TCR-engineered T Cells in NSCLC and HNSCC Patients (ACTengine) (ACTengine)
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|ClinicalTrials.gov Identifier: NCT03247309|
Recruitment Status : Recruiting
First Posted : August 11, 2017
Last Update Posted : September 27, 2017
This clinical research study investigates IMA201 which is composed of special immune cells (T cells, also called T lymphocytes) being genetically modified by introduction of a tumor-antigen specific T cell receptor (TCR) to fight against cancer. Patients that choose to take part in this study have advanced cancer where there is no (further) standard treatment for their cancer available OR current treatments are not tolerated.
The main purpose of this clinical research study is to confirm the safety of IMA201 and to define the highest safe dose of IMA201 cells to give to patients. The study will also investigate what the specific side effects of this treatment are, and to see whether this therapy shows clinical activity in patients with their advanced cancer.
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor Cancer Head and Neck Squamous Cell Carcinoma Squamous Cell Non-small Cell Lung Cancer||Biological: IMA201 T-Cells Diagnostic Test: IMA201_Detect Diagnostic Test: ACT-HLA Drug: Fludarabine Drug: Cyclophosphamide Biological: Recombinant human interleukin-2||Phase 1|
SCREENING: First, the patient will have 2 sets of screening tests to determine eligibility: HLA (human leukocyte antigen) screening and Main screening. After both screenings are completed and if the patient is eligible, blood will be taken for the manufacture of IMA201.
The HLA screening test will be done by an investigational device. Patients must have the HLA-A*02:01 subtype to continue to the Main screening of the study. The Main screening will include medical tests and exams, including a tumor biopsy that will be tested for specific biomarkers by an investigational device called IMA201_Detect. Patients must be positive for at least one of the study's biomarkers to continue onto the leukapheresis part of the study.
Manufacturing phase: From the patient's blood collected at the leukapheresis, the investigators will make the IMA201 TCR-engineered T cells. In order to insert the new gene into the patient's T-cells, investigators will use a gene transfer technology. This will be done with a lentiviral vector derived from a virus. The vector was made specifically for this study and will carry the TCR genes into the T cells.
TREATMENT: In other clinical studies using T cells, some investigators found that giving chemotherapy before the T cell infusion can improve the amount of time the T cells stay in the body. Giving chemotherapy before a T cell infusion is called lymphodepletion. The chemotherapy used for lymphodepletion in this study will be a combination of cyclophosphamide and fludarabine which would be given in the days before the IMA201 T cell infusion. Two days after the last chemotherapy dose, the patient will be admitted to the hospital the night before the IMA201 infusion. The IMA201 treatment will be given at MD Anderson Cancer Center.
After IMA201 infusion, a low dose of IL-2 will be given twice daily for a period of time.
Since this study involves gene therapy, patients will be monitored throughout the study and for up to a total of 15 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||16 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Trial Evaluating Genetically Modified Autologous T Cells Expressing a T-Cell Receptor Recognizing a Cancer/Germline Antigen in Patients With Squamous Cell Non-small Cell Lung Cancer or Head and Neck Squamous Cell Carcinoma|
|Actual Study Start Date :||September 26, 2017|
|Estimated Primary Completion Date :||December 31, 2018|
|Estimated Study Completion Date :||December 31, 2033|
Experimental: IMA201 T-Cells
Biological: IMA201 T-Cells
The cell dose will be based on viable CD3+CD8+ HLA-Dextramer+ cells per body surface area (BSA) as defined by the Mosteller formula.Diagnostic Test: IMA201_Detect
IMA201_Detect is developed as a companion diagnostic to aid in selecting patients with relapsed and/or refractory solid cancers who might be eligible for enrollment in clinical trials with investigational IMA201 T-Cell therapy. IMA201_Detect is intended for investigational use only.Diagnostic Test: ACT-HLA
An assay used to determine whether a patient is positive for the allele HLA-A*02:01 or not, and thus is eligible for treatment with an ACTengine adoptive T-cell product.Drug: Fludarabine
Other Name: Fludarabine MonophosphateDrug: Cyclophosphamide
Other Name: CytoxanBiological: Recombinant human interleukin-2
Low dose IL-2 Infusion for two weeks
- Incidence of adverse events (AE) [ Time Frame: up to 15 years post-treatment ]During treatment and treatment observation phases and long term gene safety follow up, AE and SAE will be captured per CTCAE v4.0. AEs and SAEs will be summarized.
- Duration of infused T cells over time (Persistence of T cells) [ Time Frame: Up to 12 months ]Blood samples will be collected at selected time points (pre- and post-IMA201 treatment at set time points) to assess the persistence of IMA201 T-cells in the blood.
- Incidence of infused T cells (Functionality of T cells) [ Time Frame: Up to 12 months ]
- Success Rates of T cell generation (Feasibility of ACTengine approach) [ Time Frame: This endpoint can be evaluated after production of the last patient's specific T-cell product, i.e. after release of the last patient's cell product. Approximately 10 months ]
- Number of subjects with Clinical response [ Time Frame: 12 weeks and 24 weeks post IMA201 infusion ]
- Levels of Blood biomarkers [ Time Frame: until the end of the trial, up to 15 years from last patient treatment ]
- Levels of Tumor biomarkers [ Time Frame: until the end of the trial, up to 15 years from last patient treatment ]
- Rate of successful biomarker tests for tumor samples collected [ Time Frame: This can be evaluated after last patient's enrollment, approximately 12 months ]
- Percentages of patients expressing individual targets [ Time Frame: This can be evaluated after last patient's enrollment, approximately 10 months after start of trial. ]
- Concordance of HLA-A*02:01 Determination assay [ Time Frame: This can be evaluated after last patient's enrollment, approximately 10 months after start of trial. ]
- Overall Survival (OS) will be assessed. [ Time Frame: until the end of the trial, up to 15 years from last patient treatment. ]
- Progression Free Survival (PFS) will be assessed. [ Time Frame: until the end of the trial, up to 15 years from last patient treatment. ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03247309
|Contact: Hong Ma, M.D.||firstname.lastname@example.org|
|Contact: George R Blumenschein, Jr., M.D.||email@example.com|
|United States, Texas|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Study Director:||Hong Ma, M.D.||Immatics US, Inc.|
|Principal Investigator:||George R Blumenschein, Jr., M.D.||MDACC|