Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)

Phase 3

Active, not recruiting

• Conditions: Head and Neck Cancer
• Interventions: Drug: Pembrolizumab; Drug: Cetuximab; Drug: Epacadostat; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil

• Registration Number: NCT03358472
• Lead Sponsor: Incyte Corporation

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab + cisplatin or carboplatin + 5-fluorouracil) as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-27
• Study First Submitted QC: 2017-11-27
• Study First Posted: 2017-11-30
• Study Start: 2017-12-01
• Primary Completion: 2018-07-19
• Results First Submitted: 2019-07-19
• Results First Submitted QC: 2019-08-19
• Results First Posted: 2019-09-10
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-03
• Study Completion: 2025-12-19

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 89

Inclusion Criteria

• Measurable disease based on RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function per protocol-defined criteria.
• Documentation of results from testing of human papilloma virus (HPV) status for oropharyngeal cancer.
• Baseline archival tumor specimen available or willing to undergo a prestudy treatment tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain the specimen.

Exclusion Criteria

• Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors.
• Disease progression within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.
• Use of protocol-defined prior/concomitant therapy.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Active autoimmune disease that has required systemic treatment in past 2 years.
• Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by local health authority.
• Known history of or is positive for active hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (defined as HCV RNA [qualitative] is detected).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pembrolizumab + Epacadostat	Epacadostat	-
Pembrolizumab + Epacadostat	Pembrolizumab	-
EXTREME	Cetuximab	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.
Pembrolizumab	Pembrolizumab	-
EXTREME	Cisplatin	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.
EXTREME	Carboplatin	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.
EXTREME	5-Fluorouracil	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen	Minimum Week 9	ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), \>=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.; Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans.

Secondary Outcome Measures

Name	Time	Method
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)	Up to 14 months	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.; Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs	Up to 14 months	AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.; Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.

Trial Locations

Locations (73)

Pacific Cancer Medical Center; 🇺🇸 Anaheim, California, United States

UC Davis Comprehensive Cancer Center; 🇺🇸 Sacramento, California, United States

St. Joseph Heritage Healthcare; 🇺🇸 Santa Rosa, California, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Northwest Georgia Oncology Centers PC; 🇺🇸 Douglasville, Georgia, United States

U of Kansas Cancer Center; 🇺🇸 Westwood, Kansas, United States

Baptist Health; 🇺🇸 Louisville, Kentucky, United States

St. Vincent Healthcare Cancer Ctr; 🇺🇸 Billings, Montana, United States

New Mexico Cancer Care Alliance; 🇺🇸 Albuquerque, New Mexico, United States

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