HPV Vaccine + M7824 for HPV-Associated Cancers

Overseen By Charalampos Floudas, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticonvulsants, Corticosteroids, Immunosuppressors, others

Disqualifiers: Active brain metastasis, Pregnancy, Recent major surgery, others

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 1 year

39 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests an HPV vaccine alone or with a drug called M7824. It targets adults with advanced HPV-related cancers or newly diagnosed stage II/III p16-positive oropharyngeal cancer. The vaccine helps the immune system recognize cancer cells, and M7824 makes it harder for these cells to hide from the immune system.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive drugs, you may need to stop them at least 1 to 4 weeks before joining the trial, depending on the duration of use.

What data supports the effectiveness of the treatment PRGN-2009 for HPV-associated cancers?

Research shows that PRGN-2009, a therapeutic vaccine, reduced tumor size and increased immune cells in mice with HPV-related tumors, suggesting it might help treat HPV-associated cancers by boosting the body's immune response. ^{1 2 3 4 5}

Is the HPV Vaccine + M7824 treatment generally safe for humans?

The safety of PRGN-2009, a therapeutic gorilla adenovirus HPV vaccine, has been evaluated in preclinical studies, showing promising results without reported toxicity in mice. However, specific human safety data for this treatment combination is not provided in the available research. ^{1 2 3 6 7}

How is the treatment PRGN-2009 AdenoVerse Immunotherapy different from other treatments for HPV-associated cancers?

PRGN-2009 AdenoVerse Immunotherapy is unique because it is a therapeutic vaccine using a gorilla adenovirus to target HPV-associated cancers by inducing a strong immune response against the E6 and E7 proteins of HPV, which are crucial for cancer development. Unlike existing prophylactic vaccines that prevent HPV infection, PRGN-2009 aims to treat established HPV-related cancers by enhancing the body's immune system to attack cancer cells. ^{1 2 3 5 8}

Research Team

Charalampos Floudas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults (18+) with advanced or metastatic HPV-associated cancers, including cervical, anal, and p16-positive oropharyngeal cancers. Participants must have measurable disease and an ECOG performance status of <=2. Prior treatments are allowed under specific conditions. Adequate organ function is required, and effective contraception must be used.

Inclusion Criteria

My kidney and liver are functioning well.

My liver enzymes are within the required range for the trial.

My throat cancer is p16 positive.

Exclusion Criteria

I am in a trial where starting treatment after diagnosis could take more than 70 days.

I haven't had major surgery in the last 28 days.

I have an autoimmune disease that could worsen with certain treatments, except for some.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive the HPV vaccine alone or with M7824. Phase I participants receive the vaccine 2-3 times in the first month, then a booster every 4 weeks. M7824 is given every 2 weeks. Phase II participants receive two doses of the vaccine two weeks apart before planned chemoradiation or surgery.

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment. A visit occurs within 4 weeks after stopping treatment, followed by annual long-term follow-up.

Lifetime

1 visit (in-person) within 4 weeks, annual follow-up (virtual)

Treatment Details

Interventions

• PRGN-2009
• PRGN-2009, M7824

Trial Overview The trial tests the safety and immune response to an HPV vaccine alone or combined with M7824 in patients with HPV-related cancers. Phase I involves multiple vaccine doses plus bi-weekly M7824 infusions for up to a year; Phase II precedes chemoradiation/surgery with two vaccine doses alone or with M7824.

Participant Groups

Group I: 4/Arm 2B Experimental Treatment 8 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg given as neoadjuvant or induction therapy.

Group II: 3/Arm 2A Experimental Treatment 8 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) given as neoadjuvant or induction therapy.

Group III: 2/Arm 1B Experimental Treatment 8 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at recommended phase 2 dose (RP2D) plus M7824 at 1200 mg.

Group IV: 1/Arm 1A Experimental Treatment 7 Interventions

Human Papillomavirus Vaccine (HPV) vaccine at 1x10(11) Viral Particles (VP) Dose Level 1 (DL1) and at 5x10(11) VP Dose Level 2 (DL2)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

HPV-related cancers, including cervical and head and neck cancers, account for a significant portion of global cancer cases, highlighting the urgent need for effective vaccination strategies, especially since over 80% of people are exposed to HPV by age 50.

While prophylactic vaccines like Gardasil® and Cervarix® have successfully reduced HPV infections in young populations, there are currently no FDA-approved therapeutic vaccines for those already infected, indicating a critical gap in treatment options for HPV-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Vaccines for HPV-Associated Malignancies. Smalley Rumfield, C., Roller, N., Pellom, ST., et al.[2020]

In a first-in-human phase 1 study involving adult patients with severe recurrent respiratory papillomatosis (RRP), the immune-therapeutic PRGN-2012 showed a promising 50% complete response rate at the highest dose, indicating its potential efficacy in enhancing HPV-specific T cell immunity.

The study found that responders to PRGN-2012 had a distinct immune profile, including greater expansion of HPV-specific T cells and lower papilloma HPV gene expression, suggesting that these factors may influence the effectiveness of the treatment and the tumor microenvironment's response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tumor microenvironment state associates with response to HPV therapeutic vaccination in patients with respiratory papillomatosis. Norberg, SM., Bai, K., Sievers, C., et al.[2023]

A comprehensive analysis of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) identified 3,112 AEs for Cervarix, 31,606 for Gardasil, and 6,872 for Gardasil 9, highlighting the need for ongoing monitoring of vaccine safety.

The study found 46 unique serious adverse events (SAEs) associated with the HPV vaccines, clustered around behavioral, neurological, immune, nervous, and reproductive systems, indicating that while the vaccines are effective, further research is needed to understand the cause-and-effect relationships of these AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. Zi, W., Yang, Q., Su, J., et al.[2022]

References

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

Characterization of recombinant gorilla adenovirus HPV therapeutic vaccine PRGN-2009. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Therapeutic Vaccines for HPV-Associated Malignancies. [2020]

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

The tumor microenvironment state associates with response to HPV therapeutic vaccination in patients with respiratory papillomatosis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Preventative and therapeutic vaccines for cervical cancer. [2007]

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

OAE-based data mining and modeling analysis of adverse events associated with three licensed HPV vaccines. [2022]

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

Post-marketing surveillance study of the safety of the HPV-16/18 vaccine in Korea (2017-2021). [2023]

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

Vaccines against human papillomavirus. [2019]