RE001 T Cell Injection for the Treatment of KRAS G12V Mutated Solid Tumors

NCT06545201 | Not Yet Recruiting Phase 1

• 1 other identifier: RE00120231204
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

At present, there is an urgent need for new drugs for kirsten rat sarcoma viral oncogene (KRAS) mutant tumors in clinic. Preclinical studies support the specificity, safety and anti-tumor activity of RE001. Previous similar studies suggest the feasibility of T cell receptor engineered T cell therapy (TCR-T) treatment, and measures have been taken to ensure the safe administration of RE001 and the close monitoring and management of adverse events. To sum up, RE001 has controllable safety and anti-tumor activity on KRAS mutant solid tumor, which can be preliminarily studied to provide support for clinical research of patients with advanced solid tumor.

Conditions

KRAS G12V; T Cell Therapy

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR).

  Defined as the proportion of subjects with confirmed CR and PR.

  24-36 months

Secondary Outcomes (1)

• Duration of response (DOR).

  24-36 months

Other Outcomes (5)

• Disease control rate (DCR).

  24-36 months

• Stable disease (DOSD).

  24-36 months

• Progression-free survival (PFS).

  24-36 months

Study Arms (1)

RE001T cell adoptive immunotherapy

EXPERIMENTAL

3+3 dose increasing design was adopted, and the dose increasing scheme was as follows (deviation 30%): low dose group: 4×109, middle dose group: 8×109, and high dose group: 1.6×1010. If the subjects in the lower dose group continue to benefit clinically after the first T cell infusion treatment, the second T cell infusion treatment can be carried out after the researcher's suggestion and the sponsor's consent. The second infusion can be carried out within 6 months of the disease progression, and the interval between the last infusion and the last infusion is at least 8 weeks.

Biological: RE001 T cell

Interventions

RE001 T cell BIOLOGICAL

All subjects who met the entry and exit criteria and signed the informed consent form were observed in hospital at the beginning of lymphocyte clearance chemotherapy, with the dosage of cyclophosphamide (600-800mg/m\^2/days,-5,-4 days) and fludarabine (25-30mg/m\^2/days,-5,-4,-3 days), at least two days after the completion of lymphocyte clearance chemotherapy.

RE001T cell adoptive immunotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects voluntarily participate in the study and sign informed consent;
• Age ≥18 years old and ≤75 years old;
• Advanced malignant solid tumors with clear pathological diagnosis;
• Standard therapies failed or cannot be tolerated or lacks effective treatments;
• Have at least one measurable lesion;
• 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;
• ECOG score 0-1 and expected survival time greater than 6 months;
• Cardiac color ultrasound shows left ventricular ejection fraction ≥50%;
• Laboratory examination results should meet the following specified indicators:
• White blood cell count ≧ 3.0×109/L;
• Absolute neutrophil count ≧ 1.5×109/L (without G-CSF and GM-CSF support, enter at least 14 days before group);
• Absolute lymphocyte count ≧ 0.5×109/L;
• Platelets (PLT) ≧ 75×109/L (no blood transfusion treatment in the first 14 days);
• Hemoglobin ≧ 100g/L (no blood transfusion treatment in the first 14 days);

You may not qualify if:

• 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;
• 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.;
• Allergic reactions are known to occur to any ingredient (such as dimethyl sulfoxide, cyclophosphamide, fludarabine) or structurally similar compounds treated in this trial;
• Failure to recover from adverse reactions related to previous surgery or treatment to \< Grade 2 CTCAEV5.0;
• 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);
• Combined with other serious organic diseases and mental disorders;
• 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;
• 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.);
• 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.);
• People with brain metastasis:
• 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.
• Subjects with asymptomatic brain metastasis without tumor-related brain edema, displacement, steroids or antiepileptic drugs can be enrolled.
• Subjects with meningitis or meningeal metastasis need to be excluded.
• People with bleeding or thromboembolism tendency:
• Have clinically significant bleeding symptoms or obvious bleeding tendency within 2 weeks before the study;

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Central Study Contacts

Zi B Wang

CONTACT

+8637165588219; zlyywzb2118@zzu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: June 30, 2024
• First Posted: August 9, 2024
• Study Start: August 1, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: August 9, 2024

Record last verified: 2024-06

Locations

CN (1)