RECRUITING

E7 TCR-T Cell Immunotherapy for Human Papillomavirus (HPV) Associated Cancers

Conditions

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 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 oropharyngeal cancer vulvar cancer tumor infiltrating lymphocytes (TIL)TIL therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase II Trial of T Cell Receptor Gene Therapy Targeting Human Papillomavirus ( HPV) 16 E7 for HPV-Associated Cancers

Quick Facts

Study Start:2023-03-07

Study Completion:2025-01-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05686226

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	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.

Inclusion Criteria

Exclusion 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.

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.

Contacts and Locations

Study Contact

Tobi Adewale

CONTACT

732-710-2406

olutobi@cinj.rutgers.edu

Principal Investigator

Christian S Hinrichs, MD

PRINCIPAL_INVESTIGATOR

Rutgers Cancer Institute of New Jersey

Study Locations (Sites)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901

United States

RWJBarnabas Health - Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08901

United States

Collaborators and Investigators

Sponsor: Christian Hinrichs

Christian S Hinrichs, MD, PRINCIPAL_INVESTIGATOR, Rutgers Cancer Institute of New Jersey

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-07

Study Completion Date2025-01-01

Study Record Updates

Study Start Date2023-03-07

Study Completion Date2025-01-01

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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