A Feasibility Study of E7 TCR-T Cell Induction Therapy for Locoregionally Advanced HPV-Associated Cancers
Primary Objective:
- To determine the feasibility of administering E7 TCR-T cell therapy as induction treatment for LAHPVC
Secondary Objectives:
- To determine the objective tumor response rate at 6-weeks after treatment
- To assess 2-year and 5-year disease free survival (DFS)
- To collect biospecimens for exploratory translational research
Stomach
Cervix
Other Male Genital
Lip, Oral Cavity and Pharynx
Other Female Genital
- Rutgers Cancer Institute of New Jersey
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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.