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
Overview
- Phase
- Phase 3
- Intervention
- Nivolumab
- Conditions
- Head and Neck Cancer
- Sponsor
- Incyte Corporation
- Primary Endpoint
- Overall survival (OS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
- Status
- Withdrawn
- Last Updated
- 6 years ago
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).
Investigators
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 to
- •Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.
- •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.
Arms & Interventions
Arm A
Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Nivolumab
Arm A
Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Epacadostat
Arm A
Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Carboplatin
Arm A
Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Cisplatin
Arm A
Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: 5-Fluorouracil
Arm B
EXTREME regimen.
Intervention: Carboplatin
Arm B
EXTREME regimen.
Intervention: Cisplatin
Arm B
EXTREME regimen.
Intervention: Cetuximab
Arm B
EXTREME regimen.
Intervention: 5-Fluorouracil
Arm C
Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Nivolumab
Arm C
Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Placebo
Arm C
Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Carboplatin
Arm C
Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: Cisplatin
Arm C
Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Intervention: 5-Fluorouracil
Outcomes
Primary Outcomes
Overall survival (OS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
Time Frame: Up to approximately 48 months
Defined as the time between the date of randomization and the date of death.
Progression-free survival (PFS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)
Time Frame: Up to approximately 35 months
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.
Secondary Outcomes
- PFS with nivolumab plus placebo in combination with chemotherapy (Arm C)(Up to approximately 35 months)
- DOR with nivolumab plus placebo in combination with chemotherapy (Arm C)(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)(Up to approximately 60 months)
- Duration of response (DOR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B)(Up to approximately 35 months)
- Objective response rate (ORR) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) and the EXTREME regimen (Arm B)(Up to approximately 35 months)
- ORR with nivolumab plus placebo in combination with chemotherapy (Arm C)(Up to approximately 35 months)