HPV Cancer Resources

Helpful Information for Parents, Patients, Partners, and Providers

Helpful Information for Parents, Patients, Partners, and Providers

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Clinical Trials Focused on Recurrent and Metastatic Disease

MEDICAL DISCLAIMER

Just to be clear: I am NOT a doctor. The information contained in this website is NOT intended as a recommendation for the self management of health problems, medical conditions, or wellness. It is not intended to endorse or recommend any particular type of medical treatment, physician, or treatment facility. Should any reader have any health care related questions, I strongly suggest you call or consult your physician or healthcare provider before looking into other things on the internet. The information contained in this website should NOT be used by any reader to disregard medical and/or health related advice or provide a basis to delay consultation with a physician or a qualified healthcare provider. HPV Cancer Resources disclaims any liability based on information provided in this website.



This page is for those who have experienced either recurrent or metastatic disease (i.e. cancer that has spread to other organs). In the case of HPV+ head and neck cancers, about 5 to 10% of patients are not successfully treated with standard surgery and/or chemotherapy/radiation treatments. Either the cancer reappears in the head and neck regions, or it is found in other organs. Although the lung is the most common distant site involved in both HPV+ and HPV- disease, the HPV+ patients get metastases to several locations that are atypical for head and neck squamous cell carcinoma, including the brain, kidney, skin, skeletal muscle, axillary lymph nodes, and the intra-abdominal lymph nodes.

If conventional treatments are not appropriate for treating these patients (or if they don’t work), then a clinical trial of a new treatment is often the next step. The good news is that there are a lot of them available for head and neck cancer patients. Most of should be available to those who have HPV+ cancers. The graphic below, though complicated, should give you (or your doctors) a feel for the many different types of trials that are being tested. The reason that there are so many trials going now is because of both commercial and medical issues. There’s been a huge push into immunotherapy treatments over the past few years as certain treatments, such as checkpoint inhibitors (e.g. Keytruda; Opdivo), have gone mainstream. Many different immunotherapy approaches are being tried, and there is simply no way to know, in advance of doing the trials, which ones are most likely to work. Clinical evidence will emerge slowly as the trials are completed and the results are carefully analyzed. This may take a considerable period of time since the ultimate measure of success is long term patient survival.

Nearly 200 Clinical Immunotherapy Trials for Head and Neck Cancer

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Source: Horton, J.D. et al Immune Evasion by Head and Neck Cancer: Foundations for Combination Therapy. Trends in Cancer, April 2019, Vol. 5, No. 4 https://doi.org/10.1016/j.trecan.2019.02.007

You will have to discuss with your doctors which trials you might be eligible for. Some may require you to relocate to a distant city to participate. Look at my Clinical Trial Basics page for more general information about that. One area that I want to focus on is clinical trials that are specifically targeting the HPV virus itself. The idea is that if HPV is responsible for causing the cancer, then attacking HPV DNA or proteins in cells might have a good chance of knocking the cancer out. Let me be absolutely clear about one thing: attacking HPV as the target may or may not be more successful than any of the other types of treatment approaches depicted in the graphic above. There is simply no way to know this. One possible advantage for the cancer field in general of these HPV targeted treatments is that they may, IF they are successful, be useful for treating ALL of the HPV-caused cancers. Thus, they may work in treating cervical, vaginal, vulval, penile, and anal cancers in addition to working on HPV+ head and neck cancers. The list below shows some of these treatments being targeted against head and neck cancers, along with some other targets in these same cancers. However, there are other HPV-focused clinical trials that are being conducted on other cancers (e.g. cervical cancer) and do not appear in the table below. Again, if one of these treatments is successful against cervical or one of the other HPV-caused cancers, then there is a reasonable chance that it would have some efficacy against head and neck cancers as well. These types of treatments are often referred to by doctors as being pan-specific or tissue agnostic. That’s just a fancy way of saying that they should work in any tumor that’s caused by HPV. Sounds good, right? One treatment for six cancers.

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Source: Wang, C. et al Targeting Head and Neck Cancer by Vaccination. Front. Immunol. 9:830 (2018) doi: 10.3389/ mmu.2018.00830

Below are some descriptions of clinical trials (not necessarily currently focused on head and neck cancers) that are specifically targeting HPV. This list may be out of date, and any particular trial may have been completed (or abandoned) by the time you read this. The best way to confirm that is to go to the ClinicalTrials.gov website and used the identifier number for the trial to find out the current status. Note that this database is not always up to date either, so if you see a trial of interest, have your doctor contact the clinical coordinator listed on the ClinicalTrials.gov trial page. Even if these trials are no longer accepting patients, they may be about to open up for patients with similar cancers. That’s why it’s valuable to look at trials for cervical or anal cancer, for example. Success in those clinical trials with an agent targeting HPV may result in expansion to other tissues e.g. head and neck cancers.

This is intended to give a feel for clinical trials in this area. It is NOT intended to be a complete list:

ClinicalTrials.gov identifier: NCT03912831

FOCUS OF THE THERAPY: CAR-T immunotherapy directed against the E7 protein of HPV. CAR-T trials have shown remarkable success in other indications (e.g. lymphoma) but have also been associated with very serious side effects.

HOW IT WORKS: Your blood is drawn and the T cells in that blood are purified. They are then genetically modified to target them against a protein made by HPV. The T cells are supposed to kill off all of the HPV infected cells, thereby eliminating the cancer. The exact protocol features cyclophosphamide plus fludarabine chemo followed by KITE-439 (targets the E7 encoded protein of HPV) in HLA-A*02:01 adults.

DISEASE TARGETED: Relapsed/refractory HPV 16+ cancers, type not specified

WHERE BEING CONDUCTED: City of Hope Medical Center, Duarte, CA; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, and University of Chicago Medical Center.

TRIAL STATUS (as of 2019): Recruiting

TRIAL SPONSOR: Kite Pharmaceuticals (Gilead)
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ClinicalTrials.gov identifier: NCT01022346

FOCUS OF THE THERAPY: Immunotherapy: Infuses a protein that activates an immune system response to combat high-risk HPV lesions.

HOW IT WORKS: The modified vaccinia virus Ankara (MVA) is a highly attenuated replication-deficient strain of vaccinia virus used widely as a gene-delivery system of vaccines. Tipapkinogen Sovacivec (TS) has inserted genes that code for three proteins: human cytokine IL-2, and modified forms of HPV 16 E6 and E7 proteins that have been rendered non oncogenic. MVA by itself contributes to the immune reaction by the induction of an Interferon-alpha response. Upon sub-cutaneous injection, TS infects the surrounding cells. The expressed HPV16 E6 and E7 proteins are then processed and presented by dendritic cells that are co-activated by the viral infection. These dendritic cells migrate to the draining lymph-node and present E6 and E7 peptides to the naive T-cells present in the lymph-node, which should allow development of a targeted cell mediated immune response.

DISEASE TARGETED: High Grade Cervical Intraepithelial Neoplasia Grade 2 or 3 Associated With High Risk HPV Infection

WHERE BEING CONDUCTED: 66 locations

TRIAL SPONSOR: Hoffmann-La Roche

TRIAL STATUS (as of 2019): Completed

REFERENCE: Harper, D.M. et al. The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up. Gynecologic Oncology 153, 521-529 (2019). FREE Download
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ClinicalTrials.gov identifier: NCT03721978

FOCUS OF THE THERAPY: Immunotherapy: Infuses a protein that activates an immune system response to combat high-risk HPV lesions.

HOW IT WORKS: VGX-3100 is a DNA-based immunotherapy under investigation for the treatment of HPV 16 and HPV 18 infection and pre-cancerous lesions of the cervix (Phase 3) and vulva and anus (Phase 2). VGX-3100 has the potential to be the first approved treatment for HPV infection of the cervix and the first non-surgical treatment for precancerous cervical lesions. VGX-3100 works by stimulating a specific immune response to HPV-16 and HPV-18, which targets the infection and causes destruction of precancerous cells. In a randomized, double-blind, placebo-controlled Phase 2b study in 167 adult women with histologically documented HPV 16/18 cervical HSIL (CIN2/3), treatment with VGX-3100 resulted in a statistically significantly greater decrease in cervical HSIL and clearance of HPV infection vs. placebo. The most common side effect was injection site pain, and no serious adverse events were reported. VGX-3100 utilizes the patient's own immune system to clear HPV 16 and HPV 18 infection and precancerous lesions without the increased risks associated with surgery, such as loss of reproductive health and negative psychosocial impacts.

AGENTS USED: VGX-3100, a synthetic vaccine designed to raise immune responses against the E6 and E7 oncogenes associated with HPV types 16 and 18, i.e., it targets four antigens. These oncogenes are responsible for transforming HPV-infected cells into precancerous and cancerous cells. The goal is to stimulate a T-cell immune response strong enough to cause the rejection of these infected or transformed cells. The potential of such a therapeutic vaccine would be to treat precancerous dysplasias (cervical intraepithelial neoplasias or CINs), cervical cancers, as well as other cancers caused by these HPV types such as head and neck and anogenital cancers.

DISEASE TARGETED: Cervical cancer precursor

WHERE BEING CONDUCTED: Ten sites in the US

TRIAL STATUS (as of 2019): Recruiting

TRIAL SPONSOR: Inovio Pharmaceuticals, Inc.
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ClinicalTrials.gov identifier: NCT02411019

FOCUS OF THE THERAPY: This is a follow-up study to investigate the change of immunogenicity and lesion condition in subjects with cervical intraepithelial neoplasia (CIN) 3 who have enrolled and participated GX-188E phase II trial (GX-188E_CIN3_P2).

HOW IT WORKS: In phase II study, 72 patients were assigned to two dose groups (1mg and 4mg) and were administered three times with GX-188E by electroporation during an entire period of study. After the final administration, the follow-up will be conducted to investigate safety and efficacy aspects.

AGENTS USED: GX-188E, a synthetic vaccine. Details about the vaccine are murky. The potential of such a therapeutic vaccine would be to treat precancerous dysplasias (cervical intraepithelial neoplasias or CINs), cervical cancers, as well as other cancers caused by these HPV types such as head and neck and anogenital cancers. Results from a phase II study have been presented.

DISEASE TARGETED: Cervical cancer precursor

WHERE BEING CONDUCTED: Several sites in Korea

TRIAL STATUS (as of 2019): Recruiting

TRIAL SPONSOR: Genexine, a Korean biotechnology company
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ClinicalTrials.gov identifier: NCT03057912

FOCUS OF THE THERAPY: A Safety and Efficacy Study of TALEN and CRISPR/Cas9 in the Treatment of HPV-related Cervical Intraepithelial Neoplasia

HOW IT WORKS: HPV persistent infection is the major causal factor of cervical intraepithelial neoplasia (CIN) and cervical cancer. The important roles of E6 and E7 playing in HPV-driven carcinogenesis make them attractive targets for therapeutic interventions. Previous evidences showed that using designated TALEN and CRISPR/Cas9 as genome editing tool could produce disruption of HPV16 and HPV18 E6/E7 DNA, significantly decreasing the expression of E6/E7, inducing cell apoptosis and inhibiting cell lines growth.
This study will evaluate the safety and efficacy of TALEN-HPV E6/E7 and CRISPR/Cas9-HPV E6/E7 in treating HPV Persistency and HPV-related Cervical Intraepithelial Neoplasia

AGENTS USED: Gene modifying therapies TALEN and CRISPR

WHERE BEING CONDUCTED: The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

TRIAL STATUS (as of 2019): Not yet recruiting

TRIAL SPONSOR: Hu Zheng, First Affiliated Hospital, Sun Yat-Sen University
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ClinicalTrials.gov identifier: NCT03162224

FOCUS OF THE THERAPY: Combination immunotherapy

HOW IT WORKS: MEDI0457 (previously called INO-3112) is an investigational immunotherapy being developed to treat human papillomavirus (HPV)-positive cervical cancer and head and neck cancer. It was originally developed by Inovio, but MedImmune, which is part of AstraZeneca, acquired exclusive rights to the drug in August 2015. MEDI0457 is a DNA-based cancer vaccine with two main components produced using Inovio’s proprietary SynCon technology. Those components are VGX-3100, a DNA plasmid containing modified sequences for E6 and E7, and INO-9012, a DNA plasmid containing the immune activator IL-12. Plasmids are pieces of circular DNA that contain the sequences necessary to promote the expression of a certain gene.
MEDI0457 is injected into the patient’s muscle and enters the cells after electroporation treatment carried out by Inovio’s Cellectra delivery device. Electroporation is the application of a small electrical pulse. When E6 and E7 are expressed from VGX-3100, the immune system recognizes these proteins as antigens, or foreign substances associated with an infection or disease. This triggers the production of cytotoxic T lymphocytes (CTLs), or “killer” T-cells. CTLs are a type of immune cell that can identify and destroy cells expressing a particular antigen, in this case, the HPV-infected tumor cells. The expression of IL-12 will boost the immune response produced by VGX-3100 as it stimulates the production of CTLs, increasing the potential for tumor cell death.

AGENTS USED: MEDIO457 (also known as INO 3112), an HPV DNA vaccine, plus checkpoint inhibitor durvalumab (mAb against PL-L1). MEDI0457 administration by IM injection followed by electroporation (EP) using CELLECTRA®5P device.

DISEASE TARGETED: Head and neck cancer

WHERE BEING CONDUCTED: 23 locations

TRIAL STATUS (as of 2019): Active, not recruiting

TRIAL SPONSOR: MedImmune
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ClinicalTrials.gov identifier: NCT03578406

FOCUS OF THE THERAPY: Two-Arm Open-Labeled Trial of HPV-E6-Specific TCR-T Cells With or Without Anti-PD1 Auto-secreted Element in the Treatment of HPV-Positive Head and Neck Carcinoma or Cervical Cancer

HOW IT WORKS: T cell therapy administered with or without a PD-1 (checkpoint) inhibitor

AGENTS USED: Patients were infused with HPV E6-specific TCR-T cells

DISEASE TARGETED: Head and neck cancer; cervical cancer

WHERE BEING CONDUCTED: Chongqing , China

TRIAL STATUS (as of 2019): Not specified

TRIAL SPONSOR: Xinqiao Hospital of Chongqing, TCRCure Biotech Co., Ltd

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ClinicalTrials.gov identifier: NCT04180215

FOCUS OF THE THERAPY: Phase 1/2 clinical trial of HB-201, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers. HB-201 is an arenavirus vector-based vaccine expressing the inactivated fusion protein HPV 16 E7E6. This is a first in human (FIH) Phase I/II, multinational, multicenter, open-label study of HB-201 monotherapy or in combination with an immune checkpoint inhibitor in HPV 16+ confirmed cancers that consists of 2 parts: Phase I Dose Escalation and Phase II Dose Expansion.

HB-201 is a TheraT® platform-based vector (replication attenuated) from the arenavirus family expressing a non-oncogenic, but highly antigenic E6/E7 fusion protein from HPV16.

HOW IT WORKS: Induces T cell anti-tumor responses

AGENTS USED: HB-201, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers.

DISEASE TARGETED: HPV+ advanced, metastatic, or recurrent head and neck cancer; other HPV+ cancers

WHERE BEING CONDUCTED: Not specified

TRIAL STATUS (as of 2019): Phase 1/2 clinical trial started Dec. 30, 2019

TRIAL SPONSOR: HOOKIPA Biotech of Austria. Principal Investigator is Igor Matushansky, MD, PhD

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ClinicalTrials.gov identifier: NCT02865135

FOCUS OF THE THERAPY: A Phase Ib/II Trial To Test The Safety And Efficacy Of Vaccination With HPV16-E711-19 Nanomer For The Treatment Of Incurable HPV 16-Related Oropharyngeal, Cervical And Anal Cancer In HLA-A*02 Positive Patients

HOW IT WORKS: Induces T cell anti-tumor responses

AGENTS USED: DPX-E7, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers.

DISEASE TARGETED: HPV+ advanced, metastatic, or recurrent head and neck cancer; anal, and cervical HPV+ cancers

WHERE BEING CONDUCTED: Not specified

TRIAL STATUS (as of 2019): Phase 1/2 clinical trial

TRIAL SPONSOR: IMV Inc. and Dana Farber Cancer Center

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ClinicalTrials.gov identifier: NCT03978689

FOCUS OF THE THERAPY: CUE-101 is a novel fusion protein designed to activate and expand a population of tumor specific T cells to eradicate human papilloma virus (HPV)-driven malignancies. HPV causes multiple tumor types including cervical, head and neck squamous cell carcinoma (HNSCC) and anal cancers. Initial testing of CUE-101 will be conducted in HPV16+ HNSCC patients. The primary objectives of the first-in-human trial are to assess the safety and tolerability of CUE-101 in subjects with recurrent/metastatic HNSCC and to determine the maximum tolerated dose or recommended Phase 2 dose based on markers of biological activity. Pharmacokinetics (PK), antitumor immune response, preliminary antitumor activity and the potential for immunogenicity will also be assessed. This will be an open-label multicenter phase I trial conducted in the U.S. involving approximately 50 patients.

HOW IT WORKS: Induces T cell anti-tumor responses

AGENTS USED: CUE-101, an immunotherapy for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers.

DISEASE TARGETED: HPV Positive Oropharyngeal Squamous Cell Carcinoma

WHERE BEING CONDUCTED: Numerous locations across the US

TRIAL STATUS (as of 2020): Phase 1 clinical trial

TRIAL SPONSOR: Cue Biopharma


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ClinicalTrials.gov identifier: NCT02379520

FOCUS OF THE THERAPY: Study evaluating HPV-16/18 E6/E7-Specific T Lymphocytes in patients with Relapsed HPV-Associated Cancers. Tessa’s TT12 is an autologous T cell therapy product composed of HPVSTs that have been trained to target HPV 16/18 antigens and genetically modified with a decoy TGF-β receptor to overcome the immuno-suppressive tumor microenvironment.The safety and optimal dose selection of armored HPVSTs in combination with an anti-PD-1 antibody is currently being evaluated in an ongoing investigator-sponsored Phase 1 trial (NTC02379520) in the United States, in patients with relapsed/resistant HPV-associated cancers.

In collaboration with MSD (tradename of Merck & Co., Inc., Kenilworth, N.J., USA), Tessa will conduct a separate, multi-center Phase 1b/2 trial to evaluate the safety and efficacy of our autologous HPVST therapy in combination with MSD’s anti-programmed death receptor-1 (PD-1) antibody, Pembrolizumab (KEYTRUDA®), following pre-conditioning lymphodepletion chemotherapy, in patients with recurrent/refractory or metastatic HPV 16/18-positive cervical cancer.

HOW IT WORKS: Induces T cell anti-tumor responses.

AGENTS USED: TT12 is an autologous T cell therapy product

DISEASE TARGETED: HPV Positive cancers (all types)

WHERE BEING CONDUCTED: Baylor College of Medicine, Texas
Contact: Carlos Ramos, MD 832-824-4817 caramos@bcm.edu
Contact: Vicky Torrano, RN 832-824-7821 vtorrano@bcm.edu

TRIAL STATUS (as of 2020): Phase 1 clinical trial

TRIAL SPONSOR: Tessa Therapeutics Singapore

Personalized Cancer Vaccines in Clinical Trials


This new approach is also an immunotherapy, but the targets (the molecules expressed on the cancer cells that we want the immune system to attack) are personalized for each tumor. Put another way, each cancer vaccine is an individual treatment designed only for that one person. The hope is that by customizing the vaccine it will lead to the most efficacious treatment possible. Various techniques are being used to generate these vaccines.

A basic version of this process is shown in the graphic below, illustrating how tumor cells are removed and used to create the vaccine. Neoantigens are novel proteins not normally found in the body, and therefore they make good targets for immunotherapy treatments.
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You can read more about this basic concept in this article by Jasreet Hundal and Elaine Mardis Personalized Cancer Vaccines in Clinical Trials, published in The Scientist in July 2019.The article includes a more complete version of the Table below with individual trial listings. Ask your doctor if you are interested in participating in one of these trials.

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CRISPR (pre-clinical)

I just wanted to throw this in to the mix even though this technique is not ready yet for the clinic. In short, a gene therapy approach called CRISPR may someday be useful in treating HPV cancers. CRISPR is a technique that can specifically target HPV within tumor cells. A recent paper showed that CRISPR in a mouse cancer model was effective at eliminating HPV caused tumors. It’s not ready for prime time for this purpose, but the CRISPR technique is just starting to be used for other clinical trials, and is thought to have great potential. I’ll keep an eye on this and update the page should this actually move forward into the clinic. In the meantime, here’s a link to the mouse paper:

Jubair, L et al Systemic Delivery of CRISPR/Cas9 targeting HPV oncogenes is effective at eliminating established tumors. Molecular Therapy (published online Aug. 2019)