A Phase II Study of Neoadjuvant E7 TCR T Cell Immunotherapy for Borderline Resectable and Unresectable Stage I HPV-Associated Oropharyngeal Cancer

Summary

Background: Researchers have found a new way to treat cancer. 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 white blood 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 and this study is looking at those cause by HPV-16.

Objective: The purpose of this study is to find out if injecting E7 TCR T cells directly into cancer tumor(s) can be done without delaying standard treatment for stage I oropharyngeal cancer, which may include surgery or radiation therapy with chemotherapy.

Eligibility: People aged 18 and older with borderline resectable or unresectable Stage I, 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 which may include additional laboratory or imaging tests. A biopsy of the primary tumor may be performed before getting the cell injection and approximately 4 weeks after the cell injection.

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 white 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. The cells are grown in the lab and given back to the participant through an injection into the participant's tumor. It takes 11-15 days to grow the cells.

Once the cells are ready, participants will receive an injection of E7 TCR T cells directly into the primary tumor and any lymph nodes that can be seen or felt on physical exam. The injection will be done in the clinic or the operating room and may require general anesthesia. Participants will recover in the hospital until they are well enough to go home, which will be about 1-2 days after the cell injection.

Participants will have follow-up visits starting 2 weeks after cell injection. These will be visits to monitor the safety of the treatment and to evaluate the response of the cancer to the treatment. If the cancer appears to be growing at the 2-week visit, participants will go back to their local doctor for further care. If the cancer is not growing, participants will return for another follow-up visit 4 weeks after cell injection to see how the cancer is responding. Regardless of whether the cancer is shrinking or not, all participants will be referred to their home physician for further care after the 4-week visit.

After receiving cell therapy, participants will be followed on a long-term gene therapy protocol. 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, 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 cell injection. If participants are not able, to return to the NIH annually, they may be contacted at home and asked to have records sent from their local doctor. 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.

Conditions

• Papillomavirus Infections
• Oropharyngeal Neoplasms

Interventions

BIOLOGICAL

E7 TCR

The injection will be approximately 3x10\^8 E7 TCR T cells, unless fewer cells are generated, at each site of organ involvement (i.e. primary tumor, palpable lymph node (s)) in approximately 1-2 mL of volume.

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Christian S Hinrichs, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-07-29

Primary Completion

2020-09-17

Completion

2020-09-17

FDA Drug

Yes

Countries

• United States

Study Locations