate in the study and sign informed consent;
2. Age ≥18 years old and ≤75 years old;
3. Advanced malignant solid tumors with clear pathological diagnosis;
4. Standard therapies failed or cannot be tolerated or lacks effective treatments;
5. Have at least one measurable lesion;
6. During the trial screening period, the following two indicators must be met (the sponsor is responsible):

   HLA-A\* 11:01 positive; Tumor gene testing carries KRAS G12V mutation;
7. ECOG score 0-1 and expected survival time greater than 6 months;
8. Cardiac color ultrasound shows left ventricular ejection fraction ≥50%;
9. Laboratory examination results should meet the following specified indicators:

   White blood cell count ≧ 3.0×109/L;
   1. Absolute neutrophil count ≧ 1.5×109/L (without G-CSF and GM-CSF support, enter at least 14 days before group);
   2. Absolute lymphocyte count ≧ 0.5×109/L;
   3. Platelets (PLT) ≧ 75×109/L (no blood transfusion treatment in the first 14 days);
   4. Hemoglobin ≧ 100g/L (no blood transfusion treatment in the first 14 days);
   5. Prothrombin time international normalized ratio INR ≦ 1.5×upper limit of normal time, unless anticoagulant therapy was received;
   6. Partial prothrombin time (APTT) ≦ 1.5×upper limit of normal time, unless receiving antibiotics coagulation therapy;
   7. Serum creatinine ≦ 1.5mg/dL (or 132.6μmol/L);
   8. Aspartate aminotransferase (AST/SGOT) ≦ 2.5×ULN;
   9. Alanine aminotransferase (ALT/SGPT) ≦ 2.5×ULN;
   10. Total bilirubin (TBIL) ≦ 1.5×ULN;
   11. In patients with liver metastasis, aspartate aminotransferase and alanine aminotransferase need to be ≦ 5×ULN.
10. Women of childbearing age who have not undergone sterilization before menopause must agree to use effective contraception within at least 12 months from the beginning of the study to T cell infusion, and the serum pregnancy test is negative within 14 days before the first treatment;
11. Men who have not undergone sterilization must agree to use effective contraception from the beginning of the study to at least 12 months after T cell infusion;
12. During the entire trial period, you can regularly visit the participating research institutions for relevant testing, evaluation and management.

Exclusion Criteria:

1. Those who have received major surgery, conventional chemotherapy, large-area radiotherapy, immunotherapy or biological therapy anti-tumor treatment within 4 weeks before entering the trial;
2. Previous use of drugs targeting KRAS G12V mutations, including previous participation in cell therapy with similar targets Cellular testing and small molecule inhibitors targeting KRAS G12V mutations, etc.;
3. Allergic reactions are known to occur to any ingredient (such as dimethyl sulfoxide, cyclophosphamide, fludarabine) or structurally similar compounds treated in this trial;
4. Failure to recover from adverse reactions related to previous surgery or treatment to \< Grade 2 CTCAEV5.0;
5. Hypertension that remains uncontrolled after combined treatment with 2 drugs or clinically significant (such as active) Cardiovascular and cerebrovascular diseases, such as cerebrovascular accident (within 6 months before signing the informed consent form), myocardial infarction (within 6 months before signing the informed consent form), unstable angina, congestive heart failure classified as class II or above by the New York Heart Association, or severe arrhythmia that cannot be controlled with medication or has a potential impact on study treatment; the electrocardiogram showed obvious abnormality or average QTc interval ≧ 450ms for 3 consecutive times (at least 5 minutes interval);
6. Combined with other serious organic diseases and mental disorders;
7. Suffering from systemic active infections requiring treatment, including but not limited to active tuberculosis, known HIV positive patients or patients with clinically active hepatitis A, B, or C include virus carriers;
8. Have a history of inflammatory bowel disease and autoimmune diseases judged by the researcher to be unsuitable for this study (such as systemic lupus erythematosus, vasculitis, etc.);
9. Those who plan to use the following drugs within 4 weeks before cell therapy and during the study: long-term systemic use steroid hormones, hydroxyurea, immunomodulatory drugs (such as interleukin 2, alpha or gamma interferon, GM-CSF, mTOR inhibitors, cyclosporins, thymosin, etc.);
10. People with brain metastasis:

    1. Symptomatic brain metastasis should be ruled out. Patients with a previous history of symptomatic brain metastasis and stable symptoms after local treatment were enrolled in the group who did not need antiepileptic drugs and steroids at least 14 days before lymphocyte clearance.
    2. Subjects with asymptomatic brain metastasis without tumor-related brain edema, displacement, steroids or antiepileptic drugs can be enrolled.
    3. Subjects with meningitis or meningeal metastasis need to be excluded.
11. People with bleeding or thromboembolism tendency:

    1. Have clinically significant bleeding symptoms or obvious bleeding tendency within 2 weeks before the study;
    2. Have inherited or acquired bleeding and thrombosis tendencies;
    3. A serious arterial/venous thromboembolic event within the past 6 months.
12. Suffering from massive pericardial effusion or symptomatic thoracic or abdominal effusion;
13. Have received live attenuated vaccines within 4 weeks before cell infusion, or plan to receive this type of vaccine during the study;
14. History of organ allogeneic transplantation, allogeneic stem cell transplantation and renal replacement therapy;
15. Uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure;
16. Known alcohol and/or drug abusers;
17. Pregnant or breastfeeding women;
18. Have any coexisting medical conditions or diseases that the researcher determines may impair the conduct of this trial subjects;
19. No legal capacity/restricted capacity;
20. Have previously received any gene or cell therapy products.

Where this trial is running

Zhengzhou, Henan

• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)

Study contacts

• Study coordinator: Zi B Wang

Conditions KRAS G12D; T Cell Therapy