NCT05639972

E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers

A Feasibility Study of E7 TCR-T Cell Induction Therapy for Locoregionally Advanced HPV-Associated Cancers

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: Christian Hinrichs · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• HPV-Associated Cervical Carcinoma
• HPV-Related Carcinoma
• HPV-Related Malignancy
• HPV Positive Oropharyngeal Squamous Cell Carcinoma
• HPV-Related Adenocarcinoma
• HPV-Related Adenosquamous Carcinoma
• HPV-Related Squamous Cell Carcinoma
• HPV-Related Anal Squamous Cell Carcinoma
• HPV-Related Penile Squamous Cell Carcinoma
• HPV-Related Vulvar Squamous Cell Carcinoma
• HPV-Related Endocervical Adenocarcinoma
• Cervical Cancer
• Oropharynx Cancer
• Anal Cancer
• Vulvar Cancer
• Penile Cancer
• Vaginal Cancer

Interventions

Type	Name	Description
BIOLOGICAL	E7 TCR-T cells	Participants will receive a conditioning regimen consisting of cyclophosphamide and fludarabine. E7 TCR-T cells will be administered as a single intravenous infusion.
DRUG	Aldesleukin	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.

Timeline

• Start date: 2025-08-11
• Primary completion: 2026-10-01
• Completion: 2026-10-01
• First posted: 2022-12-07
• Last updated: 2026-02-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study