E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer
E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer
Background:

 The therapy used in this study is called E7 TCR T cell therapy. This therapy is a type of
 treatment in which a participant s T cells (a type of immune system cell) are changed in the
 laboratory to attack cancer cells. This treatment might help people with human papilloma
 virus (HPV)-associated oropharyngeal cancer. Oropharyngeal cancer is a type of head and neck
 cancer that happens in the oropharynx (the part of the throat at the back of the mouth,
 including the soft palate, the base of the tongue, and the tonsils). Certain types of the HPV
 virus can cause this kind of cancer. This study is looking at treatments for cancer caused by
 HPV-16.

 Objective:

 The purpose of this study is to determine if E7 TCR T cells can be given safely without
 delaying standard treatment for HPV-16 associated oropharyngeal cancer. Standard treatment
 may be surgery or radiation therapy with chemotherapy.

 Eligibility: People ages 18 and older with Stage II or III HPV-16 associated oropharyngeal
 cancer

 Design:

 Participants will be screened with HLA typing (a blood test needed for eligibility) and HPV
 testing of the cancer tumor (to determine if the cancer is HPV-16 positive). A new biopsy may
 be needed if tumor from an outside location is not available for HPV testing. Eligible
 participants will come to the NIH campus to have a screening evaluation which will include
 physical exam, review of medical history and current medications, blood and heart tests,
 imaging (X-ray, CT scan, MRI or PET scan), and evaluation of participant s veins that are
 used for drawing blood.

 If the participant is eligible for the study based on the screening evaluation, they will
 have a baseline evaluation prior to receiving the experimental treatment. The baseline
 evaluation may include additional laboratory or imaging tests.

 Participants will have a large IV catheter inserted into a vein to undergo a procedure called
 leukapheresis. Leukapheresis is the removal of the blood by a machine to collect specific
 blood cells. The remaining blood is returned to the body. This procedure is needed to collect
 the cells that will be modified to target the cancer. These cells will be grown in the lab
 and given back to the participant through an IV. It takes 11-15 days to grow the cells.

 While the cells are growing, the participant will be admitted to the hospital about one week
 before cell infusion. They will receive 2 types of chemotherapy through an IV catheter over 5
 days. The main purpose of the chemotherapy is to make the cells more effective in fighting
 the cancer tumors. The cells will be given through an IV catheter 1-3 days after the last
 dose of chemotherapy. Within 24 hours after the cell infusion, participants will be given a
 cell growth factor called aldesleukin through an IV. Aldesleukin is thought to help the cells
 live longer in the participant s body. Participants will recover in the hospital until they
 are well enough to go home. This is usually about 7-12 days after the cell infusion or last
 dose of aldesleukin.

 Participants will have follow-up visits starting every 2 weeks after the date of cell
 infusion. These will be visits to monitor the safety of the treatment and to evaluate the
 response of the cancer to the treatment. These visits will continue if the cancer is
 shrinking. The participant will go back to their local cancer doctor for further care if the
 cancer stops shrinking, goes away completely or gets bigger.

 Participants will have blood drawn periodically to test if the cells have grown or changed.
 These blood tests will take place immediately before the cells are given, and then at 3, 6,
 12 months for the first year and then annually. These tests can be drawn locally and sent to
 the NIH. Participants will be asked to return to the NIH annually for a physical examination
 for 5 years after they receive the cells. After that time, participants will be asked to
 fill-out a questionnaire for the next ten years, for a total follow-up period of 15 years.

 ...
Background:

 -  Human papillomavirus (HPV)+ oropharyngeal cancer is an increasingly common type of
 cancer that frequently affects young patients.

 -  The treatment for locoregionally advanced cancer carries substantial life-long
 morbidity.

 -  Although the overall prognosis for HPV+ oropharyngeal cancer is favorable, about 20
 percent of patients with stage II disease and 35 percent of patients with stage III
 disease will die within five years.

 -  Induction therapy is an area of active study in this type of cancer. The aims of
 induction therapy are to reduce the risk of disease recurrence and potentially to permit
 the study of de-intensified definitive treatment of locoregional disease.

 -  E7 TCR T cells, administered as a single infusion, have demonstrated safety and clinical
 activity in treatment-refractory metastatic HPV+ cancers.

 Objectives:

 -To determine the feasibility of systemic treatment with E7 TCR T cells for stage II or stage
 III HPV+ oropharyngeal cancer.

 Eligibility:

 -  Patients greater than or equal to 18 years old with stage II or stage III HPV+
 oropharyngeal cancer.

 -  The cancer must be HPV16+ and patient must be HLA-A 02:01+ HLA type.

 -  Patients must be treatment-naive.

 Design:

 -  This is a phase II, single arm, feasibility study of induction E7 TCR T cell therapy.

 -  Patients will receive a conditioning regimen of cyclophosphamide and fludarabine, a
 single infusion of E7 TCR T cells, and systemic aldesleukin.

 -  Patients will be referred for standard of care definitive therapy (chemoradiation or
 surgery) at the time of maximum tumor response
-  INCLUSION CRITERIA:

 -  Histologically or cytologically confirmed stage II or stage III (AJCC 8th edition)
 oropharyngeal squamous cell carcinoma that has not been treated.

 -  HPV16+ tumor and HLA-A 02:01+ HLA type (HLA-A 02 is also acceptable for determination
 of eligibility).

 -  Measurable disease by RECIST 1.1 criteria.

 -  Patient age 18 and older. Because no dosing or adverse event data are currently
 available on the use of E7 TCR T Cells in patients <18 years of age, children are
 excluded from this study. This reflects the age range of patients with the disease
 being studied.

 -  ECOG performance status 0 or 1.

 -  Women of child-bearing potential must have a negative pregnancy test because E7 TCR T
 Cells have unknown potential for teratogenic or abortifacient effects. Women of
 child-bearing potential are defined as all women who are not post-menopausal or who
 have not had a hysterectomy. Postmenopausal will be defined as women over the age of
 55 who have not had a menstrual period in at least 1 year.

 -  The effects of E7 TCR T Cells on the developing human fetus are unknown. For this
 reason and because the chemotherapy agents used in this trial are known to be
 teratogenic, women of child-bearing potential and men must agree to use adequate
 contraception (intrauterine device, hormonal or 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
 or her partner is participating in this study, she should inform her treating
 physician immediately.

 -  Seronegative for 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 be less responsive to the experimental
 treatment.

 -  Seronegative for hepatitis B antigen and hepatitis C antibody. If hepatitis C antibody
 test is positive, then the patient must be tested for the presence of antigen by
 RT-PCR and be HCV RNA negative.

 -  Must be willing to participate in Gene Therapy Long Term Followup Protocol, which will
 follow patients for up to 15 years per Food and Drug Administration (FDA)
 requirements.

 -  Patients must have organ and marrow function as defined below:

 -  leukocytes- greater than or equal to 3,000/mcL

 -  absolute neutrophil count- greater than or equal to 1,500/mcL

 -  platelets- greater than or equal to 100,000/mcL

 -  hemoglobin- greater than or equal to 9.0 g/dL

 -  total bilirubin- within normal institutional limits except in patients with
 Gilbert s Syndrome who must have a total bilirubin < 3.0 mg/dL

 -  AST(SGOT)/ALT(SGPT)- Serum ALT/AST < 2.5 times ULN

 -  creatinine clearance- Calculated creatinine clearance (CrCl) >50mL/min/1.73m(2)
 for patients with creatinine levels above institutional normal (by the Chronic
 Kidney Disease Epidemiology Collaboration (CKD-EPI) equation)

 -  Ability of subject to understand and the willingness to sign a written informed
 consent document.

 EXCLUSION CRITERIA:

 -  Patients who are receiving any other investigational agents.

 -  History of severe allergic reactions attributed to compounds of similar chemical or
 biologic composition to agents used in study.

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or 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.

 -  There is an unknown but potential risk for adverse events in nursing infants secondary
 to treatment of the mother with E7 TCR T Cells. For this reason, women may not
 breastfeed while receiving study treatment and for one year after the study treatment
 ends. These potential risks may also apply to other agents used in this study.

 -  Patients with any form of 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. Patients who have decreased immune competence may
 be less responsive to the treatment.

 -  Current use of immunosuppressive medication, EXCEPT for the following:

 -  Intranasal, inhaled, topical steroids, or local steroid injection (e.g.,
 intra-articular injection);

 -  Systemic corticosteroids at physiologic doses less than equal to 10 mg/day of
 prednisone or equivalent;

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

 -  Patients with autoimmune diseases such as Crohn s disease, ulcerative colitis,
 rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus
 erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not
 exclusionary.

 -  Patients with a second active invasive cancer are not eligible if it may confound
 assessment of response to the current therapy.

 -  Patients who do not have a local physician to provide standard therapy post treatment.