Pembrolizumab + Epacadostat for Head and Neck Cancer

Not currently recruiting at 92 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests treatments for people with recurrent or metastatic head and neck cancer. It evaluates the effectiveness of a new drug combination, pembrolizumab with epacadostat (an IDO inhibitor), compared to pembrolizumab alone and the standard EXTREME regimen, which includes a mix of chemotherapy drugs. Suitable participants have head and neck squamous cell carcinoma and can provide a tumor sample for study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that using pembrolizumab with epacadostat is generally safe for people with head and neck cancer. Previous studies found that this combination has a manageable safety profile, meaning most patients did not experience severe side effects. The data monitoring committee identified no safety issues with this combination.

For pembrolizumab alone, studies have shown it is well-tolerated by patients with head and neck cancer. No new safety concerns have been identified, so it is generally considered safe to use.

For those considering joining a trial with these treatments, existing evidence suggests a good safety record for both the combination and pembrolizumab alone. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Pembrolizumab and the combination of Pembrolizumab + Epacadostat for treating head and neck cancer because these treatments offer unique mechanisms of action compared to standard chemotherapy regimens like EXTREME, which uses cetuximab, cisplatin, carboplatin, and 5-fluorouracil. Pembrolizumab is an immunotherapy drug that boosts the immune system's ability to detect and fight cancer cells by targeting a protein called PD-1. When combined with Epacadostat, which inhibits the IDO1 enzyme that helps tumors evade immune detection, there's potential for a more robust immune response against cancer cells. This combination could offer a more targeted approach with possibly fewer side effects than traditional chemotherapy, making it a promising alternative for patients.

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

Research has shown that using pembrolizumab with epacadostat, one of the treatment arms in this trial, may effectively treat head and neck cancers. Early studies found that this combination is generally well-tolerated and shows promising results in patients with advanced solid tumors. Another arm of this trial involves pembrolizumab alone, which several studies have proven to help people with head and neck cancer live longer. The EXTREME regimen, including cetuximab, cisplatin or carboplatin, and 5-fluorouracil, is a well-known standard treatment for head and neck cancers and serves as the active comparator in this trial. These findings suggest that pembrolizumab, either alone or with epacadostat, could be a good treatment option for those with recurring or spreading head and neck squamous cell carcinoma. ^{1 2 4 6 7}

Who Is on the Research Team?

Mark Jones, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

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

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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 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 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]

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]

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]

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]

Citations

1. 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.

2. 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 ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02252042?tab=results

Study Results | Pembrolizumab (MK-3475) Versus ... Comparing programmed death ligand 1 scores for predicting pembrolizumab efficacy in head and neck cancer. Mod Pathol. 2021 Mar;34(3):532-541. doi: 10.1038 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0959804925001765

5-year follow-up from the randomized phase III KEYNOTE- ... Previous results of the phase 3 KEYNOTE-048 study showed that pembrolizumab significantly improved overall survival (OS) compared with cetuximab ...

5. merck.com merck.com/news/mercks-keytruda-pembrolizumab-significantly-improved-overall-survival-compared-to-standard-of-care-as-monotherapy-and-in-combination-with-chemotherapy-as-first-line-treatment-for-patients/

Merck's KEYTRUDA (pembrolizumab) Significantly ... “In this study, KEYTRUDA showed the potential to significantly prolong survival when used as first-line therapy for patients whose head and neck cancer had ...

6. clinicaltrialsarena.com clinicaltrialsarena.com/news/msd-keytruda-combo/

MSD reports outcomes from trial of Keytruda combination ... After a median follow-up at 38.3 months, the therapy had decreased the EFS event risk by 34% in subjects whose combined positive score (CPS) was ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.21.02508

Updated Results of the Phase III KEYNOTE-048 Study Pembrolizumab-chemotherapy significantly prolonged OS compared with cetuximab-chemotherapy in all cohorts (PD-L1 CPS ≥ 20, HR, 0.60, 95% CI, ...