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

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a combination of a cancer vaccine, an immune-boosting drug, and standard treatments in adults with a specific type of head and neck cancer linked to HPV. The goal is to see if this combination improves patient survival.

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.

What data supports the effectiveness of the drug combination of HPV Vaccine, Pembrolizumab, and Cisplatin for head and neck cancer?

Research shows that pembrolizumab, when combined with chemoradiotherapy (a mix of chemotherapy and radiation), is safe and feasible for treating locally advanced head and neck cancer. Pembrolizumab has also shown antitumor activity in recurrent or metastatic head and neck cancer, suggesting potential benefits when used with other treatments like cisplatin. ^{1 2 3 4 5}

Is the combination of HPV Vaccine, Pembrolizumab, and Cisplatin safe for treating head and neck cancer?

Pembrolizumab has been evaluated for safety in patients with head and neck cancer, showing some serious side effects like pneumonia, breathing difficulties, confusion, vomiting, and immune-related issues like lung inflammation and liver problems. Cisplatin is a standard treatment for head and neck cancer, but some patients cannot tolerate it due to its side effects. The combination of these treatments is being studied to see if it is safe and effective. ^{2 4 5 6 7}

What makes the HPV Vaccine + Pembrolizumab + Cisplatin treatment unique for head and neck cancer?

This treatment is unique because it combines an HPV vaccine with pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells, and cisplatin, a chemotherapy drug, along with advanced radiotherapy. This combination aims to enhance the immune response against the cancer and improve treatment outcomes compared to standard therapies. ^{1 2 3 4 7}

Research Team

Dan P. Zandberg

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2022]

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

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]

3. England 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. [2021]

4. Switzerland 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. [2023]

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

Pembrolizumab and its use in the treatment of recurrent or metastatic head and neck cancer. [2019]

6. England 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. [2019]

7. United States 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. [2021]