E7 TCR T Cells for Human Papillomavirus-Associated Cancers

Trial end date:
Target enrollment:
Participant gender:
Background: Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have a 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 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.
Phase 1/Phase 2
Accepts Healthy Volunteers?
Lead Sponsor:
National Cancer Institute (NCI)

1. Measurable metastatic or refractory/recurrent HPV-16+ cancer (determined by in
situ hybridization (ISH) or a polymerase chain reaction (PCR)-based test).

2. Patients must be 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 ECOG 0 or 1.

8. Patients of both genders must be willing to practice birth control from the time
of enrollment on this study up to four months after treatment. Patients must be
willing to undergo testing for HPV-16 prior to becoming pregnant after this

9. Women of childbearing potential must have a negative pregnancy test because of
the potentially dangerous effects of the treatment on the fetus. Women of
childbearing potential are defined as all women except women who are
postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as
women 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 infants
secondary to treatment of the mother with E7 TCR transduced PBL, breastfeeding
should be discontinued if the mother is treated with E7 TCR transduced PBL. These
potential risks may also apply to other agents used in this study.

10. Serology:

- 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 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 RT-PCR and be HCV RNA negative.

a. Hematology:

- Absolute neutrophil count greater than 1000/mm^3 without the support of


- 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 ALT/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.


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

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

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;


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

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 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