E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers

October 10, 2023 updated by: Christian Hinrichs

A Phase II Trial of T Cell Receptor Gene Therapy Targeting Human Papillomavirus ( HPV) 16 E7 for HPV-Associated Cancers

This is a phase II clinical trial to assess the clinical activity of immunotherapy with E7 TCR-T cells for metastatic HPV-associated cancers. HPV-associated cancers in include cervical, throat, penile, vulvar, vaginal, anal, and other cancers. Participants will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin. Clinical response to treatment will be determined.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will determine the tumor response rate for the treatment of HPV-associated cancers with E7 TCR-T cells. E7 TCR-T cells are autologous gene-engineered T cells that target HPV16 E7 through a T cell receptor (TCR). E7 is an HPV oncoprotein that is present in HPV-associated cancers. Participants must have the HLA-A*02:01 allele, which is required for tumor targeting by the E7 TCR. Treatment consists of a conditioning regimen (cyclophosphamide and fludarabine), a single infusion of E7 TCR-T cells, and adjuvant aldesleukin. Tumor response rate and response duration will be determined. Safety data will also be collected.

Study Type

Interventional

Enrollment (Estimated)

20

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Contact:
      • New Brunswick, New Jersey, United States, 08901
        • Not yet recruiting
        • RWJBarnabas Health - Robert Wood Johnson University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically or cytologically confirmed metastatic or refractory/recurrent HPV-16+ cancer.
  2. Tumor with HPV16 genotype as determined by testing performed in a CLIA certified laboratory.
  3. HLA-A*02:01 allele as determined by testing performed in a Clinical Laboratory Improvement Amendments (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.
  4. Measurable disease as assessed by RECIST Criteria Version 1.114.
  5. Age ≥ 18 years.
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at screening.
  7. Must have received prior first line standard therapy or have declined standard therapy.
  8. Standard treatment options for first and second-line therapy must be presented and formally declined (Appendix VII).
  9. Patients with three or fewer brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. Patients must be fully recovered from surgery.
  10. Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy tests is not required for women who have had a bilateral oophorectomy or hysterectomy.
  11. 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 women become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
  12. Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody. If a hepatitis C antibody test is positive, then testing for antigen by RT-PCR for Hepatitis C (HCV) RNA must be negative.

  13. Participants must have organ and marrow function as defined below:

    1. Leukocytes > 3,000/microliter (mcL)
    2. Absolute neutrophil count > 1,500/mcL
    3. Platelets > 100,000/mcL
    4. Hemoglobin > 8.0 g/dL
    5. Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL.
    6. Serum aspartate transferase (AST) (SGOT)/alanine transaminase (ALT) (SGPT) < 2.5 x upper limit of normal (ULN)
    7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation).
    8. international normalized ratio (INR) or activated partial thromboplastin time ( aPTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy. Subjects on anticoagulant therapy must have a PT or aPTT within therapeutic range and no history of severe hemorrhage.
  14. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the E7 TCR cells.
  15. Participants must be able to understand and be willing to sign the written informed consent document.
  16. Participants must agree to participate in protocol Cancer Institute of New Jersey (CINJ) 192103 (Pro2021002307) for gene therapy long term follow up and in protocol CINJ 192002 (Pro2021000281) for biospecimen collection study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: E7 TCR-T cells
Subjects will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin.
Biological: E7 TCR-T cells
Participants will receive a conditioning regimen (cyclophosphamide and fludarabine), E7 TCR-T cells as a single infusion, and adjuvant high-dose aldesleukin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor response
Time Frame: Five years
Objective tumor response as measured by RECIST
Five years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 5 years
Adverse events as measured by CTCAE
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Christian Hinrichs

Investigators

  • Principal Investigator: Christian Hinrichs, MD, Rutgers Cancer Institute of New Jersey

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2023

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

December 25, 2022

First Submitted That Met QC Criteria

January 8, 2023

First Posted (Actual)

January 17, 2023

Study Record Updates

Last Update Posted (Actual)

October 12, 2023

Last Update Submitted That Met QC Criteria

October 10, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 192204
  • Pro2022002259 (Other Identifier: Rutgers, The State University of New Jersey)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Primary and secondary endpoint data will be shared.

IPD Sharing Time Frame

Data will be made available through the publisher at the time of publication.

IPD Sharing Access Criteria

Data will be accessible through the publisher.

IPD Sharing Supporting Information Type

  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cervical Cancer

Clinical Trials on E7 TCR-T cells

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Finland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe