Skip to main content

T-cell Receptor Gene Therapy Targeting HPV-16 E6 in Treating Patients with Metastatic, Recurrent, or Refractory HPV-Related Cancer

Trial Status: Complete

This phase I / II trial studies the side effects and best dose of T-cell receptor gene therapy targeting human papillomavirus (HPV)-16 E6 and to see how well it works in treating patients with HPV-related cancer that has spread to other places in the body (metastatic), has come back (recurrent), or has not responded to treatment (refractory). T-cell receptor gene therapy targeting HPV-16 E6 may kill cancer cells by blocking a gene that helps HPV-related cancer form and grow. Giving chemotherapy drugs, such as cyclophosphamide and fludarabine phosphate, before gene therapy may temporarily suppress the immune system to improve the chances that the experimental cells will be able to survive in the body. Giving aldesleukin after gene therapy may help the cells stay alive longer.

Inclusion Criteria

  • Measurable metastatic or refractory/recurrent 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*02:01-positive
  • All patients must have received prior first line standard therapy or declined standard therapy, and have been either non-responders (progressive disease) or have recurred
  • Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible; lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible; patients with surgically resected brain metastases are eligible
  • Able to understand and sign the informed consent document
  • Willing to sign durable power of attorney
  • Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
  • Life expectancy of greater than 3 months
  • Patients of both genders must be willing to practice birth control from the time of enrollment on this study up to 4 months after treatment; patients must be willing to undergo testing for HPV-16 prior to becoming pregnant
  • Women of child bearing potential must have a negative pregnancy test
  • Seronegative for human immunodeficiency virus (HIV) antibody
  • 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 transcriptase (RT)-PCR and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative
  • Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim
  • White blood cell (WBC) >= 3000/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin > 8.0 g/dL
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< to 2.5 times the upper limit of normal
  • Serum creatinine =< to 1.6 mg/dL
  • Total bilirubin =< 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 4 weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen; note: patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria

Exclusion Criteria

  • Women of childbearing potential who are pregnant or breastfeeding
  • 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, obstructive or restrictive pulmonary disease
  • Any form of primary immunodeficiency (such as severe combined immunodeficiency disease)
  • Concurrent opportunistic infections
  • Concurrent systemic steroid therapy
  • History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine phosphate (fludarabine)
  • History of coronary revascularization or ischemic symptoms
  • 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 >= 60 years old


National Cancer Institute Surgery Branch
Contact: Christian Sutter Hinrichs
Phone: 301-435-3027
National Institutes of Health Clinical Center
Contact: Christian Sutter Hinrichs
Phone: 301-435-3027


I. To determine a safe dose of administration of autologous T cells transduced with an anti-HPV-16 E6 T-cell receptor (TCR) and aldesleukin to patients following a nonmyeloablative but lymphodepleting preparative regimen.

II. To determine the objective tumor response rate (complete or partial response) and duration in patients with metastatic or recurrent/refractory HPV-16+ cancers treated with this regimen.


I. To determine the toxicity of this treatment regimen.

II. To study immunologic correlates associated with E6 TCR gene therapy for HPV16+ cancers.

OUTLINE: This is a phase I, dose-escalation study of autologous anti-HPV-16 E6 T-cell receptor gene-engineered peripheral blood lymphocytes followed by a phase II study.

PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine phosphate IV piggyback (IVPB) over 30 minutes on days -5 to -1.

AUTOLOGOUS T CELLS: Patients receive autologous anti-HPV-16 E6 T-cell receptor gene-engineered peripheral blood lymphocytes IV over 20-30 minutes on day 0.

ALDESLEUKIN: Beginning within 24 hours of T-cells infusion, patients receive aldesleukin IV over 15 minutes every 8 to 24 hours for up to 5 days.

After completion of study treatment, patients are followed up at 6 weeks, every month for 3 months, every 3 months for 9 months, every 6 months for 1 year, annually for 3 years, and then periodically thereafter for 10 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
NCI - Center for Cancer Research

Principal Investigator
Christian Sutter Hinrichs

  • Primary ID 15-C-0005
  • Secondary IDs NCI-2014-02319, RD-14-VIII-09, RD-14-VII-09, 337514, P141607, 1407-1331
  • ID NCT02280811