Rutgers and Iovance Assess E7 TCR T-Cell Therapy in Phase 1/2 Trial for HPV-Associated Tumors

Rutgers and collaborator Iovance Therapeutics are currently evaluating an E7 T-cell receptor (TCR)-T cell therapy (referred to as “E7 TCR-T cells”) for the treatment of various locoregionally advanced HPV-associated tumors in a phase 1/2 clinical trial (NCT05639972).¹ For this installment of Clinical Trials in Progress, CGTLive® is taking a closer look at this ongoing study.

The trial, which was launched on August 11, 2025, has an estimated completion date of October 1, 2026. According to the ClinicalTrials.gov page, which was most recently updated on August 19, 2025, the study is considered single-center and is actively recruiting at Rutgers Cancer Institute and RWJBarnabas Health - Robert Wood Johnson University Hospital, both of which are located in New Brunswick, New Jersey. The trial is expected to enroll 15 participants in total. Christian S. Hinrichs, MD, codirector of the Duncan and Nancy MacMillan Cancer Immunology and Metabolism Center of Excellence (CIMCoE) and the chief of the Section of Cancer Immunotherapy at RWJBarnabas Health, is serving as the trial’s principal investigator.

In the single-arm trial, patients will undergo lymphodepletion with cyclophosphamide and fludarabine before being treated with the cell therapy. In addition to the E7 TCR-T cells, which will be administered as a single intravenous dose, patients will also receive high-dose aldesleukin (720,000 IU/kg IV) as an adjuvant therapy. The aldesleukin will be given every 8 hours for up to 3 doses, with dosing to cease in the event of any related cases of grade 3 or higher toxicity, excepting flushing, fever, chills, or hemodynamic changes that respond to crystalloid infusion.

Initial follow-up will take place at 3 weeks and 6 weeks posttreatment, with imaging studies assessing tumor response at 6 weeks. After this assessment, patients will be referred to their primary oncology team for definitive therapy.

“HPV-associated malignancies include cancers of the cervix, oropharynx, anus, vulva, vagina, and penis,” Rutgers wrote in an abstract of the project details published on the National Institutes of Health (NIH) website.² “They cause thousands of deaths in the United States each year. Treatments for metastatic disease rarely provide lasting palliation and have minimal curative potential. First-line therapy increasingly includes immune checkpoint blockade in combination with chemotherapy, limiting the options for subsequent treatment. Hence, there is a compelling need for more effective treatments for advanced-stage disease.”

The trial’s primary end point is feasibility as assessed by the proportion of patients who finish treatment without experiencing an event fitting criteria for failure of feasibility, as of 6 weeks posttreatment. The trial’s secondary end points include the objective response rate at 6 weeks posttreatment, as determined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1 or PERCIST, and the disease free survival at 2 years and 5 years posttreatment, as determined by Kaplan-Meier method.

The study is open to adult patients aged 18 years and older with histologically confirmed carcinoma originating from a primary tumor site and disease stage specified in the protocol. Eligible tumors must be positive for the HPV16 genotype, as determined by testing conducted in a Clinical Laboratory Improvement Amendments (CLIA)–certified laboratory. Participants must also express the HLA-A02:01 allele, with testing likewise performed in a CLIA-certified laboratory. Enrollment may occur based on low-resolution HLA typing identifying HLA-A02; however, confirmation of the HLA-A*02:01 allele is required prior to apheresis. Patients must have measurable disease according to RECIST version 1.1 or PERCIST criteria and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.

Women under the age of 55 and all women who have had a menstrual period within the past 12 months must have a negative pregnancy test prior to enrollment; pregnancy testing is not required for women who have undergone bilateral oophorectomy or hysterectomy. Men and women of childbearing potential must agree to use effective contraception, such as intrauterine devices, hormonal or barrier methods, abstinence, tubal ligation, or vasectomy, prior to study entry and for at least four months following treatment. Participants must also be seronegative for HIV antibody, hepatitis B surface antigen, and hepatitis C antibody. If hepatitis C antibody testing is positive, confirmatory testing by reverse transcription polymerase chain reaction must demonstrate absence of detectable HCV RNA.

Adequate organ and marrow function is required at screening. This includes leukocyte counts greater than 3,000/mcL, absolute neutrophil counts above 1,500/mcL, platelet counts exceeding 100,000/mcL, and hemoglobin levels above 9.0 g/dL. Total bilirubin must be within normal institutional limits, with the exception of participants with Gilbert’s syndrome, for whom total bilirubin levels below 3.0 mg/dL are acceptable. Liver enzymes must not exceed 2.5 times the upper limit of normal, and renal function must be adequate, defined as a calculated creatinine clearance greater than 50 mL/min/1.73 m² for participants with elevated serum creatinine. Coagulation parameters must show an international normalized ratio or activated partial thromboplastin time no greater than 1.5 times the upper limit of normal, unless the participant is receiving anticoagulation therapy within a therapeutic range and has no history of severe bleeding. Participants must be able to understand and sign written informed consent and must agree to participate in protocol-defined long-term gene therapy follow-up and biospecimen collection studies. Minor surgical procedures within three weeks prior to enrollment are permitted provided all related toxicities have resolved to grade 1 or less.

Patients will be excluded if they have received prior systemic therapy or definitive chemoradiation for the cancer being treated on this protocol, or if they are currently receiving another investigational agent. Additional exclusion criteria include a history of severe allergic reactions to agents of similar chemical or biological composition, or the presence of uncontrolled intercurrent illnesses such as active infection, symptomatic congestive heart failure, unstable angina, significant cardiac arrhythmias, or psychiatric or social conditions that would limit protocol compliance. Participants with evidence of HLA-A*02:01 allele loss, damaging mutations, or other molecular resistance mechanisms identified through clinical or research sequencing are not eligible.

Cardiac exclusion criteria include a documented left ventricular ejection fraction of 45% or less, as well as clinically significant atrial or ventricular arrhythmias, including atrial fibrillation, ventricular tachycardia, or second- or third-degree heart block. Participants older than 50 years of age will also undergo cardiac evaluation. Individuals with baseline oxygen saturation below 92% on room air will be excluded, although they may be reconsidered if the underlying cause of hypoxia resolves. Because of potential risks to nursing infants, breastfeeding must be discontinued in participants treated with E7 TCR T cells, and similar risks may apply to other agents used in the study.

Patients with systemic immunodeficiency, including acquired conditions such as HIV or primary immunodeficiencies such as severe combined immunodeficiency disease, are not eligible, as the investigational therapy relies on an intact immune system. Participants receiving immunosuppressive medications, including corticosteroids, are excluded unless they meet protocol-defined exceptions. Individuals with potentially severe autoimmune diseases, including Crohn disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis, autoimmune pancreatitis, or systemic lupus erythematosus, are not eligible, although patients with less severe autoimmune conditions such as hypothyroidism or vitiligo may participate. Patients with prior or concurrent malignancies may be eligible if the natural history or treatment of those cancers is unlikely to interfere with study assessments; examples include carcinoma in situ, localized cutaneous skin cancers, low-grade non–muscle invasive bladder cancer, and low-grade prostate cancer. Receipt of a live vaccine within 30 days prior to enrollment is exclusionary. Final eligibility determination may be made at the discretion of the principal investigator if participation is deemed not to be in the patient’s best interest or could compromise safety or study integrity.

According to Rutgers, the E7 TCR-T cell therapy project has funding from the National Cancer Institute equaling $627,893.00 for 2025.² The budget start date was August 1, 2025 and the budget end date is July 31, 2026.

“We have developed a new type of treatment for HPV-associated cancers that targets the E7 oncoprotein by administering high-avidity autologous T cells directed against E7 by a gene-engineered T-cell receptor (E7 TCR-T cells),” Rutgers added in the abstract.² “E7 TCR-T cell therapy has demonstrated safety and clinical activity in treatment-refractory, metastatic HPV- associated metastatic cancers. In a phase I clinical trial, no dose-limiting toxicity was identified. Clinical activity included regression of widespread, bulky cancer and complete regression of most tumors in some patients – including immune checkpoint blockade-refractory tumors. Translational research identified immunomolecular mechanisms of resistance, which now permits for screening of patients to treat only those whose tumors demonstrate an absence of resistance markers.”

Notably, earlier this year CGTLive interviewed several experts about the challenges and opportunities of bringing cell therapy to solid tumors. Among those interviewed was Evan Weber, PhD, an assistant professor of pediatrics at Children's Hospital of Philadelphia. In his interview, he spoke about the importance of addressing T-cell exhaustion in order to make chimeric antigen receptor T-cell (CAR-T) therapy viable in solid tumors, but also shared his thoughts on the broader array of cell therapy approaches currently being explored to treat solid tumors, such as tumor-infiltrating lymphocyte (TIL) therapies and TCR T-cell therapy, and how improved CAR-T therapies may fit into that landscape. He suggested that different approaches may end up carving out different niches where they are shown to be most effective.

REFERENCES
1. E7 T-cell receptor (TCR) -T cell induction therapy for locoregionally advanced HPV-associated cancers. Website. ClinicalTrials.gov. Updated August 19, 2025. Accessed December 22, 2025. https://clinicaltrials.gov/study/NCT05639972
2. E7 TCR-T cell therapy for HPV-associated cancers. Website. NIH.gov. Accessed December 22, 2025. https://reporter.nih.gov/project-details/11125763