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

• Sponsor: Incyte Corporation (Industry)
• Overall Status: Withdrawn
• CT.gov ID: NCT03342352
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 0
• Arms: 3
• Actual Duration (Months): 4.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: Nivolumab; Drug: Epacadostat; Drug: Placebo; Drug: Carboplatin; Drug: Cisplatin; Drug: Cetuximab; Drug: 5-Fluorouracil	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 15, 2017
• Actual Primary Completion Date: Apr 20, 2018
• Actual Study Completion Date: Apr 20, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Incyte Corporation
• Bristol-Myers Squibb

Investigators

• Study Director: Vinny Hayreh, MD, Bristol-Myers Squibb Research and Development

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT03342352
• Other Study ID Numbers: CA2099NA/ECHO-310
• First Posted: Nov 14, 2017
• Last Update Posted: Dec 20, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Incyte Corporation: Squamous cell carcinoma of the head and neck; programmed cell death protein 1 (PD-1) antibody; indoleamine 2,3-dioxygenase (IDO) inhibitor
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carboplatin; Fluorouracil; Nivolumab; Cetuximab

Study Results

No Results Posted as of Dec 20, 2019