Pembrolizumab + Chemotherapy for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Ari Rosenberg, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Chicago

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Active infection, Brain metastases, Autoimmune disorders, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

By doing this study, the research team would like to learn if using a blood test that measures the amount of tumor DNA in blood can help guide how to use chemotherapy combined with immunotherapy for individuals with head and neck cancer. Using this blood test, the research team hopes to learn if intermittent (occasional) chemotherapy added to immunotherapy will work better than immunotherapy alone. Participation in this research will last about two years.

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 investigational agents or certain immunosuppressive therapies, you may not be eligible to participate.

What data supports the effectiveness of the drug Pembrolizumab in combination with chemotherapy for head and neck cancer?

Research shows that Pembrolizumab, when used alone or with chemotherapy, is effective in treating head and neck squamous cell carcinoma, especially in cases where the cancer has returned or spread after initial treatment. It works by blocking a pathway that cancer cells use to hide from the immune system, helping the body to fight the cancer more effectively. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, Carboplatin, and Paclitaxel safe for treating head and neck cancer?

The combination of Pembrolizumab, Carboplatin, and Paclitaxel has been generally well tolerated in patients with head and neck cancer, though some serious side effects like anemia, neutropenia (low white blood cell count), and hypertension (high blood pressure) have been reported. Common side effects include diarrhea, hypothyroidism (underactive thyroid), and skin rash, with rare cases of severe lung inflammation (pneumonitis). ^{1 6 7 8 9}

What makes the drug pembrolizumab combined with chemotherapy unique for head and neck cancer?

Pembrolizumab, when combined with chemotherapy, offers a novel approach for treating head and neck cancer by blocking the PD-1 pathway, which helps the immune system attack cancer cells more effectively. This combination is particularly beneficial for patients with recurrent or metastatic cancer, where traditional treatments have limited success and high toxicity. ^{1 3 4 10 11}

Research Team

Ari Rosenberg, MD

Principal Investigator

University of Chicago

Eligibility Criteria

Adults with confirmed recurrent or metastatic head and neck cancer, who haven't had systemic therapy for this setting, can join. They must have a performance status of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but can do light work), measurable disease, normal organ/marrow function, and provide tissue for PD-L1 analysis. Women must not be pregnant/breastfeeding and agree to contraception; men with partners capable of pregnancy must also use contraception.

Inclusion Criteria

My organ and bone marrow functions are normal.

I am fully active or restricted in physically strenuous activity but can do light work.

Have measurable disease based on RECIST 1.1 criteria

Exclusion Criteria

I have received an organ or tissue transplant from another person.

I have cancer that has spread to my brain.

I had radiation therapy less than 2 weeks ago or am still dealing with its side effects.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab with or without chemotherapy based on circulating tumor DNA response for two 21-day cycles

6 weeks

2 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Extension

Participants may continue to receive treatment based on response and safety assessments

Long-term

Treatment Details

Interventions

• Carboplatin (Alkylating agents)
• Paclitaxel (Anti-metabolites)
• Pembrolizumab (Monoclonal Antibodies)

Trial Overview The trial is testing Pembrolizumab combined with chemotherapy drugs Carboplatin and Paclitaxel in patients with head and neck cancer. It aims to see if using a blood test to measure tumor DNA helps guide the intermittent addition of chemotherapy to immunotherapy compared to just immunotherapy alone over about two years.

Participant Groups

Group I: Group 2: Participants Who Receive Pembrolizumab + Chemotherapy with Carboplatin and Paclitaxel Experimental Treatment 3 Interventions

Participants in this group will receive 200 mg of pembrolizumab through an intravenous (IV) needle inserted into the arm plus chemotherapy with carboplatin (AUC 6) on day 1 and paclitaxel (200 mg) on day 1 of each 21-day cycle for two cycles.

Group II: Group 1: Participants Who Receive Pembrolizumab (Alone) Experimental Treatment 1 Intervention

Participants in this group will receive pembrolizumab 200 mg through an intravenous (IV) needle inserted into the arm. Medications will be given on day 1 of each 21-day cycle for two cycles..

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Pete Salzmann

University of Chicago

Chief Executive Officer since 2018

MD from University of Chicago’s Pritzker School of Medicine, MBA from Stanford University’s Graduate School of Business

Anh Nguyen

University of Chicago

Chief Medical Officer

MD from Rutgers New Jersey Medical School, MBA from University of Chicago

Findings from Research

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 study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

In a study involving 882 participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), pembrolizumab alone significantly improved overall survival compared to cetuximab with chemotherapy, especially in patients with high PD-L1 expression (CPS of 20 or more).

Pembrolizumab combined with chemotherapy also showed improved overall survival compared to cetuximab with chemotherapy across all populations, indicating that pembrolizumab is an effective first-line treatment option for HNSCC, particularly for those with PD-L1 positivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Burtness, B., Harrington, KJ., Greil, R., et al.[2021]

In a study of 38 patients with p16+ oropharyngeal squamous cell carcinoma, there was a 76% agreement in PD-L1 combined positive scores (CPS) between primary tumors and lymph node metastases, indicating variability in scoring between these specimens.

The interobserver agreement for CPS scoring was fair to substantial, suggesting that additional evaluations may be necessary to ensure accurate scoring, especially for patients who might benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. Kaur, A., Kuchta, K., Watkin, W., 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]

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 small retrospective study of 10 patients with recurrent or metastatic squamous cell carcinoma of the head and neck, the combination of pembrolizumab with carboplatin and paclitaxel (pembro + CP) was well tolerated, with 100% of patients experiencing mild adverse events and 30% experiencing more severe side effects.

The overall response rate (ORR) was 14% with one complete response, and the disease control rate (DCR) was 43%, indicating that while the treatment showed some effectiveness, further prospective studies are needed to fully evaluate its safety and efficacy.

NCBI (Pubmed)

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. Cabezas-Camarero, S., Merino-Menéndez, S., Cabrera-Martín, MN., et al.[2023]

In a study of 167 patients with recurrent/metastatic squamous cell carcinoma of the head and neck treated with pembrolizumab, the median overall survival was 22.7 months and progression-free survival was 5.1 months for those receiving pembrolizumab alone, indicating significant efficacy.

The presence of immune-related adverse events (irAEs) was associated with better progression-free survival, suggesting that these side effects may serve as important prognostic factors in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Pembrolizumab in Recurrent/Metastatic Squamous Cell Head and Neck Carcinoma: A Multicenter Retrospective Study. Okada, T., Fushimi, C., Matsuki, T., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[2022]

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 study with 882 patients over a median follow-up of 45 months, pembrolizumab and pembrolizumab-chemotherapy showed significant improvements in overall survival compared to cetuximab-chemotherapy for recurrent/metastatic head and neck squamous cell carcinoma, particularly in patients with high PD-L1 expression (CPS ≥ 20).

The analysis also indicated that patients who received pembrolizumab-based therapies had favorable outcomes in subsequent treatments, with improved progression-free survival on next-line therapies, highlighting the long-term efficacy of pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. Harrington, KJ., Burtness, B., Greil, R., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Greece pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. [2021]

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

Programmed Death Ligand-1 Combined Positive Score Concordance and Interrater Reliability in Primary Tumors and Synchronous Lymph Node Metastases in Resected Cases of p16+ Oropharyngeal Squamous Cell Carcinoma. [2023]

5. 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]

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. 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]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

10. 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]

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

Pembrolizumab With or Without Chemotherapy in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Updated Results of the Phase III KEYNOTE-048 Study. [2023]