E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers
A Phase II Trial of T Cell Receptor Gene Therapy Targeting Human Papillomavirus ( HPV) 16 E7 for HPV-Associated Cancers
4 other identifiers
interventional
20
1 country
3
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2023
Typical duration for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 25, 2022
CompletedFirst Posted
Study publicly available on registry
January 17, 2023
CompletedStudy Start
First participant enrolled
March 7, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 1, 2027
June 12, 2026
June 1, 2026
3.8 years
December 25, 2022
June 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Tumor response
Objective tumor response as measured by RECIST
5 years
Secondary Outcomes (1)
Adverse Events
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 every eight hours will be administered for up to six 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 or cytologically confirmed metastatic or refractory/recurrent HPV-16+ cancer.
- Tumor and/or blood with HPV16 genotype as determined by testing performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
- HLA-A\*02:01 allele as 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 as assessed by RECIST Criteria Version 1.1.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at screening.
- Must have received prior first line standard therapy or have declined standard therapy.
- Standard treatment options for first and second-line therapy must be presented and formally declined (Appendix VII).
- 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.
- 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 antigen (HBsAg), 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.
- Participants must have organ and marrow function as defined below:
- Leukocytes \> 3,000/mcL
- Absolute neutrophil count \> 1,500/mcL
- +10 more criteria
You may not qualify if:
- 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.
- History of severe allergic reactions to compounds of similar chemical or biological composition to agents used in this study.
- History of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test.
- 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, then they may be reevaluated.
- Subjects with HLA-A\*02:01 damaging mutation or allele loss detected by clinical or research genomic profiling will not be eligible.
- 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
- Cutaneous skin cancers requiring only local excision
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Christian Hinrichslead
- Iovance Biotherapeutics, Inc.collaborator
- National Cancer Institute (NCI)collaborator
Study Sites (3)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
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 2
- 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
December 25, 2022
First Posted
January 17, 2023
Study Start
March 7, 2023
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
January 1, 2027
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).