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
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
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.
- Brief Title: E7 TCR Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer
- Official Title: A Phase II Study of E7 TCR T Cell Induction Immunotherapy for Stage II and Stage III HPV-Associated Oropharyngeal Cancer
Clinical Trial IDs
- ORG STUDY ID:
- SECONDARY ID:
- NCT ID:
- Papillomavirus Infections
- Oropharyngeal Neoplasms
|E7 TCR||Arm 1|
The therapy called E7 TCR gives white blood cells new genes to attack cancer. This treatment
might help people with human papilloma virus (HPV)-associated oropharyngeal cancer.
To see if people with oropharyngeal cancer can be treated with E7 T cells before getting
People ages 18-65 with Stage II or III HPV-16 associated oropharyngeal cancer
Participants will be screened with:
Blood and heart tests
Tumor tissue: If this is not available, they will have a biopsy.
Participants will have a catheter inserted into a vein in the chest.
Participants will have leukapheresis. Blood will be removed through a needle in one arm, move
through a machine that takes out the white blood cells, then returned through a needle in the
other arm. The white blood cells will be modified in the lab.
Participants will be admitted to the hospital a week before treatment. They will get
chemotherapy and then the E7 TCR cells through the catheter. They will recover in the
hospital for 7-12 days. They will get a drug through the catheter for 5 days. They may get an
injection every day.
Participants will have visits every 2 weeks. This will continue until their disease goes away
or the treatment stops working. Then they will have blood tests at months 3, 6, and 12 in the
first year. Then they will have annual physical exams for 5 years. Then they will complete
annual questionnaires for 10 years.
- 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
- 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.
-To determine the feasibility of systemic treatment with E7 TCR T cells for stage II or stage
III HPV+ oropharyngeal cancer.
- Patients greater than or equal to 18 years old and less than or equal to 66 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.
- 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
|Arm 1||Experimental||1.5x1010 to 3x1010 E7 TCR T cells (based on the number of cells that can be generated in the shortened manufacturing process) will be administered intravenously over 20 to 30 minutes on day 0.|
- 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
- Measurable disease by RECIST 1.1 criteria.
- Patient age from 18 to 65 years. 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. Patients over age 66 are excluded because of a trend toward
increased incidence of severe urogenital toxicity and pulmonary toxicity with
aldesleukin in older patients.
- 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
- 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
- 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
(15-C-0141), 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 1,000/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 < 3 times ULN
- creatinine clearance- Calculated creatinine clearance (CrCl) >50mL/min/1.73m2 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
- 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.,
- Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
- 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
- Patients with a second active invasive cancer are not eligible if it may confound
assessment of response to the current therapy.
|Maximum Eligible Age:||65 Years|
|Minimum Eligible Age:||18 Years|
Primary Outcome Measures
|Measure:||The fraction who achieve a success among those who receive E7 TCR T cell administration and who can be evaluated for the two feasibility criteria, with 95% confidence intervals on the fraction reported as well.|
|Time Frame:||3 months|
|Description:||The fraction who achieve a success will be determined and reported.|
|Overall Status:||Not yet recruiting|
|Lead Sponsor:||National Cancer Institute (NCI)|
- T Cell Receptor