Immunotherapy + Radiation for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Loren Mell, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Loren Mell, MD

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Prior malignancy, Metastases, Autoimmune, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on medications for an active autoimmune disease or an active infection, you may need to discuss this with the trial team, as these conditions are part of the exclusion criteria.

What data supports the effectiveness of the treatment combining immunotherapy and radiation for head and neck cancer?

Research shows that combining pembrolizumab, an immune therapy drug, with radiation can be effective for head and neck cancer, especially when cisplatin, a common chemotherapy drug, cannot be used. Pembrolizumab has been approved for use in cases where the cancer has returned or spread after other treatments, and studies suggest it works well with radiation to stimulate the immune system against the tumor. ^{1 2 3 4 5}

Is the combination of immunotherapy and radiation safe for head and neck cancer patients?

The combination of pembrolizumab (an immunotherapy drug) and radiation therapy has been studied for safety in patients with head and neck cancer. Common serious side effects include pneumonia, breathing difficulties, confusion, vomiting, and immune-related issues like lung inflammation and liver problems. However, the overall safety profile is considered acceptable for this patient group. ^{1 2 6 7 8}

What makes the Immunotherapy + Radiation treatment for head and neck cancer unique?

This treatment combines pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with radiation therapy, which can enhance the immune response against tumors. This combination is particularly beneficial for patients who cannot use cisplatin, a common chemotherapy drug, making it a novel approach for treating locally advanced head and neck cancer. ^{1 3 9 10 11}

Research Team

Loren Mell, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for adults with certain high-risk head and neck cancers, including oropharynx, larynx, nasopharynx, and oral cavity squamous cell carcinoma. Participants must have no distant metastases, be HIV negative, not pregnant or breastfeeding, agree to use contraception during the study period and have adequate organ function.

Inclusion Criteria

My condition is considered high-intermediate risk.

Measurable disease based on RECIST 1.1

My blood tests within the last month show normal results.

Exclusion Criteria

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial

I have been diagnosed with HIV.

I have an active Hepatitis B or C infection.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intensity-modulated radiation therapy with either concurrent cisplatin or pembrolizumab

6.5 weeks

Weekly visits for radiation therapy

Adjuvant Therapy

Participants in the pembrolizumab arm receive additional cycles of pembrolizumab

Up to 60 weeks

Every 3 weeks for pembrolizumab infusion

Follow-up

Participants are monitored for progression-free survival and other outcomes

3 years

Treatment Details

Interventions

• Cisplatin (Alkylating agents)
• Pembrolizumab (Monoclonal Antibodies)
• Radiation therapy (Radiation)

Trial Overview The trial compares pembrolizumab (an experimental immunotherapy drug) plus radiation therapy against the standard treatment of cisplatin chemotherapy plus radiation therapy in treating head and neck squamous cell carcinoma.

Participant Groups

Group I: Experimental-Radiotherapy/pembrolizumab Experimental Treatment 2 Interventions

Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent and adjuvant pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles

Group II: Control-radiotherapy/cisplatin Active Control 2 Interventions

Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent cisplatin 100 mg/m2 every 3 weeks for 3 cycles (7 weeks)

Cisplatin is already approved in Canada, Japan for the following indications:

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?

Loren Mell, MD

Lead Sponsor

Trials

2

Recruited

160+

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

Findings from Research

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]

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]

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 study of 4520 patients with stage III to IVb head and neck squamous cell carcinoma, those treated with cisplatin alongside radiation therapy had significantly better overall survival compared to those treated with cetuximab, with a median survival of 4.1 years versus 1.7 years for cetuximab.

After adjusting for treatment biases, cetuximab continued to show inferior overall survival rates, suggesting that cisplatin is a more effective partner for radiation therapy in the nonoperative management of this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab with definitive concurrent radiotherapy for head and neck squamous cell carcinoma: An analysis of Veterans Health Affairs data. Bauml, JM., Vinnakota, R., Anna Park, YH., et al.[2023]

Immune checkpoint inhibitors, like nivolumab and pembrolizumab, have become the standard treatment for recurrent or metastatic head and neck squamous cell carcinoma that cannot be treated with surgery or radiotherapy.

Nivolumab is approved for use regardless of PD-L1 expression in patients who have progressed after platinum therapy, while pembrolizumab requires specific conditions related to PD-L1 expression and prior treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

["Immunotherapy in head and neck squamous cell carcinoma"]. Marret, G., Borcoman, É., Le Tourneau, C.[2021]

References

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

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

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

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

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. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]

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

Cisplatin versus cetuximab with definitive concurrent radiotherapy for head and neck squamous cell carcinoma: An analysis of Veterans Health Affairs data. [2023]

6. Greece pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. [2023]

7. 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]

8. Greece pubmed.ncbi.nlm.nih.gov

Safety and preliminary activity of pembrolizumab-carboplatin-paclitaxel in heavily pretreated and/or fragile patients with PDL1-positive recurrent/metastatic head and neck cancer. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Cisplatin versus cetuximab given concurrently with definitive radiation therapy for locally advanced head and neck squamous cell carcinoma. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. [2023]

11. France pubmed.ncbi.nlm.nih.gov

["Immunotherapy in head and neck squamous cell carcinoma"]. [2021]