E7 TCR T Cell Therapy for HPV-Related Cancers

Recruiting at 1 trial location

Overseen By Laura A Parsons-Wandell, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Active infections, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 12 days

219 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for cancers related to HPV, a common virus, using specially modified white blood cells called E7 TCR cells, a type of T cell therapy. These lab-designed cells target and fight cancer cells with a specific HPV protein. The trial aims to find a safe dose and evaluate the treatment's effectiveness against cancers like cervical and throat cancer. Suitable participants include adults with HPV-16-associated cancer that has not responded to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it mentions that more than four weeks must have passed since any prior systemic therapy before receiving the E7 TCR cells. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that E7 TCR cells are generally safe for humans. These specially modified cells have treated tough cancers linked to HPV-16. In earlier trials, patients tolerated E7 TCR cells well, with manageable side effects. Reports from these studies indicate that the treatment has been safe for people with advanced HPV-related cancers.

While some side effects might occur, the treatment has been safe and has shown positive results in patients. The trials aim to find the right dose that balances safety and effectiveness. Ongoing research is promising, suggesting that E7 TCR cells could be a helpful option for those fighting HPV-related cancers. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for HPV-related cancers?

Researchers are excited about E7 TCR T Cell Therapy for HPV-related cancers because it uses a novel approach that harnesses the power of the immune system. Unlike traditional treatments like surgery, radiation, or chemotherapy, which directly target cancer cells, E7 TCR T Cell Therapy involves engineering the patient’s own T cells to recognize and attack cancer cells that express the HPV E7 protein. This targeted method not only has the potential to be more effective but also to reduce collateral damage to healthy cells, potentially leading to fewer side effects. Additionally, the therapy is designed to escalate in dosage in a controlled manner, which helps in optimizing its safety and efficacy.

What evidence suggests that E7 TCR cells might be an effective treatment for HPV-related cancers?

Research has shown that E7 TCR cells can locate and attack cancer cells in HPV-related cancers. These specially designed cells identify and destroy tumor cells containing the HPV-16 E7 protein. Early results suggest that this method has helped shrink tumors in some patients with HPV-related cancers. In this trial, participants in Arm 1 will receive E7 TCR cells at escalating doses, followed by aldesleukin. Arm 2 will involve a fixed dose of E7 TCR cells determined in Phase I, also followed by aldesleukin. E7 TCR cells have demonstrated safety and effectiveness, meaning they can combat these cancers without harming patients. This treatment shows promise, especially for cancers that are difficult to treat and have not responded well to other treatments. ^{1 3 4 5 6}

Who Is on the Research Team?

Scott M Norberg, D.O.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults 18+ with HPV-16-associated cancers (cervical, vulvar, vaginal, penile, anal, oropharyngeal) who've tried standard treatments or declined them. Must have proper liver and kidney function, acceptable blood counts, no more than three treated brain metastases. HIV negative and not on immunosuppressants except for certain exceptions.

Inclusion Criteria

I have either received or declined the first round of standard treatment.

My cancer is HPV-16 positive and can be measured.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have active infections, bleeding disorders, or severe heart, lung, or immune system diseases.

Any other condition, which would, in the opinion of the Principal Investigator, indicate that the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained

I am on immunosuppressive drugs, but not for minor local uses or as a reaction premedication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for imaging, heart and lung tests, and lab tests

Leukapheresis and Cell Engineering

Blood is removed, white blood cells are separated and genetically modified in the lab

1 week

1 visit for leukapheresis

Treatment

Participants receive chemotherapy drugs, E7 TCR cells, and injections to stimulate the cells

Up to 12 days

Inpatient stay for treatment administration

Initial Follow-up

Participants have a clinic visit about 40 days after cell infusion for physical exam, blood work, and scans

1 week

1 clinic visit

Long-term Follow-up

Participants are monitored for safety and effectiveness, with follow-up visits every 3 months for the first year, then every 6 months for up to 5 years, and as per PI discretion thereafter

15 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• E7 TCR cells

Trial Overview The trial tests E7 TCR cells therapy where patients' white blood cells are genetically modified to target cancer cells containing the HPV protein E7. It includes chemotherapy drugs Cyclophosphamide and Fludarabine followed by an infusion of these modified cells plus Aldesleukin shots to stimulate them.

How Is the Trial Designed?

Group I: Arm 2: Phase II Experimental Treatment 4 Interventions

1 x 10 e11 E7 Cells that was determined in Phase I + aldesleukin

Group II: Arm 1: Phase I Experimental Treatment 4 Interventions

Non-myeloablative, lymphocyte depleting preparative regimen, followed by E7 TCR Cells at escalating doses, followed by aldesleukin

E7 TCR cells is already approved in United States for the following indications:

Approved in United States as E7 TCR cells for:

• Human Papillomavirus-Associated Cancers
• Cervical cancer
• Oropharyngeal cancer
• Anal cancer
• Genital cancers

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

T cell-mediated adoptive immunotherapy targeting HPV16 proteins E6 and E7 shows promise as a safe and effective treatment for HPV-related cancers, particularly through the generation of MHC class II-restricted T cells.

The study successfully isolated a TCR specific to HPV16-E7 from a patient with a complete response, demonstrating that TCR gene transfer can produce sufficient numbers of functional T cells that can recognize and respond to HPV-infected cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and Characterization of an HLA-DRB1*04-Restricted HPV16-E7 T Cell Receptor for Cancer Immunotherapy. Mercier-Letondal, P., Marton, C., Deschamps, M., et al.[2019]

In a study involving 68 patients with HPV-associated cancers, researchers successfully reactivated and expanded T cells that specifically target HPV E6 and E7 proteins, achieving over a 1200-fold increase in T cell numbers from a significant portion of cervical and oropharyngeal cancer patients.

The presence of specific cytokines (IL-6, IL-7, IL-12, and IL-15) was crucial for the reactivation process, and the resulting T-cell lines showed promising characteristics for potential use in adoptive immunotherapy, indicating a scalable and compliant method for treating HPV16-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes for adoptive immunotherapy of HPV-associated malignancies. Ramos, CA., Narala, N., Vyas, GM., et al.[2021]

The study successfully isolated T cell receptor (TCR) genes from HPV16E7-specific T cell clones, demonstrating the feasibility of genetically engineering CD8+ T cells to express these TCRs for potential use in adoptive immunotherapy against cervical cancer.

Transgenic T cells showed effective recognition and response to HPV16E7-specific antigens, indicating that this approach could be a promising strategy for generating targeted T cell therapies for patients with cervical cancer and other HPV16-related cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer. Scholten, KB., Schreurs, MW., Ruizendaal, JJ., et al.[2010]

T cells engineered to target the HPV-16 E6 oncoprotein were able to specifically recognize and kill HPV-positive tumor cells, demonstrating their potential as an effective immunotherapy for HPV-associated cancers.

In a patient with metastatic anal cancer, the engineered T cells showed a significantly higher frequency of a specific T-cell clonotype in the tumor compared to peripheral blood, indicating a strong anti-tumor response that could be harnessed for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6. Draper, LM., Kwong, ML., Gros, A., et al.[2019]

TCR gene transfer can successfully generate HPV16 specific CD4+ T helper cells, which are crucial for effective immunotherapy against HPV-related cancers, as demonstrated through functional assays involving interferon-γ secretion and cytokine production.

The study shows that these engineered T cells can recognize specific HPV16 antigens presented by MHC molecules, indicating a promising approach for enhancing T cell responses in patients with cervical cancer and other HPV16-induced malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer. Scholten, KB., Turksma, AW., Ruizendaal, JJ., et al.[2021]

A high-avidity T cell receptor (TCR) targeting the HPV-16 E7 antigen was identified from a cervical biopsy, showing strong potential for treating HPV+ cancers due to its ability to specifically recognize and kill cancer cells.

In mouse models, T cells engineered to express this TCR successfully regressed established HPV-16+ cervical cancer tumors, paving the way for a clinical trial to evaluate this TCR gene therapy in patients with metastatic HPV+ cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. Jin, BY., Campbell, TE., Draper, LM., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9620481/

TCR-engineered T cells targeting E7 for patients with ... We have conducted a clinical trial of E7 TCR-T cells for patients with metastatic HPV-associated cancers (NCT02858310).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02858310

Study Details | NCT02858310 | E7 TCR T Cells for Human ... Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies including HPV-16+ cancers.

3. insight.jci.org insight.jci.org/articles/view/99488

Engineered T cells targeting E7 mediate regression of ... These results demonstrated that E7 TCR T cells could specifically engage and mediate T cell effector functions against HPV-16+ tumor lines. E7 ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT295681

KITE-439: A phase I study of HPV16 E7 T cell receptor- ... Preclinical efficacy has been observed with MHC class I-restricted T cell receptor (TCR)-engineered T cells targeting E7 on HPV16-positive tumor cells (Jin BY, ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.101

Safety and clinical activity of gene-engineered T-cell ... Conclusions: E7 TCR-T cells demonstrated safety and clinical activity in the treatment of highly refractory metastatic HPV-16+ cancers.

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/hpv-16-e7-tcr-expressing-t-cells?pn=1

Clinical Trials Using HPV-16 E7 TCR Expressing T-cells NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying hpv-16 e7 tcr expressing t-cells.