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

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This healthy related donor clinical trial is linked to a recipient clinical trial protocol for therapeutic purposes. In this healthy donor protocol, haploidentical relatives of a patient with recurrent or metastatic human papilloma virus (R/M HPV) 16-associated malignancy will be invited to be vaccinated with a therapeutic HPV vaccine series (PVX1) to generate HPV-specific white blood cells. In the linked recipient phase 1 clinical trial protocol, patient with incurable, locally recurrent or metastatic HPV 16-associated head and neck cancer will be randomized to one of two arms: Arm A: non-myeloablative (NMA) allogeneic bone marrow transplant (alloBMT) OR Arm B: CD8-depleted donor lymphocyte infusion (DLI) on Day 0 of a dose escalation scheme These two clinical trials are separated so that the healthy donor trial deals exclusively with issues of safety and immunological efficacy of the HPV vaccine series and this companion recipient trial examines the safety, feasibility and clinically efficacy of the allogeneic bone marrow graft and CD8-depleted DLI. The central hypothesis of the clinical trial is that patients with R/M HPV-associated malignancies can be safely and effectively treated by allogeneic bone marrow transplantation and/or CD8-depleted DLI from a healthy related donor that has been vaccinated against HPV16 E6 and E7 proteins.

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.

What data supports the effectiveness of this treatment for HPV-related cancers?

Research shows that the combination of pNGVL4a-Sig/E7(detox)/HSP70 and TA-HPV vaccines can generate strong immune responses in mice, leading to better control of HPV-related tumors and longer survival. This suggests that the treatment may be effective in managing HPV-associated diseases in humans. ^{1 2 3 4 5}

How is the HPV Vaccine Combination for Cancer treatment different from other treatments?

This treatment is unique because it combines a DNA vaccine, pNGVL4a-Sig/E7(Detox)/HSP70, with a viral vector vaccine, TA-HPV, to enhance the immune response against HPV-related cancers. The combination uses a 'prime-boost' strategy, where the DNA vaccine is given first to prime the immune system, followed by the TA-HPV vaccine to boost the response, potentially leading to stronger and more effective antitumor immunity. ^{2 5 6 7 8}

Research Team

Tanguy Seiwert, M.D.

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

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

I am generally healthy with no significant medical issues.

Lymphocyte number ≥ 500

Absolute neutrophil count ≥ 1,000

Exclusion Criteria

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

History or presence of atopic dermatitis

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. England 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. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of a human papillomavirus type 16 E7 bacterial exotoxin fusion protein adjuvanted with CpG or GPI-0100 in a preclinical mouse model for HPV-associated disease. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The promise of combining cancer vaccine and checkpoint blockade for treating HPV-related cancer. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

A phase II study of Hsp-7 (SGN-00101) in women with high-grade cervical intraepithelial neoplasia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Epithelial boost enhances antigen expression by vaccinia virus for the generation of potent CD8+ T cell-mediated antitumor immunity following DNA priming vaccination. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals. [2009]

7. Netherlands 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Technology evaluation: T-cell activator, Xenova. [2019]