E7 TCR-T Cells with Aldesleukin for the Treatment of Recurrent/Refractory or Metastatic HPV-16 Positive Cancers

Inclusion Criteria

• Histologically or cytologically confirmed metastatic or refractory/recurrent HPV-16+ cancer
• Tumor with HPV16 genotype as determined by testing performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory
• Human leukocyte antigen (HLA)-A*02:01 allele as 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
• Measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at screening
• Must have received prior first line standard therapy or have declined standard therapy
• Standard treatment options for first and second-line therapy must be presented and formally declined
• 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
• Negative pregnancy test for women under 55 and all women who have had a menstrual period in the last 12 months. A pregnancy test is not required for women who have had a bilateral oophorectomy or hysterectomy
• 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
• Seronegative for human immunodeficiency virus (HIV) antibody, hepatitis B antigen, and hepatitis C antibody. If a hepatitis C antibody test is positive, then testing for antigen by reverse transcriptase-polymerase chain reaction (RT-PCR) for hepatitis C virus (HCV) ribonucleic acid (RNA) must be negative
• Leukocytes > 3,000/mcL
• Absolute neutrophil count > 1,500/mcL
• Platelets > 100,000/mcL
• Hemoglobin > 8.0 g/dL
• Total bilirubin within normal institutional limits except in participants with Gilbert’s syndrome who must have a total bilirubin < 3.0 mg/dL
• Serum aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x upper limit of normal (ULN)
• Calculated creatinine clearance (CrCl) > 50 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal (by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation)
• 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 prothrombin time (PT) or aPTT within therapeutic range and no history of severe hemorrhage
• More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the E7 TCR cells
• Participants must be able to understand and be willing to sign the written informed consent document
• Participants must agree to participate in protocol CINJ 192103 (Pro2021002307) for gene therapy long term follow up and in protocol 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

• 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
• History of severe allergic reactions to compounds of similar chemical or biological composition to agents used in this study
• History of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test
• Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested. The following participants will undergo cardiac evaluations: * Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or * Age >= 50 years old
• Participants with baseline screening pulse oxygen level of < 95% on room air will not be eligible. If the underlying cause of hypoxia improves, then they may be reevaluated
• 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
• 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
• 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
• Participants on immunosuppressive drugs including corticosteroids unless meeting criteria
• 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
• Participants with a second malignancy requiring treatment within the last 2 years are not eligible with the following exceptions: * Carcinoma in situ * Cutaneous skin cancers requiring only local excision
• 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