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

ConditionsHPV-Associated Cervical CarcinomaHPV-Related CarcinomaHPV-Related MalignancyHPV Positive Oropharyngeal Squamous Cell CarcinomaHPV-Related AdenocarcinomaHPV-Related Adenosquamous CarcinomaHPV-Related Squamous Cell CarcinomaHPV-Related Anal Squamous Cell CarcinomaHPV-Related Penile Squamous Cell CarcinomaHPV-Related Vulvar Squamous Cell CarcinomaHPV-Related Endocervical AdenocarcinomaCervical CancerOropharynx CancerAnal CancerVulvar CancerPenile CancerVaginal Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorChristian Hinrichs

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Histologically confirmed carcinoma of a primary tumor site and stage indicated in Table 3 of the protocol.

Tumor with HPV16 genotype as determined by testing performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.

HLA-A*02:01 allele determined by testing performed in a CLIA certified laboratory. Participants may be enrolled based on low resolution typing (i.e., HLA-A*02) but the HLA-A*02:01 allele type must be confirmed prior to apheresis.

Measurable disease per RECIST Criteria Version 1.1 or PERCIST.

Disqualifiers

Have received prior systemic therapy or definitive chemoradiation for the cancer that is being treated on this protocol. Palliative radiation therapy for symptom management, such as to control tumor-induced bleeding, is permitted.

Current treatment with another investigational agent.

History of severe allergic reactions to compounds of similar chemical or biological composition to agents used in this study.

Uncontrolled intercurrent illness such as active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations at the time of treatment that would limit compliance with study requirements.

Trial design

Design model

Single group

Treatments tested in this trial

  • E7 TCR-T cells

    Biological/Vaccine

    Participants will receive a conditioning regimen consisting of cyclophosphamide and fludarabine. E7 TCR-T cells will be administered as a single intravenous infusion.

  • Aldesleukin

    Drug

    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.

Treatment groups

15 Participants
are divided into 1 treatment group
Group A: E7 TCR-T cellsExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Feasibility 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

Secondary outcomes

1

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

2-year and 5-year disease free survival (DFS)

DFS will be determined using the Kaplan-Meier method

Time frame
5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Christian Hinrichs

Lead sponsor

Rutgers, The State University of New Jersey

Sponsor institution

Iovance Biotherapeutics, Inc.

Collaborator

Source ClinicalTrials.gov
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