Pembrolizumab + Epacadostat for Head and Neck Cancer

Recruiting at 72 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Disqualifiers: Nasopharynx carcinoma, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Minimum 9 weeks

89 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions the use of protocol-defined prior/concomitant therapy, which might mean some medications could be restricted. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug combination Pembrolizumab + Epacadostat for head and neck cancer?

Research shows that Pembrolizumab, a drug that helps the immune system fight cancer, is approved for use in head and neck cancer after other treatments have failed. Additionally, combinations of drugs like cisplatin or carboplatin with 5-fluorouracil and cetuximab have been shown to be effective in treating head and neck cancer, suggesting that similar combinations may also be beneficial. ^{1 2 3 4 5}

Is the combination of pembrolizumab and epacadostat safe for head and neck cancer patients?

The combination of pembrolizumab with other drugs like carboplatin and paclitaxel has been generally well tolerated in patients with head and neck cancer, though some experienced mild to moderate side effects like anemia (low red blood cell count) and hypertension (high blood pressure). Safety data specifically for pembrolizumab and epacadostat together is limited, but pembrolizumab alone has been approved for use in similar conditions, indicating a level of safety in humans. ^{1 3 5 6 7}

What makes the drug combination of Pembrolizumab and Epacadostat unique for head and neck cancer?

This drug combination is unique because it combines Pembrolizumab, an immune checkpoint inhibitor that blocks PD-1 to help the immune system attack cancer cells, with Epacadostat, an IDO inhibitor that may enhance immune response by reducing immune suppression. This approach is novel compared to traditional chemotherapy, which often has more side effects and less targeted action. ^{1 3 8 9 10}

What is the purpose of this trial?

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab + cisplatin or carboplatin + 5-fluorouracil) as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Research Team

Mark Jones, MD

Principal Investigator

Incyte Corporation

Eligibility Criteria

This trial is for adults with recurrent or metastatic head and neck squamous cell carcinoma who have measurable disease, are in good physical condition (ECOG 0-1), have proper organ function, and can provide a tumor specimen. It's not for those with recent other cancers, active autoimmune diseases treated within the last 2 years, HIV or hepatitis B/C infections, CNS metastases, or certain types of head and neck cancer.

Inclusion Criteria

My organs are functioning well according to the test results.

Measurable disease based on RECIST v1.1

My oropharyngeal cancer has been tested for HPV.

Exclusion Criteria

I have been treated for an autoimmune disease in the last 2 years.

Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority

My cancer originates from the nasopharynx, salivary gland, or is of an unknown primary origin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab plus epacadostat, pembrolizumab monotherapy, or the EXTREME regimen as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma

Minimum 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 14 months

Treatment Details

Interventions

• 5-Fluorouracil
• Carboplatin
• Cetuximab
• Cisplatin
• Epacadostat
• Pembrolizumab

Trial Overview The study compares three treatments: pembrolizumab plus epacadostat; pembrolizumab alone; and the EXTREME regimen (cetuximab with cisplatin/carboplatin plus 5-fluorouracil). The goal is to see which treatment works best as a first-line therapy for this type of cancer.

Participant Groups

Group I: Pembrolizumab + Epacadostat Experimental Treatment 2 Interventions

Group II: Pembrolizumab Experimental Treatment 1 Intervention

Group III: EXTREME Active Control 4 Interventions

EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.

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

Approved in European Union as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer
• Ovarian cancer

Approved in United States as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Approved in Canada as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer

Approved in Japan as 5-FU for:

• Colorectal cancer
• Breast cancer
• Stomach cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

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 study of adult patients with metastatic head and neck squamous cell cancer, substituting 5-fluorouracil (5-FU) with a taxane in a pembrolizumab-based treatment regimen did not increase toxicity or worsen survival outcomes.

Patients receiving the taxane combination experienced significantly lower rates of mucositis and elevated creatinine levels compared to those on the 5-FU regimen, indicating a better safety profile for the taxane approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. Lee, B., Chehab, SS., Fan, W., et al.[2023]

The combination of carboplatin, oral tegafur, and cetuximab is a safe and well-tolerated first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), with a high compliance rate among patients.

In a study of 104 patients, the treatment resulted in a median overall survival of 11 months and a progression-free survival of 6 months, with an overall response rate of 35%, indicating its efficacy in managing this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. Buxó, E., Sosa, A., Reig, O., 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 II trial involving 32 patients with recurrent or metastatic head and neck squamous cell carcinoma, the combination of carboplatin and raltitrexed demonstrated moderate efficacy, with a 22% partial response rate and a median survival duration of 9.8 months.

The treatment was generally safe, with manageable toxicity; however, 25% of patients experienced severe neutropenia, and one patient dropped out due to persistent hepatic toxicity, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). Galetta, D., Giotta, F., Rosati, G., et al.[2014]

In a randomized trial involving 95 patients with stage IV-M0 head and neck cancer, the combination of cisplatin (CDDP) and fluorouracil (FU) was found to be more effective than carboplatin (CBDCA) and FU, with significantly better response rates and survival outcomes.

While CDDP-FU showed better efficacy, it was associated with higher rates of mucositis and vomiting, whereas CBDCA-FU led to more hematologic toxicity, indicating a trade-off in side effects between the two treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer. De Andrés, L., Brunet, J., López-Pousa, A., et al.[2017]

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]

The study evaluated the effectiveness of pembrolizumab and cetuximab, both alone and in combination, on head and neck squamous cell carcinoma (HNSCC) using the FLAVINO assay, revealing significant variability in patient responses, particularly in those with cisplatin-resistant cases.

An 'IP-10 score' was developed to predict patient outcomes based on their response to treatment, indicating that higher levels of IP-10 release in response to interferon gamma (IFN-γ) stimulation may correlate with better outcomes for certain HNSCC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. Berszin, M., Michaelides, I., Siemert, J., et al.[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]

A cost-effectiveness analysis of nivolumab versus pembrolizumab in treating platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) found that nivolumab has a 56% probability of being cost-effective at a willingness-to-pay (WTP) threshold of $100,000 per quality-adjusted life-year (QALY) when dosed at 3 mg/kg biweekly for patients under 72 kg.

For patients over this weight, pembrolizumab is generally the more cost-effective option, especially at higher WTP thresholds, indicating that patient body weight and dosing strategy are crucial factors in treatment decision-making.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. Pei, R., Shi, Y., Lv, S., et al.[2021]

References

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

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer. [2023]

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

Intravenous 5-Fluorouracil in Patients With Advanced Squamous Cell Carcinoma: A Retrospective Study. [2019]

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

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

4. Greece pubmed.ncbi.nlm.nih.gov

Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.). [2014]

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

Randomized trial of neoadjuvant cisplatin and fluorouracil versus carboplatin and fluorouracil in patients with stage IV-M0 head and neck cancer. [2017]

6. 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]

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

Phase I study of C-TPF in patients with locally advanced squamous cell carcinoma of the head and neck. [2018]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker. [2022]

9. 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]

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

Nivolumab vs Pembrolizumab for Treatment of US Patients With Platinum-Refractory Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Network Meta-analysis and Cost-effectiveness Analysis. [2021]