HPV Vaccine + Pembrolizumab for Oropharyngeal Cancer

Overseen By Charalampos Floudas, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Glucocorticoids, Immunosuppressors

Disqualifiers: Pregnancy, Autoimmune disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 7

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments: pembrolizumab (also known as KEYTRUDA or MK-3475, an immunotherapy drug) and an HPV vaccine. The aim is to determine if they work better together against HPV-positive cancers in and around the mouth. Researchers hope this approach might improve outcomes for patients with these cancers. The trial seeks adults newly diagnosed with HPV-positive cancers in these areas who are scheduled for surgery or chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to potentially groundbreaking cancer treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic glucocorticoids or other immunosuppressive drugs, you must stop them at least 1 week before joining the study. You can continue adjuvant hormonal therapy if you have a definitively treated cancer.

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

Research shows that both pembrolizumab and the HPV vaccine PRGN-2009 are generally safe. Pembrolizumab treats various cancers and has been tested in individuals with HPV-related cancers. It is usually well-tolerated, though some may experience side effects like tiredness or skin reactions.

PRGN-2009 remains under study. In one study, about 30% of patients responded well, even after many previous treatments. While the study primarily assessed efficacy, the safety results suggest it can be used without major issues.

Combining these treatments aims to improve outcomes for HPV-positive mouth cancers. The current study phase indicates acceptable safety so far, but more information is needed to fully understand any risks. Participants should discuss possible side effects with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for oropharyngeal cancer?

Unlike the standard treatments for oropharyngeal cancer, which typically involve surgery, radiation, and chemotherapy, the combination of the HPV vaccine PRGN-2009 and pembrolizumab is unique because it leverages the immune system to fight cancer. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells. PRGN-2009, on the other hand, is a therapeutic vaccine designed to specifically target HPV-related cancer cells, potentially enhancing the body's immune response. Researchers are excited about this approach because it could offer a more targeted treatment with fewer side effects compared to traditional therapies, and it harnesses the power of the immune system in a novel way.

What evidence suggests that this trial's treatments could be effective for HPV-positive oropharyngeal cancer?

Research has shown that both the HPV vaccine PRGN-2009 and the drug pembrolizumab offer promise for treating HPV-related cancers. In this trial, participants will receive a combination of PRGN-2009 and pembrolizumab as induction/neoadjuvant therapy. One study found that combining PRGN-2009 with a checkpoint inhibitor led to a positive response in 30% of patients with heavily treated HPV-related cancers. Pembrolizumab alone has also improved outcomes for individuals with HPV-positive head and neck cancers. This trial aims to determine if combining these treatments can enhance their effectiveness for people with these types of cancers. ^{2 3 4 6 7}

Who Is on the Research Team?

Charalampos Floudas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed HPV-positive oropharyngeal cancer, who are planning standard treatment and can sign consent. They must be willing to undergo biopsies, have measurable disease, and meet certain health criteria including HIV, Hepatitis B/C status. Women must agree to use contraception.

Inclusion Criteria

Subjects must have measurable disease, per RECIST 1.1

Ability to understand and willingness to sign a written informed consent document

Adequate hematologic function at screening: ANC >=1 x 10^9/L, Hgb >= 9 g/dL, Platelets >= 75,000/microliter

Exclusion Criteria

I have had a transplant of tissue or an organ from another person.

Pregnant individuals

I am currently taking certain steroids or drugs that suppress my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction/Neoadjuvant Therapy

Participants receive PRGN-2009 and pembrolizumab before definitive treatment

4-5 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Follow-up contacts by phone at 3 and 6 months, then annually

Long-term Follow-up

Assess overall survival and recurrence-free survival once a year for 5 years

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• PRGN-2009

Trial Overview The trial is testing the combination of an immunotherapeutic HPV vaccine (PRGN-2009) with Pembrolizumab before standard cancer treatments in patients with HPV-associated mouth cancers. It involves injections and infusions followed by multiple clinic visits for monitoring.

How Is the Trial Designed?

Group I: Arm 1 Experimental Treatment 2 Interventions

PRGN 5x10\^11 Viral Particles (VP) SC plus pembrolizumab 200mg IV as induction/ neoadjuvant therapy

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

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

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In a study of 36 patients with resectable HPV-unrelated head and neck squamous-cell carcinoma, neoadjuvant pembrolizumab was found to be safe, with no serious adverse events reported during treatment.

The treatment resulted in a pathologic tumor response in 44% of patients, and the one-year relapse rate for those with high-risk pathology was significantly lower at 16.7%, compared to the historical rate of 35%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus-Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial. Uppaluri, R., Campbell, KM., Egloff, AM., et al.[2021]

Pembrolizumab has been approved by the FDA as the first-line treatment for both HPV-positive and HPV-negative recurrent head and neck squamous cell carcinoma, marking it as a significant advancement in immunotherapy for this cancer type.

The approval allows pembrolizumab to be used either alone for tumors expressing PD-L1 or in combination with chemotherapy, highlighting the need for healthcare providers to be aware of and manage potential immune-related toxicities such as dermatitis and mucositis associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. Fazer, C., Price, KA.[2021]

The Phase III trial KEYNOTE-412 is designed to evaluate the efficacy and safety of pembrolizumab, an immune checkpoint inhibitor, when used alongside chemoradiation therapy (CRT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).

Previous Phase Ib studies have indicated that combining pembrolizumab with CRT is safe and feasible, supporting its potential use in this larger trial to improve treatment outcomes for patients with locally advanced HNSCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Machiels, JP., Tao, Y., Burtness, B., et al.[2021]

Pembrolizumab (KEYTRUDA) received accelerated FDA approval for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) based on a study of 174 patients, showing an objective response rate of 16% and a duration of response ranging from 2.4 to 27.7 months.

The safety profile included serious adverse reactions such as pneumonia and respiratory failure, but the overall benefit-risk assessment was deemed acceptable, marking pembrolizumab as the first new treatment option for HNSCC since 2006.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. Larkins, E., Blumenthal, GM., Yuan, W., et al.[2019]

In a study of 257 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) treated with pembrolizumab, biomarkers such as tumor mutational burden (TMB), PD-L1 expression, and T-cell-inflamed gene expression profile (Tcellinf GEP) were found to be significantly associated with overall response rates (ORR) to the treatment.

The study indicated that higher levels of these biomarkers correlated with better treatment responses, suggesting that they could be useful in predicting how well patients will respond to pembrolizumab therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers predictive of response to pembrolizumab in head and neck cancer. Pfister, DG., Haddad, RI., Worden, FP., et al.[2023]

In a phase IB study involving 59 patients with locally advanced head and neck squamous cell carcinoma, the combination of pembrolizumab with cisplatin-based chemoradiotherapy was found to be safe, with a high completion rate of treatment and only 8.8% of patients experiencing immune-related adverse events.

The treatment showed promising efficacy, with complete response rates of 85.3% for HPV-positive and 78.3% for HPV-negative patients, suggesting that this combination warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Pembrolizumab With Chemoradiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Phase IB Study. Powell, SF., Gold, KA., Gitau, MM., et al.[2022]

Citations

1. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-announces-positive-phase-1-data-shelf-prgn-2009

Press Releases PRGN-2009 combined with an investigational checkpoint inhibitor resulted in a 30% ORR in patients with heavily pre-treated HPV-associated cancers.

2. prnewswire.com prnewswire.com/news-releases/precigen-announces-positive-phase-1-data-for-off-the-shelf-prgn-2009-adenoverse-immunotherapy-alone-and-in-combination-with-an-investigational-checkpoint-inhibitor-in-patients-with-recurrentmetastatic-hpv-associated-cancers-301841791.html

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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11928712/

PRGN-2009 and bintrafusp alfa for patients with advanced or ... This first-in-human phase 1 study (NCT04432597) evaluated the safety and recommended phase 2 dose (RP2D) of PRGN-2009, a gorilla adenoviral- ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT05996523

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 (CRADA) ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06639

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN ... Two treatments (the drug pembrolizumab and the HPV vaccine PRGN-2009) have been shown to work well when used individually against these cancers. Researchers ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS6124

Phase II trial of immunotherapeutic HPV vaccine PRGN- ... This is a single-site, single-arm, Phase II clinical trial investigating the biological activity of neoadjuvant PRGN-2009 and Pembrolizumab in early-stage HPV- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05996523

NCT05996523 | Phase II Trial of Immunotherapeutic HPV ... Cancers in and around the mouth associated with human papilloma virus (HPV) are common. Two treatments (the drug pembrolizumab and the HPV vaccine PRGN-2009) ...