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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05686226
Recruitment Status : Recruiting
First Posted : January 17, 2023
Last Update Posted : October 12, 2023
Sponsor:
Information provided by (Responsible Party):
Christian Hinrichs, Rutgers, The State University of New Jersey

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cervical Cancer Throat Cancer Oropharynx Cancer Anal Cancer Vulva Cancer Vaginal Cancer Penile Cancer Metastatic Cancer HPV-Related Malignancy HPV-Related Carcinoma HPV-Related Cervical Carcinoma HPV-Related Squamous Cell Carcinoma HPV-Related Adenocarcinoma HPV Positive Oropharyngeal Squamous Cell Carcinoma HPV-Associated Vaginal Adenocarcinoma HPV-Related Adenosquamous Carcinoma HPV-Related Endocervical Adenocarcinoma HPV-Related Anal Squamous Cell Carcinoma HPV-Related Penile Squamous Cell Carcinoma HPV-Related Vulvar Squamous Cell Carcinoma HPV Positive Rectal Squamous Cell Carcinoma Biological: E7 TCR-T cells Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single-arm phase II clinical trial.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of T Cell Receptor Gene Therapy Targeting Human Papillomavirus ( HPV) 16 E7 for HPV-Associated Cancers
Actual Study Start Date : March 7, 2023
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. Tumor response [ Time Frame: Five years ]
    Objective tumor response as measured by RECIST


Secondary Outcome Measures :
  1. Adverse Events [ Time Frame: 5 years ]
    Adverse events as measured by CTCAE


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05686226


Contacts
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Contact: Carrie Snyder 732-235-7356 cs1449@cinj.rutgers.edu

Locations
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United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Carrie Snyder    732-235-7356    cs1449@cinj.rutgers.edu   
RWJBarnabas Health - Robert Wood Johnson University Hospital Not yet recruiting
New Brunswick, New Jersey, United States, 08901
Contact: Carrie Snyder    732-235-7356    cs1449@cinj.rutgers.edu   
Sponsors and Collaborators
Christian Hinrichs
Investigators
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Principal Investigator: Christian Hinrichs, MD Rutgers Cancer Institute of New Jersey
More Information
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Publications:

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Responsible Party: Christian Hinrichs, Chief, Section of Cancer Immunotherapy, Rutgers, The State University of New Jersey
ClinicalTrials.gov Identifier: NCT05686226    
Other Study ID Numbers: 192204
Pro2022002259 ( Other Identifier: Rutgers, The State University of New Jersey )
First Posted: January 17, 2023    Key Record Dates
Last Update Posted: October 12, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Primary and secondary endpoint data will be shared.
Supporting Materials: Statistical Analysis Plan (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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Christian Hinrichs, Rutgers, The State University of New Jersey:
Chimeric antigen receptors (CAR-T)
Tumor infiltrating lymphocyte
TCR-T
immunotherapy
T cell
adoptive cell therapy
cellular therapy
gene therapy
human papillomavirus
HPV
E7
T cell receptor
 TCR
E7 TCR
lymphocyte
cell therapy
cervical cancer
oropharyngeal cancer
anal cancer
vulvar cancer
vaginal cancer
penile cancer
tumor infiltrating lymphocytes (TIL)
TIL therapy
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Uterine Cervical Neoplasms
Anus Neoplasms
Squamous Cell Carcinoma of Head and Neck
Vaginal Neoplasms
Oropharyngeal Neoplasms
Penile Neoplasms
Carcinoma, Adenosquamous
Vulvar Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
 Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Diseases
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms