E7 T-cell Receptor (TCR) -T Cell Induction Therapy for Locoregionally Advanced HPV-associated Cancers
Study Details
Study Description
Brief 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 cell can be administered without undue delay in definitive treatment, 2) the tumor response rate to E7 TCR-T cell treatment, 3) and 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 1/Phase 2 |
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). Treatment with T cell engineered to express the E7 TCR has demonstrated safety and clinical activity in recurrent/refractory or metastatic HPV-associated cancers, including immune checkpoint blockade-resistant tumors. 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Conditioning, E7 TCR-T cells, and aldesleukin Participants will receive a conditioning regimen consisting of cyclophosphamide 30 mg/kg daily x 2 doses and fludarabine 25 mg/m2 daily x 5 doses followed by E7 TCR-T cells up to 5e10 transduced cells IV x 1 dose, followed by aldesleukin 720,000 IU IV every 8 hours for up to 3 doses. |
Drug: Conditioning, E7 TCR-T cells, and aldesleukin
Participants will receive induction E7 TCR-T cell therapy.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Feasibility of administering E7 TCR-T cell therapy as induction treatment for LAHPVC [6 weeks]
Proportion of subjects who complete treatment without an event that meets criteria for feasibility failure
Secondary Outcome Measures
- Objective tumor response rate at 6-weeks after treatment [6 weeks]
Tumor response as assessed by imaging using Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1 or PERCIST
- 2-year and 5-year disease free survival (DFS) [5 years]
DFS will be determined using the Kaplan-Meier method
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed carcinoma of a primary tumor site and stage indicated in Table 3 of the protocol.
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Tumor with HPV16 genotype as determined by testing performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
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HLA haplotype that demonstrates the HLA-A02:01 allele as determined by testing performed in a CLIA certified laboratory. Participants may be enrolled based on low resolution typing (i.e., HLA-A02) but the HLA-A*02:01 allele type must be confirmed prior to apheresis.
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Measureable disease per RECIST Criteria Version 1.1 or PERCIST.
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Age > 18 years.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
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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.
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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.
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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.
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Participants must have organ and marrow function as defined below:
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Leukocytes > 3,000/Mantle cell lymphoma (mcL)
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Absolute neutrophil count > 1,500/mcL
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Platelets > 100,000/mcL
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Hemoglobin > 9.0 g/dL
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Total bilirubin within normal institutional limits except in participants with Gilbert's Syndrome who must have a total bilirubin < 3.0 mg/dL.
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Serum aspartate aminotransferase (AST) (SGOT)/ alanine transaminase (ALT)(SGPT) < 2.5 x upper limit of normal (ULN)
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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).
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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.
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Participants must be able to understand and be willing to sign the written informed consent document.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
Sponsors and Collaborators
- Christian Hinrichs
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Christian S Hinrichs, MD, Rutgers Cancer Institute of New Jersey
Study Documents (Full-Text)
None provided.More Information
Publications
- 192104
- Pro2022000437
- 3P30CA072720-22S1