HPV Vaccine Combination for Cancer

(J21112LINKED Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Heart disease, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and effectiveness of an HPV vaccine in generating specific immune cells in healthy relatives of patients with advanced head and neck cancer linked to HPV 16. The trial will examine two treatment paths: a bone marrow transplant or a special type of cell infusion from the vaccinated relative. Suitable candidates for this trial are healthy relatives of patients with advanced HPV 16-related cancer who have not received an HPV vaccine other than standard ones like Gardasil or Cervarix. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs or have had recent chemotherapy, radiation, or biological cancer therapy, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the pNGVL4a-Sig/E7(Detox)/HSP70 treatment is generally well-tolerated. In a study with 12 participants, researchers reported no serious side effects. Some minor side effects occurred, but they were not severe, suggesting the treatment is safe enough for further testing.

For the TA-HPV vaccine, the safety data is even more reassuring. Over 160 studies indicate that HPV vaccines, like TA-HPV, have a strong safety record. They have been used for many years with few serious side effects. The most common reactions are mild, such as soreness at the injection site or a mild fever.

Both treatments appear safe based on current data. However, since this is an early phase trial, ongoing research remains crucial to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HPV-related cancers because they represent a novel approach to boosting the immune system's response against cancer cells. Unlike traditional treatments, like surgery, radiation, and chemotherapy, which directly target and destroy cancer cells, these investigational vaccines—pNGVL4a-Sig/E7(Detox)/HSP70 and TA-HPV—aim to train the body's immune system to recognize and attack cancer cells more effectively. The vaccines work by targeting specific HPV antigens, potentially leading to a more precise and durable immune response. This could mean fewer side effects compared to conventional therapies, offering a more targeted and potentially more effective way to treat HPV-related cancers.

What evidence suggests that this trial's treatments could be effective for HPV-associated malignancies?

Research shows that the pNGVL4a-Sig/E7(Detox)/HSP70 vaccine, a treatment in this trial, can boost the body's defense against HPV16, a virus linked to certain cancers. This vaccine encourages the production of white blood cells that specifically target and fight HPV16. Early results suggest it could enhance the body's ability to combat the E6 and E7 proteins of HPV16, often found in cancer cells.

Regarding the TA-HPV vaccine, another treatment option in this trial, studies have shown that vaccines targeting HPV can effectively prevent diseases caused by the virus. Although TA-HPV is still being tested, similar vaccines have successfully reduced the risk of HPV-related cancers. Overall, both vaccines in this trial show promise in fighting cancers related to HPV, especially those caused by the HPV16 type. ^{6 7 8 9 10}

Who Is on the Research Team?

Tanguy Seiwert, M.D.

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for healthy relatives of patients with recurrent or metastatic HPV 16-related cancers. Participants must be haploidentical to the patient and willing to receive an HPV vaccine series to help generate specific white blood cells.

Inclusion Criteria

Lymphocyte number ≥ 500

Absolute neutrophil count ≥ 1,000

Platelets ≥ 90,000

Exclusion Criteria

I have not had any cancer except for nonmelanoma skin cancer in the last 5 years.

I do not have an active or chronic HIV, HCV, or HBV infection.

History or presence of atopic dermatitis

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive a series of vaccines including pNGVL4a-Sig/E7(Detox)/HSP70 and TA-HPV to generate HPV-specific white blood cells

3 months

Multiple visits for vaccine administration

Blood and Bone Marrow Collection

Collection of peripheral blood or bone marrow for use in recipient's treatment

1-2 weeks

1 visit for collection

Follow-up

Participants are monitored for safety and effectiveness after vaccination

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• pNGVL4a-Sig/E7(Detox)/HSP70
• TA-HPV

Trial Overview The study tests a therapeutic HPV vaccine series on healthy donors, who are relatives of cancer patients, to see if it's safe and can stimulate an immune response. The linked recipient trial then uses these vaccinated donor cells in two different treatment approaches for the cancer patients.

How Is the Trial Designed?

Group I: Blood Donation Only for Recipient's CD-8 Depleted DLI Active Control 1 Intervention

Donor patients receive the vaccination series followed by collection of peripheral blood. This blood will be used to create the CD8-depleted donor lymphocyte infusion (DLI) which will be given to the donor's related recipient patient on the J21112 study.

Group II: Blood and Bone Marrow Donation for Recipient Patient's alloBMT Active Control 1 Intervention

Donor patients receive the vaccination series. This will be followed by a bone marrow harvest under anesthesia that will be given to the donor's related recipient patient on the J21112 study. Then, depending on recipient response to allogeneic BMT, donor may return for collection of peripheral blood used to create CD8-depleted donor lymphocyte infusion (DLI) which will be given to the donor's related recipient patient on D90.

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

PapiVax Biotech, Inc.

Collaborator

Trials

6

Recruited

120+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The combination of tipapkinogene sovacivec (TG4001) and avelumab was found to be safe for HPV16+ cancer patients, with no dose-limiting toxicities reported and most treatment-related adverse events being mild (grade 1/2).

In this study involving 43 heavily pretreated patients, the overall response rate was 22%, with a median overall survival of 11 months, indicating that this treatment can provide antitumor activity even in advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib/II trial of tipapkinogene sovacivec, a therapeutic human papillomavirus16-vaccine, in combination with avelumab in patients with advanced human papillomavirus16-positive cancers. Borcoman, E., Lalanne, A., Delord, JP., et al.[2023]

The DNA vaccine encoding E7/HSP70 significantly increased E7-specific CD8+ T cell precursors and showed strong antitumor effects against HPV-16 expressing tumors in mice, indicating its potential for cancer immunotherapy.

Administering the DNA vaccine via a gene gun was found to be the most effective method, generating the highest number of E7-specific T cells and requiring a lower dose for similar or better antitumor effects compared to other administration methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the CD8+ T cell responses and antitumor effects generated by DNA vaccine administered through gene gun, biojector, and syringe. Trimble, C., Lin, CT., Hung, CF., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12472360/

Global Burden and Incidence Trends in Cancers Associated ... It has been proven that the HPV vaccine is effective against HPV infection and disease in males [26], but only 7.0% of males have received the ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS6118

Phase II trial assessing safety, efficacy and immune ... There is a 90% overall survival for HPV+/p16+ OPSCC (40% for HPV-/p16- OPSCC), which can be cured with multimodality care. For patients with R/M ...

3. cdc.gov cdc.gov/united-states-cancer-statistics/publications/hpv-associated-cancers.html

Cancers Associated with Human Papillomavirus Of these, we estimated that 35,000 cancers could have been prevented by the 9-valent HPV vaccine, including 30,700 caused by HPV types 16 and 18 ...

4. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-025-06470-x

Human papilloma virus (HPV) mediated cancers: an insightful ... This review aims to provide a comprehensive overview of the recent advances in HPV-related cancer biology and epidemiology.

5. nature.com nature.com/articles/s41392-024-02083-w

Roles of human papillomavirus in cancers: oncogenic ... Research has confirmed that HPV-positive OPSCC is more sensitive to radiotherapy and chemotherapy, with a less aggressive phenotype and better ...

6. cdc.gov cdc.gov/vaccine-safety/vaccines/hpv.html

Human Papillomavirus (HPV) Vaccine Safety HPV vaccines are safe​​ Findings from many vaccine safety monitoring systems and more than 160 studies have shown that HPV vaccines have a favorable safety ...

7. cdc.gov cdc.gov/hpv/hcp/vaccination-considerations/safety-and-effectiveness-data.html

HPV Vaccine Safety and Effectiveness Data More than 15 years of monitoring and research have accumulated reassuring evidence that HPV vaccination provides safe, effective, and long-lasting protection.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4964727/

Quadrivalent HPV vaccine safety review and safety monitoring ... Safety of each HPV vaccine was studied extensively in pre-licensure clinical trials. 18,083 males and females were included in the 4vHPV clinical trials, 23,952 ...

9. who.int who.int/groups/global-advisory-committee-on-vaccine-safety/topics/human-papillomavirus-vaccines/safety

Safety of HPV vaccines The risk of anaphylaxis has been characterized as approximately 1.7 cases per million doses, and syncope was established as a common anxiety or stress-related ...

10. aacrjournals.org aacrjournals.org/clincancerres/article/8/12/3676/199740/Safety-and-Immunogenicity-of-TA-HPV-a-Recombinant

Safety and Immunogenicity of TA-HPV, a Recombinant ... The study confirms that outpatient vaccination with TA-HPV is feasible, safe, and associated with little toxicity. Our results show that vaccination with TA-HPV ...