E7 TCR T Cells for Human Papillomavirus-Associated Cancers

February 13, 2026 updated by: Scott Norberg, D.O., National Cancer Institute (NCI)

A Phase I/II Trial of T Cell Receptor Gene Therapy Targeting HPV-16 E7 for HPV-Associated Cancers

Background:

Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have an HPV protein called E7 inside of their cells. In this new therapy, researchers take a person's blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 T cell receptor (TCR) cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people.

Objective:

To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients.

Eligibility:

Adults ages 18 and older with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal.

Design:

Participants will list all their medicines.

Participants will have many screening tests, including imaging procedures, heart and lung tests, and lab tests. They will have a large catheter inserted into a vein.

Participants will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.

The cells will be changed in the lab.

Participants will stay in the hospital. Over several days, they will get:

Chemotherapy drugs

E7 TCR cells

Shots or injections to stimulate the cells

Participants will be monitored in the hospital up to 12 days. They will get support medicine and have blood and lab tests.

Participants will have a clinic visit about 40 days after cell infusion. They will have a physical exam, blood work, scans, and maybe x-rays.

Participants will have many follow-up visits with the same procedures. At some visits, they may undergo leukapheresis.

Participants will be followed for 15 years.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background:

  • Metastatic or refractory/recurrent human papillomavirus (HPV)-16+ cancers (cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers) are incurable and poorly palliated by standard therapies.
  • HPV-16+ cancers constitutively express the HPV-16 E7 oncoprotein, which is absent from healthy human tissues.
  • Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies including HPV-16+ cancers.
  • T cells genetically engineered with a TCR targeting HPV-16 E7 (E7 TCR) display specific reactivity against human leukocyte antigen (HLA)-A2+, HPV-16+ target cells.

Objectives:

Phase I Primary Objective

- To determine a safe dose for E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers.

Phase II Primary Objective

-To determine safety and efficacy of E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers.

Eligibility:

  • Patients greater than or equal to 18 years old with metastatic or refractory/recurrent HPV-16+ cancer.
  • Prior first line systemic therapy is required unless the patient declines standard treatment.
  • Patients must be HLA-A*02:01-positive.

Design:

  • This is a phase I/II clinical trial that will test the safety and efficacy of E7 TCR cells.
  • All patients will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of E7 TCR cells. Cell infusion will be followed by high dose aldesleukin.
  • Re-enrollment will be allowed for a small number of subjects.

Study Type

Interventional

Enrollment (Actual)

224

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Rutgers Cancer Institute of New Jersey

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. Measurable metastatic or refractory/recurrent human papillomavirus (HPV-16+ cancer (determined by in situ hybridization (ISH) or a polymerase chain reaction (PCR)-based test).
    2. Patients must be human leukocyte antigen (HLA-A*02 by low resolution typing, and HLA-A*02:01 by one of the high-resolution type results.
    3. All patients must have received prior first line standard therapy or declined standard therapy.
    4. 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 with surgically resected brain metastases are eligible.
    5. Greater than or equal to 18 years of age.
    6. Able to understand and sign the Informed Consent Document.
    7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
    8. Individuals must be willing to practice birth control from the time of enrollment on this study up to twelve (12) months after treatment. Individuals must be willing to undergo testing for HPV-16 prior to becoming pregnant after this period.
    9. Individuals of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. Individuals of childbearing potential are defined as all individuals except individuals who are postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as individuals over the age of 55 who have not had a menstrual period in at least one year. Because there is a potential risk for adverse events in nursing infant's secondary to treatment of the mother with E7 T cell receptor (TCR) transduced peripheral blood lymphocytes (PBLs), breastfeeding should be discontinued if the individual is treated with E7 TCR transduced PBL. These potential risks may also apply to other agents used in this study.
    10. Serology:
  • Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)

  • Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative.

    a. Hematology:

  • Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
  • White blood count (WBC) greater than or equal to 3000/mm^3
  • Platelet count greater than or equal to 100,000/mm^3

  • Hemoglobin > 8.0 g/dL

    b. Chemistry:

  • Serum Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal
  • Calculated creatinine clearance (CCr) greater than or equal to 50 mL/min/1.73^2 using the Cockcroft-Gault equation

  • Total bilirubin less than or equal to 1.5 mg/dL, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL

    c. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the E7 TCR cells.

Note: Patients may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to Grade 1 or less.

EXCLUSION CRITERIA:

  1. Active systemic infections (for e.g.: requiring anti-infective treatment), coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, severe obstructive or restrictive pulmonary disease. Patients with abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible.
  2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  3. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
  4. Patients with autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis or pancreatitis, and systemic lupus erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not exclusionary.

  5. Patients on immunosuppressive drugs including corticosteroids. With the exception of: intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)

    -Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent;

    or,

    -Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication)

  6. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine or aldesleukin.
  7. Patients with a history of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test.

  8. Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested. The following patients will undergo cardiac evaluations

    1. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or
    2. Age greater than or equal to 50 years old
  9. Any other condition, which would, in the opinion of the Principal Investigator, indicate that the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained.
  10. Subjects with baseline screening pulse oxygen level of < 95% on room air will not be eligible. If the underlying cause of hypoxia improves, then they may be reevaluated

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1: Phase I
Non-myeloablative, lymphocyte depleting preparative regimen, followed by E7 T cell receptor (TCR) Cells at escalating doses, followed by aldesleukin.
Drug: Fludarabine
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Other Names:
  • Fludara
Drug: Cyclophosphamide
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Other Names:
  • Cytoxan
  • Neosar
Biological: E7 TCR cells
T cells genetically engineered with a T cell receptor (TCR) targeting human papillomavirus (HPV -16 E7 (E7 TCR) that display specific reactivity against human leukocyte antigen (HLA-A2+, HPV-16+ target cells.
Other Names:
  • E7 T Cell Receptor (TCR) cells
Drug: Aldesleukin
Following cell infusion, the patient receives high-dose bolus aldesleukin, which is dosed to individual patient tolerance. Aldesleukin improves the survival of E7 T cell receptor (TCR) cells after infusion.
Other Names:
  • Proleukin
  • IL-2
  • Interleukin-2
Diagnostic test: EKG
Screening/Baseline. Follow-up (end of treatment).
Other Names:
  • Electrocardiogram
Procedure: Biopsy
Screening/Baseline. Following treatment (6 weeks post treatment preferred) and at disease progression only.
Other Names:
  • Bx
Diagnostic test: Chest CT and MRI or PET
Screening/Baseline. Follow-up (end of treatment). 40 days (+/- 2 weeks) after cell infusion; additional visits as indicated.
Other Names:
  • Chest computed tomography and magnetic resonance imaging and positron emission tomography
Diagnostic test: PFT
Screening/Baseline.
Other Names:
  • Pulmonary function test
Drug: Granisetron
Supportive medication for nausea/vomiting/anorexia. 0.01 mg/kg intravenous (IV) every(q) day as needed (prn).
Other Names:
  • Sancuso
  • Kytril
  • Sustol
Drug: Ondansetron
Supportive medication for nausea/vomiting/anorexia. Ondansetron 10mg intravenous (IV) every(q) 8 hours(hr) as needed (prn).
Other Names:
  • Zofran
Drug: Droperidol
Supportive medication for nausea/vomiting/anorexia. 1mg intravenous (IV) at 4-6 hours(h) as needed (prn).
Other Names:
  • Inapsine
  • Droleptan
  • Dridol
  • Xomolix
  • Innovar
Drug: Prochlorperazine
Supportive medication for nausea/vomiting/anorexia. 25mg per rectum (PR) as needed (prn) or 10mg intravenous (IV) every(q) 6hours(h) prn.
Other Names:
  • Compazine
Drug: Diphenoxylate HCL
Supportive medication for diarrhea. 2.5mg by mouth (po) every(q) 3 hours(h) as needed (prn).
Other Names:
  • Diphenoxylate Hydrochloride
Drug: Atropine sulfate
Supportive medication for diarrhea. 25mcg by mouth (po) every(q) 3 hours(h) as needed (prn).
Other Names:
  • Atropen
Drug: Codeine sulfate
Supportive medication for diarrhea. 30-60mg by mouth (po) every(q) 4 hours(h) as needed (prn).
Other Names:
  • Codeine
Drug: Loperamide
Supportive medication for diarrhea. 2mg by mouth (po) every(q) 3 hours(h) as needed (prn).
Other Names:
  • Imodium A-D
Drug: Indomethacin
Supportive medication for fever. 50-75mg by mouth (po) every(q) 8 hours(h).
Other Names:
  • Indocin
  • Tivorbex
Drug: Acetaminophen
Supportive medication for fever. 650mg by mouth (po) every 4 hours (q) 4hr.
Other Names:
  • Tylenol
Drug: Diphenhydramine HCL
Supportive medication for pruritis. 25-50mg by mouth (po) every 4 hours (q) 4hr as needed (prn).
Other Names:
  • Benadryl
  • Unisom
  • Diphenhydramine Hydrochloride
  • ZzzQuil
Drug: Hydroxyzine HCL
Supportive medication for pruritis. 10-20mg by mouth (po) every 6 hours(h), as needed (prn).
Other Names:
  • Atarax
Drug: Meperidine
Supportive medication for chills. 25-50mg intravenous (IV) every 1 hour (q1hr), as needed (prn).
Other Names:
  • Demerol
Experimental: Arm 2: Phase II
1 x 10^e11 E7 Cells that was determined in Phase I + aldesleukin.
Drug: Fludarabine
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Other Names:
  • Fludara
Drug: Cyclophosphamide
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Other Names:
  • Cytoxan
  • Neosar
Biological: E7 TCR cells
T cells genetically engineered with a T cell receptor (TCR) targeting human papillomavirus (HPV -16 E7 (E7 TCR) that display specific reactivity against human leukocyte antigen (HLA-A2+, HPV-16+ target cells.
Other Names:
  • E7 T Cell Receptor (TCR) cells
Drug: Aldesleukin
Following cell infusion, the patient receives high-dose bolus aldesleukin, which is dosed to individual patient tolerance. Aldesleukin improves the survival of E7 T cell receptor (TCR) cells after infusion.
Other Names:
  • Proleukin
  • IL-2
  • Interleukin-2
Diagnostic test: EKG
Screening/Baseline. Follow-up (end of treatment).
Other Names:
  • Electrocardiogram
Procedure: Biopsy
Screening/Baseline. Following treatment (6 weeks post treatment preferred) and at disease progression only.
Other Names:
  • Bx
Diagnostic test: Chest CT and MRI or PET
Screening/Baseline. Follow-up (end of treatment). 40 days (+/- 2 weeks) after cell infusion; additional visits as indicated.
Other Names:
  • Chest computed tomography and magnetic resonance imaging and positron emission tomography
Diagnostic test: PFT
Screening/Baseline.
Other Names:
  • Pulmonary function test
Drug: Granisetron
Supportive medication for nausea/vomiting/anorexia. 0.01 mg/kg intravenous (IV) every(q) day as needed (prn).
Other Names:
  • Sancuso
  • Kytril
  • Sustol
Drug: Ondansetron
Supportive medication for nausea/vomiting/anorexia. Ondansetron 10mg intravenous (IV) every(q) 8 hours(hr) as needed (prn).
Other Names:
  • Zofran
Drug: Droperidol
Supportive medication for nausea/vomiting/anorexia. 1mg intravenous (IV) at 4-6 hours(h) as needed (prn).
Other Names:
  • Inapsine
  • Droleptan
  • Dridol
  • Xomolix
  • Innovar
Drug: Prochlorperazine
Supportive medication for nausea/vomiting/anorexia. 25mg per rectum (PR) as needed (prn) or 10mg intravenous (IV) every(q) 6hours(h) prn.
Other Names:
  • Compazine
Drug: Diphenoxylate HCL
Supportive medication for diarrhea. 2.5mg by mouth (po) every(q) 3 hours(h) as needed (prn).
Other Names:
  • Diphenoxylate Hydrochloride
Drug: Atropine sulfate
Supportive medication for diarrhea. 25mcg by mouth (po) every(q) 3 hours(h) as needed (prn).
Other Names:
  • Atropen
Drug: Codeine sulfate
Supportive medication for diarrhea. 30-60mg by mouth (po) every(q) 4 hours(h) as needed (prn).
Other Names:
  • Codeine
Drug: Loperamide
Supportive medication for diarrhea. 2mg by mouth (po) every(q) 3 hours(h) as needed (prn).
Other Names:
  • Imodium A-D
Drug: Indomethacin
Supportive medication for fever. 50-75mg by mouth (po) every(q) 8 hours(h).
Other Names:
  • Indocin
  • Tivorbex
Drug: Acetaminophen
Supportive medication for fever. 650mg by mouth (po) every 4 hours (q) 4hr.
Other Names:
  • Tylenol
Drug: Diphenhydramine HCL
Supportive medication for pruritis. 25-50mg by mouth (po) every 4 hours (q) 4hr as needed (prn).
Other Names:
  • Benadryl
  • Unisom
  • Diphenhydramine Hydrochloride
  • ZzzQuil
Drug: Hydroxyzine HCL
Supportive medication for pruritis. 10-20mg by mouth (po) every 6 hours(h), as needed (prn).
Other Names:
  • Atarax
Drug: Meperidine
Supportive medication for chills. 25-50mg intravenous (IV) every 1 hour (q1hr), as needed (prn).
Other Names:
  • Demerol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase II: Overall Response Rate Partial Response + Complete Response (PR +CR)
Time Frame: At 12 weeks, every 3 months x 3, and every 6 months for approximately 5 years
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Compete Response is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
At 12 weeks, every 3 months x 3, and every 6 months for approximately 5 years
Phase I: Number of Dose Limiting Toxicities (DLT)
Time Frame: From the day of cell infusion (Day 0) to Day +30
Adverse events were assessed by the Common Terminology Criteria for Adverse Events v4.0. Grade 3 is serious. Grade 4 is life-threatening. Grade 5 is death related to adverse event. A DLT is defined as all Grade 3 and greater toxicities occurring within 30 days of the cell infusion with the exception of: Cytokine Release Syndrome (CRS) that resolves ≤ grade 2 within 14 days of the last dose of aldesleukin. Autoimmune toxicity that resolves to ≤ grade 2 within 14 days for starting symptom treatment (e.g. steroids). Cardiac, gastrointestinal, dermatological, hepatic, pulmonary, renal, hematologic, neurologic toxicity, or toxicity in Appendix C of the protocol attributable to aldesleukin that resolves to ≤ grade 2 within 14 days of the last dose of aldesleukin. Transient grade 3 hypoxia associated with cell infusion that corrects to ≤ grade 2 with supplemental oxygen and/or that resolves to ≤ grade 2 within 24 hours or before starting aldesleukin.
From the day of cell infusion (Day 0) to Day +30

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: From the time of cell infusion (Day 0) until documented progressive disease; a maximum of 12 months
Progression-free survival is the time from start of treatment to disease progression or death from any cause. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Disease progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.
From the time of cell infusion (Day 0) until documented progressive disease; a maximum of 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
Time Frame: Adverse Events were monitored/assessed from the first study intervention, Study Day 0, through 40 days after the study therapy was last administered up to a maximum of 12 months
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Adverse Events were monitored/assessed from the first study intervention, Study Day 0, through 40 days after the study therapy was last administered up to a maximum of 12 months

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Scott M Norberg, D.O., National Cancer Institute (NCI)

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

Helpful Links

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)

January 27, 2017

Primary Completion (Actual)

July 2, 2025

Study Completion (Actual)

July 2, 2025

Study Registration Dates

First Submitted

August 4, 2016

First Submitted That Met QC Criteria

August 4, 2016

First Posted (Estimated)

August 8, 2016

Study Record Updates

Last Update Posted (Actual)

March 9, 2026

Last Update Submitted That Met QC Criteria

February 13, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 160154
  • 16-C-0154

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

IPD Sharing Time Frame

Clinical data available during the study and indefinitely.

IPD Sharing Access Criteria

Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

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.

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