Head and Neck Cancer
Conditions
Keywords
Squamous cell carcinoma of the head and neck, programmed cell death protein 1 (PD-1) antibody, indoleamine 2,3-dioxygenase (IDO) inhibitor
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).
Interventions
DRUGNivolumab
Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.
DRUGEpacadostat
Epacadostat administered orally at the protocol-defined dose twice daily.
DRUGPlacebo
Matching placebo for epacadostat administered orally twice daily.
DRUGCarboplatin
Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.
DRUGCisplatin
Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.
DRUGCetuximab
Cetuximab administered intravenously at the protocol-defined dose weekly.
DRUG5-Fluorouracil
5-Fluorouracil administered intravenously at the protocol-defined dose on Days 1-4 for 6 cycles.
Sponsors
Bristol-Myers Squibb
Incyte Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
Outcome results
None listed