Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 3 Randomized, Open-Label Clinical Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen as First Line Treatment for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Epacadostat
* Drug: Cetuximab
* Drug: Cisplatin
* Drug: Carboplatin
* Drug: 5-Fluorouracil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Measurable disease based on RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate organ function per protocol-defined criteria. Documentation of results from testing of human papilloma virus (HPV) status for oropharyngeal cancer. Baseline archival tumor specimen available or willing to undergo a prestudy treatment tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain the specimen. Exclusion Criteria: Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors. Disease progression within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC. Use of protocol-defined prior/concomitant therapy. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Active autoimmune disease that has required systemic treatment in past 2 years. Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority. Known history of or is positive for active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (defined as HCV RNA [qualitative] is detected).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab + Epacadostat<br> | Drug: Pembrolizumab<br>* Pembrolizumab administered intravenously every 3 weeks.<br>* Other names: MK-3475;Drug: Epacadostat<br>* Epacadostat administered orally twice daily.<br>* Other names: INCB024360;|
| Experimental: Pembrolizumab<br> | Drug: Pembrolizumab<br>* Pembrolizumab administered intravenously every 3 weeks.<br>* Other names: MK-3475;|
| Active Comparator: EXTREME<br>EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. | Drug: Cetuximab<br>* Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously every 3 weeks for </= 6 cycles.<br>Drug: Carboplatin<br>* Carboplatin administered intravenously every 3 weeks for </= 6 cycles.<br>Drug: 5-Fluorouracil<br>* 5-Fluorouracil administered intravenously every 3 weeks for </= 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen | ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination. Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans. | Minimum Week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs) | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months. | Up to 14 months | 
| Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs | AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months. | Up to 14 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and neck squamous cell carcinoma, programmed cell death 1 (PD-1) inhibitor, indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor