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
2 other identifiers
interventional
15
1 country
2
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Aug 2025
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 28, 2022
CompletedFirst Posted
Study publicly available on registry
December 7, 2022
CompletedStudy Start
First participant enrolled
August 11, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2026
June 12, 2026
June 1, 2026
1.1 years
November 28, 2022
June 10, 2026
Conditions
Keywords
Outcome Measures
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
6 weeks
Secondary Outcomes (2)
Objective tumor response rate at 6-weeks after treatment
6 weeks
2-year and 5-year disease free survival (DFS)
5 years
Study Arms (1)
E7 TCR-T cells
EXPERIMENTALSubjects will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
- Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy test is not required for women who have had a bilateral oophorectomy or hysterectomy.
- Men and women of child-bearing potential must agree to use adequate contraception (i.e., intrauterine device, hormonal barrier method of birth control, abstinence, tubal ligation, or vasectomy) prior to study entry and for four months after treatment. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
- Seronegative for HIV antibody, hepatitis B surface antigen (HBsAg), and hepatitis C antibody. If a hepatitis C antibody test is positive, then testing for antigen by reverse transcription polymerase chain reaction (RT-PCR) must be negative.
- Participants must have organ and marrow function as defined below:
- Leukocytes \> 3,000/mcL
- Absolute neutrophil count \> 1,500/mcL
- Platelets \> 100,000/mcL
- Hemoglobin \> 9.0 g/dL
- Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin \< 3.0 mg/dL.
- +6 more criteria
You may not qualify if:
- 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.
- Subjects with HLA-A\*02:01 damaging mutation or allele loss detected by research or clinical sequencing will not be eligible.
- Documented LVEF of less than or equal to 45% tested. The following participants will undergo cardiac evaluations:
- Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or
- Age ≥ 50 years old
- Participants with baseline screening pulse oxygen level of ≤ 92% on room air will not be eligible. If the underlying cause of hypoxia improves, they may be reevaluated.
- Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be discontinued if the mother is treated with E7 TCR T cells. These potential risks may also apply to other agents used in this study.
- Participants with a systemic immunodeficiency including acquired deficiency such as HIV or primary immunodeficiency such as Severe Combined Immunodeficiency Disease are ineligible. The experimental treatment being evaluated in this protocol depends on an intact immune system. Participants who have decreased immune competence may be less responsive to the treatment.
- Participants on immunosuppressive drugs including corticosteroids unless meeting criteria outlined in Section 6.1 (Prohibited Medications).
- Participants with potentially severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor autoimmune disorders are eligible.
- Participants with prior or concurrent malignancy whose natural history or treatment is unlikely to interfere with the safety or efficacy assessments of the investigational regimen are eligible for this trial. Examples include, but are not limited to:
- Carcinoma in situ
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Christian Hinrichslead
- Iovance Biotherapeutics, Inc.collaborator
Study Sites (2)
Rutgers Cancer Institute
New Brunswick, New Jersey, 08901, United States
RWJBarnabas Health - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08901, United States
Related Publications (1)
Nagarsheth NB, Norberg SM, Sinkoe AL, Adhikary S, Meyer TJ, Lack JB, Warner AC, Schweitzer C, Doran SL, Korrapati S, Stevanovic S, Trimble CL, Kanakry JA, Bagheri MH, Ferraro E, Astrow SH, Bot A, Faquin WC, Stroncek D, Gkitsas N, Highfill S, Hinrichs CS. TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers. Nat Med. 2021 Mar;27(3):419-425. doi: 10.1038/s41591-020-01225-1. Epub 2021 Feb 8.
PMID: 33558725BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christian S Hinrichs, MD
Rutgers Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Chief, Section of Cancer Immunotherapy
Study Record Dates
First Submitted
November 28, 2022
First Posted
December 7, 2022
Study Start
August 11, 2025
Primary Completion (Estimated)
October 1, 2026
Study Completion (Estimated)
October 1, 2026
Last Updated
June 12, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- SAP
- Time Frame
- Data will be made available through the publisher at the time of publication.
- Access Criteria
- Data will be accessible through the publisher.
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).