Trial Title:
E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers
NCT ID:
NCT05686226
Condition:
Cervical Cancer
Throat Cancer
Oropharynx Cancer
Anal Cancer
Vulva Cancer
Vaginal Cancer
Penile Cancer
Metastatic Cancer
HPV-Related Malignancy
HPV-Related Carcinoma
HPV-Related Cervical Carcinoma
HPV-Related Squamous Cell Carcinoma
HPV-Related Adenocarcinoma
HPV Positive Oropharyngeal Squamous Cell Carcinoma
HPV-Associated Vaginal Adenocarcinoma
HPV-Related Adenosquamous Carcinoma
HPV-Related Endocervical Adenocarcinoma
HPV-Related Anal Squamous Cell Carcinoma
HPV-Related Penile Squamous Cell Carcinoma
HPV-Related Vulvar Squamous Cell Carcinoma
HPV Positive Rectal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Uterine Cervical Neoplasms
Anus Neoplasms
Squamous Cell Carcinoma of Head and Neck
Vaginal Neoplasms
Oropharyngeal Neoplasms
Penile Neoplasms
Carcinoma, Adenosquamous
Vulvar Neoplasms
Aldesleukin
Conditions: Keywords:
Chimeric antigen receptors (CAR-T)
Tumor infiltrating lymphocyte
TCR-T
immunotherapy
T cell
adoptive cell therapy
cellular therapy
gene therapy
human papillomavirus
HPV
E7
T cell receptor
TCR
E7 TCR
lymphocyte
cell therapy
cervical cancer
oropharyngeal cancer
anal cancer
vulvar cancer
vaginal cancer
penile cancer
tumor infiltrating lymphocytes (TIL)
TIL therapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a single-arm phase II clinical trial.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
E7 TCR-T cells
Description:
Participants will receive a conditioning regimen consisting of cyclophosphamide and
fludarabine. E7 TCR-T cells will be administered as a single intravenous infusion.
Arm group label:
E7 TCR-T cells
Other name:
E7 TCR
Other name:
HPV TCR
Other name:
TIL
Other name:
Adoptive cell transfer
Other name:
CAR-T
Other name:
TCR
Intervention type:
Drug
Intervention name:
Aldesleukin
Description:
Within 24 hours after E7 TCR-T cell infusion, aldesleukin 720,000 IU/kg IV every eight
hours will be administered for up to six doses. Aldesleukin dosing will be stopped for
aldesleukin-related grade 3 or greater toxicity other than flushing, fever, chills, or
hemodynamic changes (tachycardia or hypotension) that respond to crystalloid infusion.
Aldesleukin may also be stopped at any time at investigator discretion.
Arm group label:
E7 TCR-T cells
Other name:
Proleukin
Summary:
This is a phase II clinical trial to assess the clinical activity of immunotherapy with
E7 TCR-T cells for metastatic HPV-associated cancers. HPV-associated cancers in include
cervical, throat, penile, vulvar, vaginal, anal, and other cancers. Participants will
receive a conditioning regimen, E7 TCR-T cells, and aldesleukin. Clinical response to
treatment will be determined.
Detailed description:
This study will determine the tumor response rate for the treatment of HPV-associated
cancers with E7 TCR-T cells. E7 TCR-T cells are autologous gene-engineered T cells that
target HPV16 E7 through a T cell receptor (TCR). E7 is an HPV oncoprotein that is present
in HPV-associated cancers. Participants must have the HLA-A*02:01 allele, which is
required for tumor targeting by the E7 TCR. Treatment consists of a conditioning regimen
(cyclophosphamide and fludarabine), a single infusion of E7 TCR-T cells, and adjuvant
aldesleukin. Tumor response rate and response duration will be determined. Safety data
will also be collected.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically or cytologically confirmed metastatic or refractory/recurrent HPV-16+
cancer.
2. Tumor with HPV16 genotype as determined by testing performed in a CLIA certified
laboratory.
3. HLA-A*02:01 allele as determined by testing performed in a Clinical Laboratory
Improvement Amendments (CLIA) certified laboratory. Participants may be enrolled
based on low resolution typing (i.e., HLA-A*02) but the HLA-A*02:01 allele type must
be confirmed prior to apheresis.
4. Measurable disease as assessed by RECIST Criteria Version 1.1.
5. Age ≥ 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at screening.
7. Must have received prior first line standard therapy or have declined standard
therapy.
8. Standard treatment options for first and second-line therapy must be presented and
formally declined (Appendix VII).
9. 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 must be fully recovered from surgery.
10. Negative pregnancy test for women under 55 and all women who have had a menstrual
period in the last 12 months. A pregnancy tests is not required for women who have
had a bilateral oophorectomy or hysterectomy.
11. Men and women of child-bearing potential must agree to use adequate contraception
(i.e., intrauterine device, hormonal barrier method of birth control; abstinence;
tubal ligation or vasectomy) prior to study entry and for four months after
treatment. Should a women become pregnant or suspect she is pregnant while she is
participating in this study, she should inform her treating physician immediately.
12. Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody. If a
hepatitis C antibody test is positive, then testing for antigen by RT-PCR for
Hepatitis C (HCV) RNA must be negative.
13. Participants must have organ and marrow function as defined below:
1. Leukocytes > 3,000/microliter (mcL)
2. Absolute neutrophil count > 1,500/mcL
3. Platelets > 100,000/mcL
4. Hemoglobin > 9.0 g/dL
5. Total bilirubin within normal institutional limits except in participants with
Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL.
6. Serum aspartate transferase (AST) (SGOT)/alanine transaminase (ALT) (SGPT) <
2.5 x upper limit of normal (ULN)
7. Calculated creatinine clearance (CrCl) >50 mL/min/1.73 m2for participants with
creatinine levels above institutional normal (by the Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) equation).
8. international normalized ratio (INR) or activated partial thromboplastin time (
aPTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.
Subjects on anticoagulant therapy must have a PT or aPTT within therapeutic
range and no history of severe hemorrhage.
14. More than four weeks must have elapsed since any prior systemic therapy at the time
the patient receives the E7 TCR cells.. Adverse events from prior therapy must have
resolved to ≤grade 1 according to CTCAE Version 5.0 or have demonstrated clinical
stability for the protocol.
15. Participants must be able to understand and be willing to sign the written informed
consent document.
16. Participants must agree to participate in protocol Cancer Institute of New Jersey
(CINJ) 192103 (Pro2021002307) for gene therapy long term follow up and in protocol
CINJ 192002 (Pro2021000281) for biospecimen collection study.
Note: Participants may have undergone minor surgical procedures with the past three
weeks, as long as all toxicities have recovered to Grade 1 or less.
Exclusion Criteria: Subjects who meet any of the following criteria will be excluded from
participation in this study:
1. Uncontrolled intercurrent illness such as 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.
2. History of severe allergic reactions to compounds of similar chemical or biological
composition to agents used in this study.
3. History of coronary revascularization or ischemic symptoms unless patient has a
normal cardiac stress test.
4. Documented LVEF of less than or equal to 45% tested. The following participants 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 > 50 years old
5. Participants with baseline screening pulse oxygen level of < 92% on room air will
not be eligible. If the underlying cause of hypoxia improves, then they may be
reevaluated.
6. Subjects with HLA-A*02:01 damaging mutation or allele loss or other molecular
resistance detected by clinical or research genomic profiling will not be eligible.
7. Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with E7 TCR T cells, breastfeeding should be
discontinued if the mother is treated with E7 TCR T cells. These potential risks may
also apply to other agents used in this study.
8. Participants with a 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. Participants who have decreased immune competence may be
less responsive to the treatment.
9. Participants on immunosuppressive drugs including corticosteroids unless meeting
criteria outlined in Section 6.1 (Prohibited Medications).
10. Participants with potentially severe autoimmune diseases such as Crohn's disease,
ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune
pancreatitis, or systemic lupus erythematosus are not eligible. Patients with less
severe autoimmune diseases such as hypothyroidism, vitiligo, and other minor
autoimmune disorders are eligible.
11. Participants with prior or concurrent malignancy whose natural history or treatment
is unlikely to interfere with the safety or efficacy assessments of the
investigational regimen are eligible for this trial. Examples include, but are not
limited to:
1. Carcinoma in situ
2. Cutaneous skin cancers requiring only local excision
3. Low grade non-muscle invasive bladder cancer
4. Low grade prostate cancer Participants with prior or concurrent malignancy that
do not meet the above criteria are excluded.
12. Subjects who received a live vaccine within 30 days prior to enrollment are not
eligible.
13. Determination by the Principal Investigator that participation is not in the best
interest of the research subject or may jeopardize the safety of the subject or
integrity of the clinical trial data.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Rutgers Cancer Institute of New Jersey
Address:
City:
New Brunswick
Zip:
08901
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tobi Adewale
Phone:
732-710-2406
Email:
olutobi@cinj.rutgers.edu
Facility:
Name:
RWJBarnabas Health - Robert Wood Johnson University Hospital
Address:
City:
New Brunswick
Zip:
08901
Country:
United States
Status:
Recruiting
Contact:
Last name:
Tobi Adewale
Phone:
732-710-2406
Email:
olutobi@cinj.rutgers.edu
Start date:
March 7, 2023
Completion date:
January 1, 2025
Lead sponsor:
Agency:
Christian Hinrichs
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Rutgers, The State University of New Jersey
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05686226
