HPV Vaccine + Pembrolizumab + Cisplatin for Head and Neck Cancer

Overseen By Rosemarie Angelo, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dan Zandberg

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: AIDS, Hepatitis B/C, Autoimmune, 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

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments, including a vaccine, pembrolizumab (an immunotherapy drug), and cisplatin (a chemotherapy drug), for HPV-associated head and neck cancer. Researchers aim to determine if this combination effectively treats cancers in the throat area, specifically for those with an intermediate risk. Ideal participants are newly diagnosed with HPV-related head and neck cancer and have not previously received chemotherapy or radiation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 medications for active infections, autoimmune diseases, or have recently used certain investigational drugs, you may need to discuss this with the trial team.

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

Research shows that the combination of treatments in this trial has been tested for safety in people. Pembrolizumab, cisplatin, and IMRT (a precise type of radiation therapy) are already common treatments for head and neck cancer. These treatments are generally well-tolerated, with known side effects such as nausea, tiredness, and lower blood cell counts.

ISA101b is a newer vaccine targeting HPV-related cells. Studies have found it can cause mild side effects, such as pain at the injection site and flu-like symptoms. When combined with pembrolizumab and cisplatin, ISA101b has not shown any unexpected safety problems. This suggests that the treatment plan is reasonably safe, though some side effects are expected. Always consider the potential benefits and risks, and discuss them with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

The combination of HPV vaccine (ISA101b), pembrolizumab, and cisplatin for head and neck cancer is unique because it integrates a multi-pronged approach to tackle the disease. Unlike the standard treatments, which typically involve surgery, radiation, and chemotherapy, this regimen introduces an innovative use of an HPV vaccine (ISA101b) to boost the immune response against cancer cells. Pembrolizumab, an immunotherapy drug, further enhances this effect by inhibiting a protein that prevents the immune system from attacking cancer cells. Cisplatin remains a powerful chemotherapy agent, adding a traditional cancer-fighting backbone to the mix. Researchers are excited because this combination could potentially lead to better outcomes by targeting the cancer through both immune activation and direct cytotoxic effects.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

Research has shown that the combination of treatments in this trial could be promising for treating head and neck cancer. Participants will receive a combination of Pembrolizumab, Cisplatin, IMRT, and the HPV vaccine ISA101b. Pembrolizumab has been proven to extend the lives of patients with head and neck cancer. Cisplatin, when combined with radiation, effectively treats these types of cancers and is commonly used. The HPV vaccine, ISA101b, has been linked to a reduced risk of developing head and neck cancers, particularly those related to HPV infections. Together, these treatments might offer a comprehensive approach by targeting the cancer in several ways. ^{6 7 8 9 10}

Who Is on the Research Team?

Dan P. Zandberg

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, intermediate risk HPV-16-associated head and neck squamous cell carcinoma without distant metastasis. Eligible patients must have a specific type of tumor in the oropharynx or unknown primary site, meet certain disease stage criteria, not have had prior treatments for head and neck cancer, be free from other cancers for at least 2 years (with some exceptions), and show adequate organ function.

Inclusion Criteria

My organs are functioning well.

My condition is considered to be at an intermediate risk level.

Written informed consent must be obtained from all patients prior to study registration.

Exclusion Criteria

Current participation in or previous participation in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment.

I haven't had monoclonal antibody treatment in the last 4 weeks or have recovered from its side effects.

I have been treated with specific immune system targeting drugs before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive the ISA101b vaccine targeting HPV, starting 2 weeks prior to cisplatin-IMRT and 1 week prior to pembrolizumab

5 weeks

3 visits (in-person)

Chemoradiotherapy

Participants receive cisplatin-IMRT and pembrolizumab concurrently

7 weeks

Weekly visits (in-person)

Maintenance Treatment

Participants continue pembrolizumab for a 15-week maintenance period after completion of cisplatin-IMRT

15 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• IMRT (Intensity Modulated Radiotherapy)
• ISA101b
• Pembrolizumab

Trial Overview The study tests a new treatment combo: pembrolizumab (an immune therapy), ISA101b (HPV-16 vaccine), cisplatin (chemotherapy), and IMRT (targeted radiotherapy). It's designed to see if this mix can better treat local-regionally advanced head and neck cancer linked to HPV-16 compared to current standards.

How Is the Trial Designed?

Group I: IMRT + Pembrolizumab + Cisplatin + ISA101b Experimental Treatment 4 Interventions

IMRT (Intensity Modulated Radiotherapy) of 70 Gy in 35 fractions over 7 weeks (5 fractions per week). Pembrolizumab will be administered at 200 mg (fixed dose) IV every 3 weeks (+/- 3 days), beginning beginning one week (week -1) prior to concurrent cisplatin-IMRT. Cisplatin will be administered at 100 mg/m2 IV on days 1(Week 0) and 22 (Week 3). ISA101b will be administered as three rounds of vaccination 3-4 weeks apart via two SC injections per vaccination round at 100ug/peptide, before pembrolizumab treatment. Vaccination #1 will be administered 1 week before pembrolizumab.

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Dan Zandberg

Lead Sponsor

Trials

7

Recruited

330+

Robert Ferris

Lead Sponsor

Trials

7

Recruited

240+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

ISA Pharmaceuticals

Industry Sponsor

Trials

5

Recruited

400+

Published Research Related to This Trial

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]

Pembrolizumab, an immune checkpoint inhibitor, has been approved by the FDA for treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), offering a new option with potentially improved efficacy compared to traditional chemotherapy and EGFR inhibitors.

This review discusses the pharmacology and tolerability of pembrolizumab, emphasizing its mechanism of action by blocking the PD-1 receptor, which may enhance the immune response against HNSCC tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. Sheth, S., Weiss, J.[2019]

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]

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]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., 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]

The ADRISK trial is investigating whether adding pembrolizumab to standard adjuvant radio(chemo)therapy (aRCT) improves event-free survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who are at intermediate to high risk after surgery.

This phase II multicenter trial will involve 240 patients and aims to compare the effectiveness of aRCT alone versus aRCT combined with pembrolizumab, with endpoints focused on event-free and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial. Wiegand, S., Wichmann, G., Vogt, J., et al.[2023]

Citations

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Cisplatin-Based Chemotherapy Options for Recurrent and/ ... When studying its efficacy in the treatment of 31 patients with R/M HNSCC, OS was found to be 4.5 months with a RR of 25.8%. This response was comparable to ...

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Study Details | NCT04369937 | HPV-16 Vaccination and ... This study aims to enroll adult male and female patients who have intermediate risk disease with histologically-confirmed head and neck squamous cell carcinoma ...

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