A Phase 3 randomized clinical Study of Pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen as first line treatment for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Start 9 Jan 2018 · End 31 Oct 2025 · Status Ended · 2 EU/EEA countries · 3 sites · Protocol MK-3475-669

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ended

Participants planned 42

Countries 2

Sites 3

Histologically or cytologically-confirmed Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma that is considered incurable by local therapies

To estimate ORR of pembrolizumab + epacadostat, pembrolizumab monotherapy, and the EXTREME regimen based on RECIST 1.1 by investigator determination.

Key facts

Sponsor: Incyte Corp.
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Neoplasms [C04]
Trial duration: 9 Jan 2018 → 31 Oct 2025
Decision date (initial): 2024-06-11
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: No
Funding sources: Merck Sharp & Dohme LLC · Incyte Corp.

External identifiers

EU CT number: 2024-512015-47-00
EudraCT number: 2017-001338-24
WHO UTN: U1111-1301-4155
ClinicalTrials.gov: NCT03358472

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Therapy, Safety, Efficacy

To estimate ORR of pembrolizumab + epacadostat, pembrolizumab monotherapy, and the EXTREME regimen based on RECIST 1.1 by investigator determination.

Secondary objectives 1

To evaluate the safety and tolerability of the 3 treatment groups.

Conditions and MedDRA coding

Histologically or cytologically-confirmed Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma that is considered incurable by local therapies

Version	Level	Code	Term	System organ class
22.0	LLT	10082179	Squamous cell carcinoma of head and neck metastatic	10029104

Regulatory references

Scientific advice from competent authorities: European Medicines Agency
Plan to share IPD: Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

Participants with histologically or cytologically-confirmed recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that is considered incurable by local therapies. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
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 8

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 Head and Neck Squamous Cell Carcinoma (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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen

Secondary endpoints 2

Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323785 · Product

Active substance: Pembrolizumab
Substance synonyms: Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 200 mg milligram(s)
Max total dose: 7000 mg milligram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Authorised
ATC code: L01FF02 — -
Marketing authorisation: EU/1/15/1024/002
MA holder: MERCK SHARP & DOHME B.V.
MA country: Liechtenstein
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323786 · Product

Active substance: Pembrolizumab
Substance synonyms: Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 200 mg milligram(s)
Max total dose: 7000 mg milligram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Authorised
ATC code: L01FF02 — -
Marketing authorisation: EU/1/15/1024/002
MA holder: MERCK SHARP & DOHME B.V.
MA country: Norway
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323784 · Product

Active substance: Pembrolizumab
Substance synonyms: Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENIOUS INFUSION
Max daily dose: 200 mg milligram(s)
Max total dose: 7000 mg milligram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Authorised
ATC code: L01FF02 — -
Marketing authorisation: EU/1/15/1024/002
MA holder: MERCK SHARP & DOHME B.V.
MA country: Iceland
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

KEYTRUDA 25 mg/mL concentrate for solution for infusion

PRD4323105 · Product

Active substance: Pembrolizumab
Substance synonyms: Lambrolizumab, MK-3475, SCH-900475, BAT3306, Pabolizumab, FYB206, ABP 234
Pharmaceutical form: SOLUTION FOR INFUSION
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 200 mg milligram(s)
Max total dose: 7000 mg milligram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Authorised
ATC code: L01FF02 — -
Marketing authorisation: EU/1/15/1024/002
MA holder: MERCK SHARP & DOHME B.V.
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Epacadostat

PRD11190667 · Product

Active substance: Epacadostat
Substance synonyms: INCB024360
Pharmaceutical form: TABLET
Route of administration: ORAL
Max daily dose: 200 mg milligram(s)
Max total dose: 7000 mg milligram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Not Authorised
MA holder: INCYTE CORPORATION
Paediatric formulation: No
Orphan designation: No

Epacadostat

PRD11190666 · Product

Active substance: Epacadostat
Substance synonyms: INCB024360
Pharmaceutical form: TABLET
Route of administration: ORAL
Max daily dose: 200 mg milligram(s)
Max total dose: 7000 mg milligram(s)
Max treatment duration: 24 Month(s)
Authorisation status: Not Authorised
MA holder: INCYTE CORPORATION
Paediatric formulation: No
Orphan designation: No

Comparator 4

Fluorouracil

SCP1165178 · ATC

Active substance: Fluorouracil
Substance synonyms: 5-FLOUROURACIL, 5-FLUORO-1H-PYRIMIDINE-2,4-DIONE, 5-FLUOROURACIL, 5-FU
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 1000 mg/m2 milligram(s)/sq. meter
Max total dose: 6000 mg/m2 milligram(s)/sq. meter
Max treatment duration: 18 Week(s)
Authorisation status: Authorised
ATC code: L01BC02 — FLUOROURACIL
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Carboplatin

SCP10337134 · ATC

Active substance: Carboplatin
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 5 Other
Max total dose: 30 Other
Max treatment duration: 18 Week(s)
Authorisation status: Authorised
ATC code: L01XA02 — CARBOPLATIN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cisplatin

SCP134220 · ATC

Active substance: Cisplatin
Substance synonyms: Cis-diamminedichloroplatinum, (SP-4-2)-cis -diamminedichloroplatinum, CDDP
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 100 mg/m2 milligram(s)/sq. meter
Max total dose: 600 mg/m2 milligram(s)/sq. meter
Max treatment duration: 18 Week(s)
Authorisation status: Authorised
ATC code: L01XA01 — CISPLATIN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Cetuximab

SCP185672 · ATC

Active substance: Cetuximab
Route of administration: INTRAVENOUS INFUSION
Max daily dose: 400 mg/m2 milligram(s)/sq. meter
Max total dose: 26400 mg/m2 milligram(s)/sq. meter
Max treatment duration: 24 Month(s)
Authorisation status: Authorised
ATC code: L01FE01 — CETUXIMAB
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation: Incyte Corp.
Address: 1801 Augustine Cut Off
City: Wilmington
Postcode: 19803-4404
Country: United States

Scientific contact point

Organisation: Incyte Corp.
Contact name: Nirosh Naicker

Public contact point

Organisation: Incyte Corp.
Contact name: Nirosh Naicker

Third parties 3

Organisation	City, country	Duties
Merck Sharp & Dohme LLC ORG-100006323	Rahway, United States	On site monitoring, Code 10, Code 11, Code 12, Code 13, Code 14, Code 2, Interactive response technologies (IRT), Laboratory analysis, Code 5, Data management, E-data capture, Code 8, Code 9
Almac Clinical Technologies LLC ORG-100043036	Souderton, United States	Interactive response technologies (IRT)
Parexel International Corp. ORG-100007310	Auburndale, United States	Other

Locations

2 EU/EEA countries · 3 investigational sites

By country

Country	MS status	Planned subjects	Sites
Portugal	Ended	6	1
Spain	Ended	36	2
Rest of world	—	0	—

Investigational sites

Portugal

1 site · Ended

Instituto Portugues De Oncologia De Coimbra Francisco Gentil E.P.E.

Serviço de Oncologia Médica, Avenida Doutor Bissaya Barreto 98, 3000-075, Coimbra

Spain

2 sites · Ended

Hospital Universitari Vall D Hebron

Servicio de Oncología, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona

Institut Catala D'oncologia

Servicio de Oncología, Carretera Canyet S/n, 08916, Badalona

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
Portugal	2018-01-11	2025-10-20	2018-02-06	2018-05-01
Spain	2018-01-09	2025-10-30	2018-01-11	2018-05-01

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 19 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Protocol (for publication)	D1_Delegation of Authority_ESP_for pub	outofscope
Protocol (for publication)	D1_Delegation of Authority_PRT_for pub	outofscope
Protocol (for publication)	D1_Protocol_2023-510177-33_for pub	06
Recruitment arrangements (for publication)	K1_Recruitment Arragements and IC Procedure_ESP_ES_for pub	13SEP2017R
Recruitment arrangements (for publication)	K1_Recruitment Arrangements_PRT_PT_for pub	10OCT2017
Subject information and informed consent form (for publication)	L1_ICF_Genetic consent_1203_PRT_PT_for pub	0.01
Subject information and informed consent form (for publication)	L1_ICF_Main addendum adult consent_ESP_ES_SM01_for pub	01
Subject information and informed consent form (for publication)	L1_ICF_Main consent_1203_PRT_PT_for pub	AM03v3.03
Subject information and informed consent form (for publication)	L1_ICF_Main consent_ESP_ES_for pub	AM03_3.02
Subject information and informed consent form (for publication)	L1_ICF_Optional_addendum_progression consent_1203_PRT_PT_SM01_for pub	0.01
Subject information and informed consent form (for publication)	L1_ICF_Optional_withdrawal_1203_PRT_PT_for pub	0.01
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC RSI_5-FLUOROURACIL_SM01_for pub	Hospira UK
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC RSI_CARBOPLATIN_SM01_for pub	Hospira UK
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC RSI_CETUXIMAB_SM01_for pub	Merck Sero
Summary of Product Characteristics (SmPC) (for publication)	E2_SmPC RSI_CISPLATIN_SM01_for pub	Sandoz Lim
Synopsis of the protocol (for publication)	D1_PPLS_2024-512015-47_ESP_ES_SM01_for pub	1.0
Synopsis of the protocol (for publication)	D1_PPLS_2024-512015-47_SM01_for pub	1.0
Synopsis of the protocol (for publication)	D1_Protocol Scientific Synopsis_2024-512015-47_ESP_ES_for pub	06
Synopsis of the protocol (for publication)	D1_Protocol Scientific Synopsis_2024-512015-47_PRT_PT_for pub	06

Application history

3 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2024-05-07	Portugal	Acceptable 2024-06-11	2024-06-11
2	NON SUBSTANTIAL MODIFICATION	NSM-1	2024-11-28	Portugal	Acceptable 2024-06-11	2024-11-28
3	SUBSTANTIAL MODIFICATION	SM-1	2025-01-13	Portugal	Acceptable 2025-03-17	2025-03-17

A Phase 3 randomized clinical Study of Pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen as first line treatment for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

Overview

Key facts

External identifiers

Trial design

Main objective

Secondary objectives 1

Conditions and MedDRA coding

Regulatory references

Eligibility criteria

Inclusion criteria 6

Exclusion criteria 8

Endpoints

Primary endpoints 1

Secondary endpoints 2

Investigational products

Test 6

Comparator 4

Sponsors and contacts

Incyte Corp.

Scientific contact point

Public contact point

Third parties 3

Locations

By country

Investigational sites

Country notifications

Results and documents

Documents 19 files

Application history

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