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Papillomavirus InfectionsPhase 1/2NCT02858310

E7 TCR T Cells for Human Papillomavirus-Associated Cancers

A Phase 1/2 study testing E7 TCR cells, Aldesleukin and Fludarabine in people with Papillomavirus Infections and Cervical Intraepithelial Neoplasia, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
E7 TCR cells, Aldesleukin and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
224 participants
Where
2 sitesUnited States
Study dates
27 Jan 2017to 2 Jul 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Measurable metastatic or refractory/recurrent human papillomavirus (HPV-16+ cancer (determined by in situ hybridization (ISH) or a polymerase chain reaction (PCR)-based test).
  • 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.
  • All patients must have received prior first line standard therapy or declined standard therapy.
  • 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.
  • Greater than or equal to 18 years of age.
  • Able to understand and sign the Informed Consent Document.
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  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
  • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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.

Who cannot join

  • 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.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  • 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).
  • 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.
  • 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;
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  • or,
  • -Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication)
  • History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine or aldesleukin.
  • Patients with a history of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test.
  • Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested. The following patients 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 greater than or equal to 50 years old
  • 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.
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

Other trials in United States

About this study

Official title: 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.

Read more

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.

Read the 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.
Being tested
E7 TCR cells, Aldesleukin, Fludarabine, Cyclophosphamide, EKG
Keywords
Immunotherapy, Human Papillomavirus, Vulvar Intraepithelial Neoplasia, Vulvar High Grade Squamous Intraepithelial Lesion, Vaccine, HPV-related Malignancy, HPV-related Carcinoma, HPV-related Cervical Carcinoma, HPV-related Anal Squamous Cell Carcinoma, HPV Positive Oropharyngeal Squamous Cell Cancer
Medical subject headings
Papillomavirus Infections, Uterine Cervical Dysplasia, Carcinoma in Situ, Vulvar Neoplasms, Vulvar Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E7 TCR cellsBiological

    Also called E7 T Cell Receptor (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.

  • AldesleukinDrug

    Also called Interleukin-2, IL-2, Proleukin

    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.

  • FludarabineDrug

    Also called Fludara

    Part of the non-myeloablative lymphocyte-depleting preparative regimen.

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    Part of the non-myeloablative lymphocyte-depleting preparative regimen.

  • EKGDiagnostic test

    Also called Electrocardiogram

    Screening/Baseline. Follow-up (end of treatment).

  • BiopsyProcedure or surgery

    Also called Bx

    Screening/Baseline. Following treatment (6 weeks post treatment preferred) and at disease progression only.

  • Chest CT and MRI or PETDiagnostic test

    Also called Chest computed tomography and magnetic resonance imaging and positron emission tomography

    Screening/Baseline. Follow-up (end of treatment). 40 days (+/- 2 weeks) after cell infusion; additional visits as indicated.

  • PFTDiagnostic test

    Also called Pulmonary function test

    Screening/Baseline.

  • GranisetronDrug

    Also called Kytril, Sancuso, Sustol

    Supportive medication for nausea/vomiting/anorexia. 0.01 mg/kg intravenous (IV) every(q) day as needed (prn).

  • OndansetronDrug

    Also called Zofran

    Supportive medication for nausea/vomiting/anorexia. Ondansetron 10mg intravenous (IV) every(q) 8 hours(hr) as needed (prn).

  • DroperidolDrug

    Also called Inapsine, Droleptan, Dridol, Xomolix

    Supportive medication for nausea/vomiting/anorexia. 1mg intravenous (IV) at 4-6 hours(h) as needed (prn).

  • ProchlorperazineDrug

    Also called Compazine

    Supportive medication for nausea/vomiting/anorexia. 25mg per rectum (PR) as needed (prn) or 10mg intravenous (IV) every(q) 6hours(h) prn.

  • Diphenoxylate HCLDrug

    Also called Diphenoxylate Hydrochloride

    Supportive medication for diarrhea. 2.5mg by mouth (po) every(q) 3 hours(h) as needed (prn).

  • Atropine sulfateDrug

    Also called Atropen

    Supportive medication for diarrhea. 25mcg by mouth (po) every(q) 3 hours(h) as needed (prn).

  • Codeine sulfateDrug

    Also called Codeine

    Supportive medication for diarrhea. 30-60mg by mouth (po) every(q) 4 hours(h) as needed (prn).

  • LoperamideDrug

    Also called Imodium A-D

    Supportive medication for diarrhea. 2mg by mouth (po) every(q) 3 hours(h) as needed (prn).

  • IndomethacinDrug

    Also called Indocin, Tivorbex

    Supportive medication for fever. 50-75mg by mouth (po) every(q) 8 hours(h).

  • AcetaminophenDrug

    Also called Tylenol

    Supportive medication for fever. 650mg by mouth (po) every 4 hours (q) 4hr.

  • Diphenhydramine HCLDrug

    Also called Diphenhydramine Hydrochloride, Benadryl, Unisom, ZzzQuil

    Supportive medication for pruritis. 25-50mg by mouth (po) every 4 hours (q) 4hr as needed (prn).

  • Hydroxyzine HCLDrug

    Also called Atarax

    Supportive medication for pruritis. 10-20mg by mouth (po) every 6 hours(h), as needed (prn).

  • MeperidineDrug

    Also called Demerol

    Supportive medication for chills. 25-50mg intravenous (IV) every 1 hour (q1hr), as needed (prn).

Study groups in NCT02858310
Study groupRoleWhat they receive
Arm 1: Phase IExperimentalNon-myeloablative, lymphocyte depleting preparative regimen, followed by E7 T cell receptor (TCR) Cells at escalating doses, followed by aldesleukin.
Receives: Biological: E7 TCR cells; Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide; Diagnostic Test: EKG; Procedure: Biopsy; Diagnostic Test: Chest CT and MRI or PET; Diagnostic Test: PFT; Drug: Granisetron; Drug: Ondansetron; Drug: Droperidol; Drug: Prochlorperazine; Drug: Diphenoxylate HCL; Drug: Atropine sulfate; Drug: Codeine sulfate; Drug: Loperamide; Drug: Indomethacin; Drug: Acetaminophen; Drug: Diphenhydramine HCL; Drug: Hydroxyzine HCL; Drug: Meperidine
Arm 2: Phase IIExperimental1 x 10^e11 E7 Cells that was determined in Phase I + aldesleukin.
Receives: Biological: E7 TCR cells; Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide; Diagnostic Test: EKG; Procedure: Biopsy; Diagnostic Test: Chest CT and MRI or PET; Diagnostic Test: PFT; Drug: Granisetron; Drug: Ondansetron; Drug: Droperidol; Drug: Prochlorperazine; Drug: Diphenoxylate HCL; Drug: Atropine sulfate; Drug: Codeine sulfate; Drug: Loperamide; Drug: Indomethacin; Drug: Acetaminophen; Drug: Diphenhydramine HCL; Drug: Hydroxyzine HCL; Drug: Meperidine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase II: Overall Response Rate Partial Response + Complete Response (PR +CR)

    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.

    Measured: At 12 weeks, every 3 months x 3, and every 6 months for approximately 5 years

  2. Phase I: Number of Dose Limiting Toxicities (DLT)

    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.

    Measured: From the day of cell infusion (Day 0) to Day +30

Secondary outcomes (1)

  1. Progression-free Survival

    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.

    Measured: From the time of cell infusion (Day 0) until documented progressive disease; a maximum of 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2016 (estimated)
  2. Study start27 Jan 2017
  3. Primary completion2 Jul 2025
  4. Study completion2 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
224 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02858310
Sponsor's protocol ID
160154
Other IDs
16-C-0154
Status last verified
Feb 2026
First submitted
4 Aug 2016
Last updated
9 Mar 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.

Publications

  • Draper LM, Kwong ML, Gros A, Stevanovic S, Tran E, Kerkar S, Raffeld M, Rosenberg SA, Hinrichs CS. Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6. Clin Cancer Res. 2015 Oct 1;21(19):4431-9. doi: 10.1158/1078-0432.CCR-14-3341.

    PubMed 26429982

  • Stevanovic S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, Restifo NP, Rosenberg SA, Hinrichs CS. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015 May 10;33(14):1543-50. doi: 10.1200/JCO.2014.58.9093. Epub 2015 Mar 30.

    PubMed 25823737

  • Hinrichs CS, Restifo NP. Reassessing target antigens for adoptive T-cell therapy. Nat Biotechnol. 2013 Nov;31(11):999-1008. doi: 10.1038/nbt.2725. Epub 2013 Oct 20.

    PubMed 24142051

  • Jin BY, Campbell TE, Draper LM, Stevanovic S, Weissbrich B, Yu Z, Restifo NP, Rosenberg SA, Trimble CL, Hinrichs CS. Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. JCI Insight. 2018 Apr 19;3(8):e99488. doi: 10.1172/jci.insight.99488. eCollection 2018 Apr 19.

    PubMed 29669936

  • 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.

    PubMed 33558725

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing E7 TCR cells, Aldesleukin and Fludarabine in people with Papillomavirus Infections and Cervical Intraepithelial Neoplasia, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Mar 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02858310, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026.

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