Pembrolizumab + Chemotherapy for Head and Neck Cancer

Overseen By Ari Rosenberg, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Active infection, Brain metastases, Autoimmune disorders, 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: 2

Duration: 6 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a blood test measuring tumor DNA can guide the optimal use of chemotherapy and immunotherapy for people with head and neck cancer. Researchers seek to discover whether adding occasional chemotherapy to regular immunotherapy is more effective than using immunotherapy alone. The study seeks participants with head and neck cancer that has recurred or spread and who have not yet received certain treatments for their condition. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

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.

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

Research has shown that pembrolizumab, a medication used in this study, is generally well-tolerated. In studies involving 192 patients with head and neck squamous cell carcinoma (HNSCC), most patients tolerated pembrolizumab well. However, like many treatments, it can cause side effects, which vary among individuals.

When combined with carboplatin and paclitaxel, research indicates that this combination is generally safe. While side effects can occur, they are usually not severe enough to outweigh the potential benefits. Many patients have continued treatment without major issues.

Overall, safety data suggest that both pembrolizumab alone and in combination with carboplatin and paclitaxel are generally well-tolerated, with most side effects being manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pembrolizumab in combination with chemotherapy for head and neck cancer because this approach leverages the power of immunotherapy alongside traditional chemotherapy. Pembrolizumab is an immune checkpoint inhibitor that helps the immune system recognize and attack cancer cells more effectively, which is different from standard chemotherapy treatments that directly target and kill rapidly dividing cells. This combination has the potential to enhance the effectiveness of treatment by not only attacking the cancer cells directly but also empowering the body's own immune system to fight back. Meanwhile, using pembrolizumab alone offers a treatment option that may reduce the need for traditional chemotherapy, potentially leading to fewer side effects while still harnessing the immune system's strength. These innovative approaches open up new possibilities for improved outcomes in patients with head and neck cancer.

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

Research shows that pembrolizumab, when used alone, can benefit people with head and neck squamous cell carcinoma (HNSCC). Studies have found that pembrolizumab can extend survival compared to standard treatments. In this trial, some participants will receive pembrolizumab alone, while others will receive it combined with chemotherapy drugs like carboplatin and paclitaxel. This combination has shown promising results in fighting tumors and is often used as the first treatment for patients with recurrent or metastatic head and neck cancer. Overall, evidence suggests that pembrolizumab, both alone and with chemotherapy, can effectively treat head and neck cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Ari Rosenberg, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

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+

Published Research Related to This Trial

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 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]

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]

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 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 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]

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 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]

Citations

1. merck.com merck.com/news/european-commission-approves-keytruda-pembrolizumab-as-part-of-a-treatment-regimen-for-adults-with-resectable-locally-advanced-head-and-neck-squamous-cell-carcinoma-la-hnscc-expressing-pd-l1/

European Commission Approves KEYTRUDA® ... KEYTRUDA is indicated for the treatment of adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694497/

Real-World Evidence on the Effectiveness of Pembrolizumab ... The study showed some beneficial effects of pembrolizumab monotherapy in recurrent/metastatic/unresectable HNSCC patients in real-world scenarios.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042

Study Details | NCT02252042 | Pembrolizumab (MK-3475) ... The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2415434

Neoadjuvant and Adjuvant Pembrolizumab in Locally ... The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced ...

5. keytruda.com keytruda.com/head-and-neck-cancer/clinical-trial-results-with-chemotherapy/

KEYTRUDA used with chemotherapy as first treatment Half of the people who received KEYTRUDA and chemotherapy were alive without their cancer spreading, growing, or getting worse at 4.9 months, compared to 5.1 ...

6. fda.gov fda.gov/drugs/resources-information-approved-drugs/pembrolizumab-keytruda

pembrolizumab (KEYTRUDA) Safety data was evaluated in 192 patients with HNSCC receiving at least one dose of pembrolizumab 10 mg/kg every 2 weeks or 200 mg every 3 weeks ...

7. keytruda.com keytruda.com/head-and-neck-cancer/

head and neck squamous cell cancer (HNSCC) Important Safety Information. KEYTRUDA is a medicine that may treat certain cancers by working with your immune system. KEYTRUDA can cause your immune system ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6048158/

Efficacy and safety of pembrolizumab in recurrent/metastatic ... These data demonstrate that a subset of patients will receive long-term benefit from treatment with pembrolizumab, a paradigm rarely observed ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042

Study Details | NCT02252042 | Pembrolizumab (MK-3475) ... The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard treatment. Official Title. A Phase III ...