The goal of this study is to determine the feasibility of administration of a single dose of E7 TCR-T cells as induction therapy prior to definitive treatment (chemoradiation or surgery) of locoregionally advanced HPV-associated cancers. The intent of E7 TCR-T cell treatment is to shrink or eliminate tumors and thereby facilitate definitive therapy and increase overall survival. This study seeks to determine 1) if E7 TCR-T cells can be administered without undue delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, and 3) the disease-free survival rate at 2 and 5 years. Participants will undergo an apheresis procedure to obtain T cells that will be genetically engineered to generate E7 TCR-T cells. They will receive a conditioning regimen, a single infusion of their own E7 TCR-T cells, and adjuvant aldesleukin. Participants will follow up to assess safety and determine tumor response and will return to their primary oncology team for definitive therapy.
This is a single-arm, single-cohort, single-center, feasibility study to determine the feasibility of E7 TCR-T cell induction therapy for locoregionally advanced human papillomavirus (HPV)-associated cancers (LAHPVC). Participants must have LAHPVC with HPV-16-positive cancer (tumor test) and the human leukocyte antigens (HLA)-A\*02:01 allele (blood test). Participants will undergo apheresis for generation of autologous, gene-engineered, E7 TCR-T cells. One week after apheresis, they will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine. Conditioning will be followed by a single infusion of E7 TCR T cells and adjuvant high-dose aldesleukin. Participants will follow up 3 weeks and 6 weeks after treatment. Tumor response will be assessed by imaging studies at the 6-week time point. Participants will be referred back to their primary oncology team for definitive therapy after the 6-week assessment (or earlier if tumors do not appear to be responding). Participants will be followed to determine 2- and 5-year disease free survival.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Participants will receive a conditioning regimen consisting of cyclophosphamide and fludarabine. E7 TCR-T cells will be administered as a single intravenous infusion.
Within 24 hours after E7 TCR-T cell infusion, aldesleukin 720,000 IU/kg IV will be administered every 8 hours as an inpatient for up to 3 doses. Aldesleukin dosing will be stopped for aldesleukin-related grade 3 or greater toxicity other than flushing, fever, chills, or hemodynamic changes (tachycardia or hypotension) that respond to crystalloid infusion. Aldesleukin may also be stopped at any time at investigator discretion.
Rutgers Cancer Institute
New Brunswick, New Jersey, United States
RECRUITINGRWJBarnabas Health - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
RECRUITINGFeasibility of administering E7 TCR-T cell therapy as induction treatment for LAHPVC
Proportion of subjects who complete treatment without an event that meets criteria for feasibility failure
Time frame: 6 weeks
Objective tumor response rate at 6-weeks after treatment
Tumor response as assessed by imaging using Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1 or PERCIST
Time frame: 6 weeks
2-year and 5-year disease free survival (DFS)
DFS will be determined using the Kaplan-Meier method
Time frame: 5 years
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.