KRAS G12VPhase 1NCT06545201
RE001 T Cell Injection for the Treatment of KRAS G12V Mutated Solid Tumors
A Phase 1 study testing RE001 T cell in people with KRAS G12V and T Cell Therapy, run by Henan Cancer Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- KRAS G12V, T Cell Therapy
- What is being tested?
- RE001 T cell
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2024to 1 Apr 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
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- 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);
- Prothrombin time international normalized ratio INR ≦ 1.5×upper limit of normal time, unless anticoagulant therapy was received;
- Partial prothrombin time (APTT) ≦ 1.5×upper limit of normal time, unless receiving antibiotics coagulation therapy;
- Serum creatinine ≦ 1.5mg/dL (or 132.6μmol/L);
- Aspartate aminotransferase (AST/SGOT) ≦ 2.5×ULN;
- Alanine aminotransferase (ALT/SGPT) ≦ 2.5×ULN;
- Total bilirubin (TBIL) ≦ 1.5×ULN;
- In patients with liver metastasis, aspartate aminotransferase and alanine aminotransferase need to be ≦ 5×ULN.
- 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;
- 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;
- During the entire trial period, you can regularly visit the participating research institutions for relevant testing, evaluation and management.
Who cannot join
- 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;
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- 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;
- Have inherited or acquired bleeding and thrombosis tendencies;
- A serious arterial/venous thromboembolic event within the past 6 months.
- Suffering from massive pericardial effusion or symptomatic thoracic or abdominal effusion;
- Have received live attenuated vaccines within 4 weeks before cell infusion, or plan to receive this type of vaccine during the study;
- History of organ allogeneic transplantation, allogeneic stem cell transplantation and renal replacement therapy;
- Uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure;
- Known alcohol and/or drug abusers;
- Pregnant or breastfeeding women;
- Have any coexisting medical conditions or diseases that the researcher determines may impair the conduct of this trial subjects;
- No legal capacity/restricted capacity;
- Have previously received any gene or cell therapy products.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: RE001 T Cell Injection for the Treatment of KRAS G12V Mutated Solid Tumors, an Open-label Single-center Phase I Clinical Trial
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.
Read the detailed description
This study is a single-center, open, single-arm, dose-increasing, single-dose phase I clinical trial of safety and tolerance. It is planned to recruit 30 patients with advanced malignant solid tumor with KRAS G12V mutation.
In this experiment, 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. At least 21 days before T cell infusion, peripheral blood mononuclear cell (PBMC) (about 1×10^9) of the subjects were collected by a single blood cell separator. After gene editing, these cells were amplified in vitro and infused into the subjects after reaching the target number. The evaluation period of dose-limited toxicity (DLT) was 28 days after the first administration of each dose group.
The subjects were administered at intervals, and the interval of administration began from the day of TCR-T cell infusion of the previous subject to the day of TCR-T cell infusion of the next subject. The interval between the first three subjects in the same dose group and the next subject (the same group or different groups) is at least 14 days; If one third of the subjects in the dose group have DLT, and three new subjects need to be added, the interval with the next subject (same group or different group) should be at least 21 days.
All the 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.
During the trial, the subjects can withdraw from the study at any time for any reason, which will not affect the subsequent treatment and care of the subjects by medical staff or medical institutions.
- Conditions
- KRAS G12V, T Cell Therapy
- Being tested
- RE001 T cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RE001 T cellBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: RE001 T cell |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall response rate (ORR).
Defined as the proportion of subjects with confirmed CR and PR.
Measured: 24-36 months
Secondary outcomes (1)
Duration of response (DOR).
Defined as the time from cell infusion to disease progression or death in subjects achieving CR or PR.
Measured: 24-36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2024
- Study start1 Aug 2024 (estimated)
- Primary completion1 Apr 2026 (estimated)
- Study completion1 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for KRAS G12VStudies of the same condition, open and under way.
- More trials run by Henan Cancer HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henan Cancer Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06545201
- Sponsor's protocol ID
- RE00120231204
- Status last verified
- Jun 2024
- First submitted
- 30 Jun 2024
- Last updated
- 9 Aug 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RE001 T Cell Injection for the Treatment of KRAS G12V Mutated Solid Tumors, an Open-label Single-center Phase I Clinical Trial
- ClinicalTrials.gov ID
- NCT06545201
- Acronym / sponsor ID
- RE00120231204
- Conditions
- KRAS G12V, T Cell Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Henan Cancer HospitalOther government
- Study start
- 1 Aug 2024 (estimated)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 1 Apr 2027 (estimated)
- First posted
- 9 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study is a single-center, open, single-arm, dose-increasing, single-dose phase I clinical trial of safety and tolerance. It is planned to recruit 30 patients with advanced malignant solid tumor with KRAS G12V mutation.
In this experiment, 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. At least 21 days before T cell infusion, peripheral blood mononuclear cell (PBMC) (about 1×10^9) of the subjects were collected by a single blood cell separator. After gene editing, these cells were amplified in vitro and infused into the subjects after reaching the target number. The evaluation period of dose-limited toxicity (DLT) was 28 days after the first administration of each dose group.
The subjects were administered at intervals, and the interval of administration began from the day of TCR-T cell infusion of the previous subject to the day of TCR-T cell infusion of the next subject. The interval between the first three subjects in the same dose group and the next subject (the same group or different groups) is at least 14 days; If one third of the subjects in the dose group have DLT, and three new subjects need to be added, the interval with the next subject (same group or different group) should be at least 21 days.
All the 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.
During the trial, the subjects can withdraw from the study at any time for any reason, which will not affect the subsequent treatment and care of the subjects by medical staff or medical institutions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RE001T cell adoptive immunotherapy | Experimental | Biological: RE001 T cell3+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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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;
Key exclusion criteria (26 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RE001 T cellAll 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. | Biological | RE001T cell adoptive immunotherapy |
Primary outcome
Overall response rate (ORR).
Time frame: 24-36 months
Defined as the proportion of subjects with confirmed CR and PR.
1 secondary outcome
Duration of response (DOR).
Time frame: 24-36 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RE001 T cell in people with KRAS G12V and T Cell Therapy, run by Henan Cancer Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zi B Wang (+8637165588219, zlyywzb2118@zzu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response rate (ORR). (time frame: 24-36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.