Trial Title:
E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers
NCT ID:
NCT05639972
Condition:
HPV-Associated Cervical Carcinoma
HPV-Related Carcinoma
HPV-Related Malignancy
HPV Positive Oropharyngeal Squamous Cell Carcinoma
HPV-Related Adenocarcinoma
HPV-Related Adenosquamous Carcinoma
HPV-Related Squamous Cell Carcinoma
HPV-Related Anal Squamous Cell Carcinoma
HPV-Related Penile Squamous Cell Carcinoma
HPV-Related Vulvar Squamous Cell Carcinoma
HPV-Related Endocervical Adenocarcinoma
Cervical Cancer
Oropharynx Cancer
Anal Cancer
Vulvar Cancer
Penile Cancer
Vaginal Cancer
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Adenocarcinoma
Uterine Cervical Neoplasms
Anus Neoplasms
Vulvar Neoplasms
Squamous Cell Carcinoma of Head and Neck
Vaginal Neoplasms
Oropharyngeal Neoplasms
Penile Neoplasms
Carcinoma, Adenosquamous
Aldesleukin
Conditions: Keywords:
HPV
Cell therapy
Adoptive cell therapy
Immunotherapy
Radiation
Chemoradiation
CAR-T, cell therapy
Tumor infiltrating lymphocyte
TCR
T cell
Gene therapy
Cervical cancer
Oropharyngeal cancer
Anal cancer
Vulvar cancer
Vaginal cancer
Penile cancer
Induction therapy
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
This is a single-arm feasibility study.
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 will be
administered every 8 hours as an inpatient for up to 3 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:
The goal of this study is to determine the feasibility of administration of a single dose
of E7 TCR-T cells as induction therapy prior to definitive treatment (chemoradiation or
surgery) of locoregionally advanced HPV-associated cancers. The intent of E7 TCR-T cell
treatment is to shrink or eliminate tumors and thereby facilitate definitive therapy and
increase overall survival.
This study seeks to determine 1) if E7 TCR-T cells can be administered without undue
delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, and
3) the disease-free survival rate at 2 and 5 years.
Participants will undergo an apheresis procedure to obtain T cells that will be
genetically engineered to generate E7 TCR-T cells. They will receive a conditioning
regimen, a single infusion of their own E7 TCR-T cells, and adjuvant aldesleukin.
Participants will follow up to assess safety and determine tumor response and will return
to their primary oncology team for definitive therapy.
Detailed description:
This is a single-arm, single-cohort, single-center, feasibility study to determine the
feasibility of E7 TCR-T cell induction therapy for locoregionally advanced human
papillomavirus (HPV)-associated cancers (LAHPVC). Participants must have LAHPVC with
HPV-16-positive cancer (tumor test) and the human leukocyte antigens (HLA)-A*02:01 allele
(blood test). Participants will undergo apheresis for generation of autologous,
gene-engineered, E7 TCR-T cells. One week after apheresis, they will receive a
non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and
fludarabine. Conditioning will be followed by a single infusion of E7 TCR T cells and
adjuvant high-dose aldesleukin. Participants will follow up 3 weeks and 6 weeks after
treatment. Tumor response will be assessed by imaging studies at the 6-week time point.
Participants will be referred back to their primary oncology team for definitive therapy
after the 6-week assessment (or earlier if tumors do not appear to be responding).
Participants will be followed to determine 2- and 5-year disease free survival.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed carcinoma of a primary tumor site and stage indicated in
Table 3 of the protocol.
2. Tumor with HPV16 genotype as determined by testing performed in a Clinical
Laboratory Improvement Amendments (CLIA) certified laboratory.
3. HLA-A*02:01 allele determined by testing performed in a 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 per RECIST Criteria Version 1.1 or PERCIST.
5. Age > 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
7. 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.
8. 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.
9. Seronegative for HIV antibody, hepatitis B surface antigen (sAg), and hepatitis C
antibody. If a hepatitis C antibody test is positive, then testing for antigen by
reverse transcription polymerase chain reaction (RT-PCR) must be negative.
10. Participants must have organ and marrow function as defined below:
1. Leukocytes > 3,000/Mantle cell lymphoma (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 aminotransferase (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.
11. Participants must be able to understand and be willing to sign the written informed
consent document.
12. Participants must agree to participate in protocol CINJ 192103 (Pro2021002307) for
gene therapy long term follow up and in protocol Cancer Institute of New Jersey
(CINJ) 192002 (Pro2021000281) for biospecimen collection study.
Note: Patients 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. Prior systemic therapy or definitive chemoradiation for the cancer that is being
treated on this protocol.
2. Current treatment with another investigational agent.
3. History of severe allergic reactions to compounds of similar chemical or biological
composition to agents used in this study.
4. 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.
5. Subjects with HLA-A*02:01 damaging mutation or allele loss or other molecular
resistance detected by research or clinical sequencing will not be eligible.
6. 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
7. Participants with baseline screening pulse oxygen level of <92% on room air will not
be eligible. If the underlying cause of hypoxia improves, they may be reevaluated.
8. 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.
9. 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.
10. Participants on immunosuppressive drugs including corticosteroids unless meeting
criteria outlined in Section 6.1 (Prohibited Medications).
11. 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.
12. 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
13. Subjects who received a live vaccine within 30 days prior to enrollment are not
eligible.
14. 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
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
Contact:
Last name:
Tobi Adewale
Phone:
732-710-2406
Email:
olutobi@cinj.rutgers.edu
Start date:
October 12, 2024
Completion date:
October 1, 2026
Lead sponsor:
Agency:
Christian Hinrichs
Agency class:
Other
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/NCT05639972
