E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers
NCT ID: NCT05686226
Last Updated: 2025-03-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
20 participants
INTERVENTIONAL
2023-03-07
2027-01-01
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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E7 TCR-T cells
Subjects will receive a conditioning regimen, E7 TCR-T cells, and aldesleukin.
E7 TCR-T cells
Participants will receive a conditioning regimen consisting of cyclophosphamide and fludarabine. E7 TCR-T cells will be administered as a single intravenous infusion.
Aldesleukin
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.
Interventions
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E7 TCR-T cells
Participants will receive a conditioning regimen consisting of cyclophosphamide and fludarabine. E7 TCR-T cells will be administered as a single intravenous infusion.
Aldesleukin
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.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
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
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.
18 Years
ALL
No
Sponsors
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Christian Hinrichs
OTHER
National Cancer Institute (NCI)
NIH
Iovance Biotherapeutics, Inc.
INDUSTRY
Responsible Party
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Christian Hinrichs
Chief, Section of Cancer Immunotherapy
Principal Investigators
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Christian S Hinrichs, MD
Role: PRINCIPAL_INVESTIGATOR
Rutgers Cancer Institute of New Jersey
Locations
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Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
RWJBarnabas Health - Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Countries
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Central Contacts
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Facility Contacts
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References
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Nagarsheth NB, Norberg SM, Sinkoe AL, Adhikary S, Meyer TJ, Lack JB, Warner AC, Schweitzer C, Doran SL, Korrapati S, Stevanovic S, Trimble CL, Kanakry JA, Bagheri MH, Ferraro E, Astrow SH, Bot A, Faquin WC, Stroncek D, Gkitsas N, Highfill S, Hinrichs CS. TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers. Nat Med. 2021 Mar;27(3):419-425. doi: 10.1038/s41591-020-01225-1. Epub 2021 Feb 8.
Other Identifiers
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NCI-2023-02813
Identifier Type: REGISTRY
Identifier Source: secondary_id
Pro2022002259
Identifier Type: OTHER
Identifier Source: secondary_id
192204
Identifier Type: -
Identifier Source: org_study_id
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