Nivolumab Plus Epacadostat in Combination With Chemotherapy Versus the EXTREME Regimen in Squamous Cell Carcinoma of the Head and Neck (CheckMate 9NA/ECHO-310)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the safety and efficacy of the combination of nivolumab plus epacadostat in combination with chemotherapy in first-line recurrent or metastatic patients with squamous cell carcinoma of the head and neck (SCCHN) when compared to the standard of care (EXTREME regimen).

Official Title
-----------------
A Randomized, Global, Phase 3 Trial of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Platinum + 5-fluorouracil) Versus the EXTREME Regimen (Cetuximab + Platinum + 5-fluorouracil) in First-line Treatment of Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) / CheckMate 9NA /ECHO-310

Conditions
-----------------
Head and Neck Cancer

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed SCCHN from any of the following primary sites: oral cavity, oropharynx, hypopharynx, and larynx. Must have recurrent or metastatic disease that is not amenable to therapy with curative intent (surgery and/or radiation therapy with or without chemotherapy). No prior treatment with systemic anti-cancer therapy for SCCHN unless protocol-defined conditions are met. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to1. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1. Documentation of program death ligand-1 (PD-L1) status prior to randomization. Exclusion Criteria: Recurrent or metastatic carcinoma of the nasopharynx and paranasal sinuses, squamous cell carcinoma that originated from the skin and salivary gland or non-squamous histologies (e.g., mucosal melanoma) and SCCHN of unknown primary origin. Untreated central nervous system (CNS) metastases. Carcinomatous meningitis. Active, known or suspected autoimmune disease. Physical and laboratory test findings outside the protocol-defined range.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil. | Drug: Nivolumab<br>* Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.<br>Drug: Epacadostat<br>* Epacadostat administered orally at the protocol-defined dose twice daily.<br>* Other names: INCB024360;Drug: Carboplatin<br>* Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.<br>Drug: 5-Fluorouracil<br>* 5-Fluorouracil administered intravenously at the protocol-defined dose on Days 1-4 for 6 cycles.<br>|
| Active Comparator: Arm B<br>EXTREME regimen. | Drug: Carboplatin<br>* Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.<br>Drug: Cetuximab<br>* Cetuximab administered intravenously at the protocol-defined dose weekly.<br>Drug: 5-Fluorouracil<br>* 5-Fluorouracil administered intravenously at the protocol-defined dose on Days 1-4 for 6 cycles.<br>|
| Experimental: Arm C<br>Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil. | Drug: Nivolumab<br>* Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.<br>Drug: Placebo<br>* Matching placebo for epacadostat administered orally twice daily.<br>Drug: Carboplatin<br>* Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.<br>Drug: Cisplatin<br>* Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.<br>Drug: 5-Fluorouracil<br>* 5-Fluorouracil administered intravenously at the protocol-defined dose on Days 1-4 for 6 cycles.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B) | Defined as the time between the date of randomization and the date of first documented disease progression (per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) or death due to any cause, whichever occurs first. | Up to approximately 35 months | 
| Overall survival (OS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B) | Defined as the time between the date of randomization and the date of death. | Up to approximately 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B) | Defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. | Up to approximately 35 months | 
| Duration of response (DOR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B) | Defined as the time between the date of first documented response (CR or PR per RECIST v1.1) to the date of the first disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first. | Up to approximately 35 months | 
| ORR with nivolumab plus placebo in combination with chemotherapy (Arm C) | Defined as the number of participants with a best overall response of complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. | Up to approximately 35 months | 
| PFS with nivolumab plus placebo in combination with chemotherapy (Arm C) | Defined as the time between the date of randomization and the date of first documented disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first. | Up to approximately 35 months | 
| DOR with nivolumab plus placebo in combination with chemotherapy (Arm C) | Defined as the time between the date of first documented response (CR or PR per RECIST v1.1) to the date of the first disease progression (per RECIST v1.1) or death due to any cause, whichever occurs first. | Up to approximately 35 months | 
| Time to meaningful symptomatic deterioration (TTSD) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B) | TTSD assessed by the 10-item Functional Assessment of Cancer Therapy-Head & Neck (FACT-HN) Symptom Index (FHNSI-10). | Up to approximately 60 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Squamous cell carcinoma of the head and neck, programmed cell death protein 1 (PD-1) antibody, indoleamine 2,3-dioxygenase (IDO) inhibitor