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

Cervical Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05686226
• Other study ID #: 192204
• Secondary ID: Pro2022002259
• Status: Recruiting
• Phase: Phase 2
• Start date: March 7, 2023
• Est. completion date: January 1, 2025

Study information

• Verified date: October 2023
• Source: Rutgers, The State University of New Jersey
• Contact: Carrie Snyder
• Phone: 732-235-7356
• Email: cs1449[@]cinj.rutgers.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: January 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 1.114.

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 > 8.0 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.

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Anal Cancer
• Anus Neoplasms
• Carcinoma
• Carcinoma, Adenosquamous
• Carcinoma, Squamous Cell
• Cervical Cancer
• HPV Positive Oropharyngeal Squamous Cell Carcinoma
• HPV-Related Anal Squamous Cell Carcinoma
• HPV-Related Carcinoma
• HPV-Related Cervical Carcinoma
• HPV-Related Malignancy
• HPV-Related Penile Squamous Cell Carcinoma
• HPV-Related Squamous Cell Carcinoma
• HPV-Related Vulvar Squamous Cell Carcinoma
• Metastatic Cancer
• Oropharyngeal Neoplasms
• Oropharynx Cancer
• Penile Cancer
• Penile Neoplasms
• Squamous Cell Carcinoma of Head and Neck
• Throat Cancer
• Uterine Cervical Neoplasms
• Vaginal Cancer
• Vaginal Neoplasms
• Vulva Cancer
• Vulvar Neoplasms

Intervention

Biological:
• E7 TCR-T cells
Participants will receive a conditioning regimen (cyclophosphamide and fludarabine), E7 TCR-T cells as a single infusion, and adjuvant high-dose aldesleukin.

Locations

Country	Name	City	State
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	RWJBarnabas Health - Robert Wood Johnson University Hospital	New Brunswick	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Christian Hinrichs

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Tumor response	Objective tumor response as measured by RECIST	Five years
Secondary	Adverse Events	Adverse events as measured by CTCAE	5 years