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

NCT03342352 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: CA2099NA/ECHO-310
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Head and Neck Cancer

Keywords

Squamous cell carcinoma of the head and neck; programmed cell death protein 1 (PD-1) antibody; indoleamine 2,3-dioxygenase (IDO) inhibitor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• 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

• 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

• ORR with nivolumab plus placebo in combination with chemotherapy (Arm C)

  Up to approximately 35 months

• 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

Study Arms (3)

Arm A

EXPERIMENTAL

Nivolumab plus epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.

Drug: Nivolumab; Drug: Epacadostat; Drug: Carboplatin; Drug: Cisplatin; Drug: 5-Fluorouracil

Arm B

ACTIVE COMPARATOR

EXTREME regimen.

Drug: Carboplatin; Drug: Cisplatin; Drug: Cetuximab; Drug: 5-Fluorouracil

Arm C

EXPERIMENTAL

Nivolumab plus placebo for epacadostat in combination with platinum (carboplatin/cisplatin) plus 5-fluorouracil.

Drug: Nivolumab; Drug: Placebo; Drug: Carboplatin; Drug: Cisplatin; Drug: 5-Fluorouracil

Interventions

Nivolumab DRUG

Nivolumab administered intravenously at the protocol-defined dose every 3 weeks.

Arm A; Arm C

Epacadostat DRUG

Epacadostat administered orally at the protocol-defined dose twice daily.

Also known as: INCB024360

Arm A

Placebo DRUG

Matching placebo for epacadostat administered orally twice daily.

Arm C

Carboplatin DRUG

Carboplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.

Arm A; Arm B; Arm C

Cisplatin DRUG

Cisplatin administered intravenously at the protocol-defined dose every 3 weeks for 6 cycles.

Arm A; Arm B; Arm C

Cetuximab DRUG

Cetuximab administered intravenously at the protocol-defined dose weekly.

Arm B

5-Fluorouracil DRUG

5-Fluorouracil administered intravenously at the protocol-defined dose on Days 1-4 for 6 cycles.

Arm A; Arm B; Arm C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Incyte Corporation: lead
• Bristol-Myers Squibb: collaborator

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

Nivolumab; epacadostat; Carboplatin; Cisplatin; Cetuximab; Fluorouracil

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Vinny Hayreh, MD

  Bristol-Myers Squibb Research and Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2017
• First Posted: November 14, 2017
• Study Start: December 15, 2017
• Primary Completion: April 20, 2018
• Study Completion: April 20, 2018
• Last Updated: December 20, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share