TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers.
Nisha B Nagarsheth, Scott M Norberg, Andrew L Sinkoe...
https://pubmed.ncbi.nlm.nih.gov/33558725Actively Recruiting
Phase 2
Age: 18Years +
All Genders
ID05686226
A Phase II Trial of T Cell Receptor Gene Therapy Targeting Human Papillomavirus 16 E7 for HPV-Associated Cancers
Led by Christian Hinrichs · Updated on 2026-02-27
20
Participants Needed
3
Research Sites
N/A
Total Duration
On this page
Sponsors
C
Christian Hinrichs
Lead Sponsor
N
National Cancer Institute (NCI)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the clinical activity of immunotherapy using E7 TCR-T cells for metastatic human papillomavirus (HPV)-associated cancers, including cervical, throat, penile, vulvar, vaginal, anal, and other related cancers. This phase II trial aims to determine the tumor response rate and duration of response to this treatment, which targets the HPV16 E7 oncoprotein present in these cancers. Safety data will also be gathered as part of the study. Participants will receive a conditioning regimen composed of cyclophosphamide and fludarabine before being given a single intravenous infusion of E7 TCR-T cells. Within 24 hours of this infusion, patients will receive aldesleukin intravenously every eight hours for up to six doses, unless side effects require stopping the treatment. The treatment targets patients who have the HLA-A*02:01 allele, essential for the therapy's effectiveness. Throughout the study, participants will be monitored for tumor response over five years, along with any adverse events. Eligibility assessments include confirming measurable disease and prior treatment history. Participants will also undergo various laboratory tests and evaluations to ensure they meet safety and health criteria. The total study duration includes long-term follow-up to collect detailed information about the treatment's effects and safety.
CONDITIONS
Brief Title
E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed metastatic or refractory/recurrent HPV-16 positive cancer
- Tumor with HPV16 genotype confirmed by certified laboratory testing
- Presence of HLA-A*02:01 allele confirmed by certified laboratory testing
- Measurable disease as assessed by RECIST Criteria Version 1.1
- Age 18 years or older
- ECOG performance status of 0 or 1 at screening
- Prior receipt of first line standard therapy or declined standard therapy
- Formal decline of first and second-line standard treatment options
- Patients with up to three brain metastases treated and clinically stable
- Negative pregnancy test for eligible women and agreement to use contraception
- Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody
- Adequate organ and marrow function as defined by specified laboratory values
- More than four weeks since prior systemic therapy with recovery from adverse events
- Ability to understand and sign informed consent
- Agreement to participate in long term follow up and biospecimen collection protocols
You will not qualify if you...
- Uncontrolled illnesses such as active infection, heart failure, unstable angina, arrhythmia, or psychiatric/social issues
- History of severe allergic reactions to similar compounds
- History of coronary revascularization or ischemic symptoms without normal cardiac stress test
- Documented left ventricular ejection fraction (LVEF) ≤ 45% or significant arrhythmias
- Baseline oxygen saturation below 92% on room air
- Presence of HLA-A*02:01 damaging mutation or allele loss
- Breastfeeding during treatment with E7 TCR T cells
- Systemic immunodeficiency including HIV or primary immunodeficiencies
- Use of immunosuppressive drugs including corticosteroids unless allowed
- Severe autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, or systemic lupus erythematosus
- Prior or concurrent malignancies interfering with safety or efficacy assessments
- Receipt of live vaccine within 30 days prior to enrollment
- Investigator determination that participation is not in the subject's best interest or may jeopardize safety or data integrity
AI-Screening
AI-Powered Screening
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2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 3 days for conditioning and infusion, plus up to 2 days for aldesleukin dosing
Participants receive a conditioning regimen with cyclophosphamide and fludarabine, followed by a single infusion of E7 TCR-T cells. Within 24 hours after infusion, participants receive aldesleukin intravenously every eight hours for up to six doses, with dosing adjustments based on toxicity and investigator discretion.
Continuous inpatient visits during treatment
Follow-up
Duration - Up to 5 years
Participants are monitored for tumor response, adverse events, and long-term outcomes after treatment completion.
Regular follow-up visits as scheduled by the study team
Trial Site Locations
Total: 3 locations
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
2
Rutgers Cancer Institute
New Brunswick, New Jersey, United States, 08901
Actively Recruiting
3
RWJBarnabas Health - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08901
Actively Recruiting
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Research Team
T
Tobi Adewale
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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