This phase I/II trial investigates the side effects of genetically engineered cells called FH-MagIC TCR-T cells and how well they work with atezolizumab in treating patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer that has spread to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize MAGE-A1, a protein on the surface of tumor cells. These MAGE-A1-specific T cells may help the body's immune system identify and kill MAGE-A1 tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving FH-MagIC TCR-T cells with atezolizumab may help treat patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer.
OUTLINE: This is a phase I, dose escalation study of FH-MagIC TCR-T cells followed by a phase II study. LYMPHODEPLETION: Patients receive cyclophosphamide intravenously (IV) and fludarabine IV on days -4, -3, and -2 before each T-cell infusion. T-CELL INFUSION: Patients receive FH-MagIC TCR-T cells IV over 15-20 minutes. Six to twelve weeks after first T-cell infusion, patients with progressive disease and non-persisting transgenic TCR T cells may receive a second T-cell infusion. In the Phase 2 portion of the study, atezolizumab will be administered as standard of care beginning 24-72 hours after T-cell infusion. Atezolizumab will be given IV every 3 weeks for at least 1 year in the absence of disease progression or unacceptable toxicity. An alternative PD1 inhibitor may be substituted if atezolizumab (preferred) is not available. After completion of study treatment, patients are followed up annually for 15 years after final infusion of FH-MagIC TCR-T.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Given IV
Given IV
Given IV
Given IV
Given IV
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Count of Participants That Experienced Treatment-related Unexpected Grade 3 or Higher Adverse Events
Time frame: 4 weeks post last infusion per patient
Best Overall Response
Lesions will be separately tracked but response determined in totality. As indicated, patient must have at least one trackable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Response will be a defined as best overall response by RECIST 1.1. A Complete Response will be defined as total regression of all tumors, a Partial Response as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and Progressive Disease as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter. If the disease does not fall in either category it will be considered Stable Disease (RECIST v1.1 criteria).
Time frame: 1 year post infusion
Peripheral Blood Concentration of Infused Transgenic T Cells Over Time
Results will be reported by sample for the single treated patient. Patient samples were tested using a WPRE assay showing transgenic T cells in blood. This was detected by qPCR.
Time frame: 1 year post infusion
Participants That Displayed Transgenic T Cells in Tumor Tissue
Outcome will be reported as a count of participants that displayed transgenic T cells in their tumor tissue after treatment. This was assessed by WRPE staining and scRNA sequencing. Unfortunately, no transgenic cells were detected on the one treated patient's tumors.
Time frame: 1 year post infusion
Progression-free Survival
Outcome will be reported as a count of participants that were alive as the 1 year post infusion timepoint and also had not experienced progression at that timepoint.
Time frame: 1 year post infusion
Overall Survival
Outcome will be reported as a count of participants that were alive at the 1 year post infusion timepoint.
Time frame: 1 year post infusion
Objective Response Rates
Evaluated by immune-related RECIST criteria. Outcome will be reported as a count of participants that experienced a Complete Response or Partial Response per RECIST criteria. A complete response (CR) will be defined as total regression of all tumors, a Partial Response as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and Progressive Disease as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter. If the disease does not fall in either category it will be considered Stable Disease (RECIST v1.1 criteria).
Time frame: 1 year post infusion
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.