Phase I Study of HER2 Chimeric Antigen Receptor (CAR) T Cells in Combination With Checkpoint Blockade in Patients With Advanced Sarcoma (HEROS 3.0)
Baylor College of Medicine
Summary
The purpose of this study is to learn whether it is safe to give HER2-CAR T cells in combination with an immune checkpoint inhibitor drug (pembrolizumab or nivolumab), to learn what the side effects are, and to see whether this therapy might help patients with sarcoma. Another goal of this study is to study the bacteria found in the stool of patients with sarcoma who are being treated with HER2 CAR T cells and immune checkpoint inhibitor drugs to see if the types of bacteria influence how well the treatment works. The investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. They now want to see if they can put a new gene in these cells that will let the T cells recognize and kill sarcoma cells. The new gene that the investigators will put in makes an antibody specific for HER2 (Human Epidermal Growth Factor Receptor 2) that binds to sarcoma cells. In addition, it contains CD28, which stimulated T cells and make them last longer. After this new gene is put into the T cell, the T cell becomes known as a chimeric antigen receptor T cell or CAR T cell. In another clinical study using these CAR T cells targeting HER2 as well as other studies using CAR T cells, investigators found that giving chemotherapy before the T cell infusion can improve the effect the T cells can have. Giving chemotherapy before a T cell infusion is called lymphodepletion since the chemotherapy is specifically chosen to decrease the number of lymphocytes in the body. Decreasing the number of the patient's lymphocytes first should allow the infused T cells to expand in the body, and potentially kill cancer cells more effectively. The chemotherapy used for lymphodepletion is a combination of cyclophosphamide and fludarabine. After the patient receives the lymphodepletion chemotherapy and CAR T cells during treatment on the study, they will receive an antibody drug called an immune checkpoint inhibitor, pembrolizumab or nivolumab. Immune checkpoint inhibitors are drugs that remove the brakes on the immune system to allow it to act against cancer.
Description
Patients will first be asked to give blood to make the HER2 CAR T cells. These cells are grown and frozen for the patient. To get the HER2 antibody (and the CD28zeta) to attach to the surface of the T-cell, investigators insert the antibody gene into the T-cell. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps the investigators find the T cells in the patient's blood after they are injected. Because the patients in this study receive cells with a new gene in them, they will be followed for a…
Eligibility
- Age range
- 1–25 years
- Sex
- All
- Healthy volunteers
- No
Procurement Inclusion Criteria: * Diagnosis of a HER2-positive sarcoma. Immunohistochemistry (IHC) will be used to determine HER2 expression. Standard HER2 positive breast cancer density gradient tissue microarrays will be used as positive controls. HER2 expression will be graded for percent positive tumor cells (Grade 0: no staining; Grade 1: 1-25%; Grade 2: 26-50% and Grade 3: 51-100%) and intensity of staining (Negative; 1+; 2+; and 3+). For the patient to meet eligibility, tumors are required to have at least ≥ grade 1 and ≥ 1+ intensity score for HER2 staining. * Age between 1 to 25 year…
Interventions
- GeneticT cells or CAR T cells
There are 2 dose levels: Dose Level 1 (1x10\^8 cells/m2) and Dose Level -1 (5x10\^7 cells/m2). In the event that Dose Level 1 is not tolerable, de-escalation to Dose Level -1 will occur.
- DrugPembrolizumab Injectable Product
2 mg/kg/dose (max 200 mg/dose) every 3 weeks
- DrugNivolumab Injectable Product
3 mg/kg/dose (\<40kg) or 124 mg (≥40 kg) every 2 weeks
Location
- Texas Children's HospitalHouston, Texas