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

Phase 3
Withdrawn
Conditions
Head and Neck Cancer
Interventions
Registration Number
NCT03342352
Lead Sponsor
Incyte Corporation
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).

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm CPlaceboNivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm BCarboplatinEXTREME regimen.
Arm CCarboplatinNivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm ANivolumabNivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm AEpacadostatNivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm ACarboplatinNivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm A5-FluorouracilNivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm ACisplatinNivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm BCisplatinEXTREME regimen.
Arm BCetuximabEXTREME regimen.
Arm B5-FluorouracilEXTREME regimen.
Arm CNivolumabNivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm CCisplatinNivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Arm C5-FluorouracilNivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.
Primary Outcome Measures
NameTimeMethod
Overall survival (OS) with nivolumab plus epacadostat in combination with chemotherapy (Arm A) compared to the EXTREME regimen (Arm B)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)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 Outcome Measures
NameTimeMethod
PFS with nivolumab plus placebo in combination with chemotherapy (Arm C)Up to approximately 35 months

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.

DOR with nivolumab plus placebo in combination with chemotherapy (Arm C)Up to approximately 35 months

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.

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

TTSD assessed by the 10-item Functional Assessment of Cancer Therapy-Head \& Neck (FACT-HN) Symptom Index (FHNSI-10).

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

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.

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

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.

ORR with nivolumab plus placebo in combination with chemotherapy (Arm C)Up to approximately 35 months

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.

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