HPV Vaccine + M7824 for HPV-Associated Cancers

NR
CF
Overseen ByCharalampos Floudas, M.D.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether an HPV vaccine combined with the drug M7824 (also known as PRGN-2009 AdenoVerse Immunotherapy) can effectively treat certain cancers linked to the human papillomavirus (HPV). The researchers aim to find a safe dose and determine if the combination treatment elicits a stronger immune response than the vaccine or drug alone. Those who might benefit from joining include individuals with advanced HPV-related cancers or specific types of oropharyngeal (throat) cancer planning for major treatment. Participants will receive either the HPV vaccine alone or with M7824, with treatment lasting up to a year. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

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

Research has shown that the HPV vaccine PRGN-2009 and the drug M7824 have been tested for safety in people with HPV-related cancers. Early results suggest that PRGN-2009, whether used alone or with another experimental drug, is generally safe and well-tolerated by most patients, even those with extensive previous treatments.

For M7824, studies have demonstrated that it works well and is generally safe for patients with advanced cancer when used alone. Trials found no major safety issues.

Overall, past studies have shown both the HPV vaccine and M7824 to be safe. However, joining a new trial always involves some risk. Discuss any concerns with the trial team.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for HPV-associated cancers because they combine innovative approaches to tackle the disease. Unlike traditional treatments like chemotherapy and radiation, the investigational treatments use a Human Papillomavirus (HPV) vaccine, PRGN-2009, designed to train the immune system to recognize and attack HPV-related cancer cells. Additionally, M7824 is a unique bifunctional fusion protein that targets both the PD-L1 and TGF-β pathways, which are often used by cancer cells to evade the immune system. This dual-action approach could potentially improve the immune response against cancer cells, offering a novel strategy compared to existing therapies.

What evidence suggests that the HPV vaccine combined with M7824 could be effective for HPV-associated cancers?

Research has shown that the HPV vaccine, PRGN-2009, combined with a checkpoint inhibitor, helped about 30% of patients with heavily treated HPV-related cancers achieve significant tumor reduction. Nearly one-third of these patients experienced noticeable tumor shrinkage. In this trial, some participants will receive the HPV vaccine alone, while others will receive it with M7824. Other studies have found that M7824 alone can lead to a 35-40% reduction in tumors for patients with advanced HPV-related cancers. This suggests that both treatments are promising individually. Combining PRGN-2009 with M7824 might enhance these results by boosting the body's immune response.12345

Who Is on the Research Team?

CF

Charalampos Floudas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

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.
See 20 more

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.
See 14 more

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
4Treatment groups
Experimental Treatment
Group I: 4/Arm 2BExperimental Treatment2 Interventions
Group II: 3/Arm 2AExperimental Treatment2 Interventions
Group III: 2/Arm 1BExperimental Treatment2 Interventions
Group IV: 1/Arm 1AExperimental Treatment1 Intervention

Find a Clinic Near You

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

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

Citations

Press ReleasesPRGN-2009 combined with an investigational checkpoint inhibitor resulted in a 30% ORR in patients with heavily pre-treated HPV-associated cancers.
Precigen Announces Positive Phase 1 Data for Off-the- ...PRGN-2009 combined with an investigational checkpoint inhibitor resulted in a 30% ORR in patients with heavily pre-treated HPV-associated cancers.
PRGN-2009 and bintrafusp alfa for patients with advanced or ...Monotherapy with ICBs has shown activity against HPV-associated cancers including OPC [7–9], cervical, [10, 11] and anal [12–14] cancers; ...
Press ReleasesPrecigen's AdenoVerse immunotherapy platform is currently under clinical investigation in a Phase 1/2 study of PRGN-2009 AdenoVerse ...
Phase II Trial of Immunotherapeutic HPV Vaccine PRGN ...(i) PRGN-2009 AdenoVerse Gene Therapy in HPV-associated cancers: PRGN-2009 Phase 2 clinical trials under a cooperative research and development agreement ...
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