Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy... | NCT03358472

NCT03358472

ID	Type	Description	Link
2017-001338-24	EudraCT Number

Status Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Label	Type	Description	Intervention Names
Pembrolizumab + Epacadostat	Experimental		Drug: Pembrolizumab Drug: Epacadostat
Pembrolizumab	Experimental		Drug: Pembrolizumab
EXTREME	Active Comparator	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil.	Drug: Cetuximab Drug: Cisplatin Drug: Carboplatin Drug: 5-Fluorouracil

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Drug	Pembrolizumab administered intravenously every 3 weeks.	Pembrolizumab Pembrolizumab + Epacadostat

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen	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.	Minimum Week 9

Secondary Outcomes

Measure	Description	Time Frame
Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)	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.

Eligibility Module

Name	Affiliation	Role
Mark Jones, MD	Incyte Corporation	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pacific Cancer Medical Center		Anaheim	California	19026	United States
UC Davis Comprehensive Cancer Center

PubMed Identifier	Type	Citation	Retractions
39054467	Derived	Cho BC, Brana I, Cirauqui B, Aksoy S, Couture F, Hong RL, Miller WH Jr, Chaves-Conde M, Teixeira M, Leopold L, Munteanu M, Ge JY, Swaby RF, Hughes BGM. Pembrolizumab plus epacadostat in patients with recurrent/metastatic head and neck squamous cell carcinoma (KEYNOTE-669/ECHO-304): a phase 3, randomized, open-label study. BMC Cancer. 2024 Jul 25;23(Suppl 1):1254. doi: 10.1186/s12885-023-11316-0.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pembrolizumab + Epacadostat	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
FG001	Pembrolizumab	Pembrolizumab administered intravenously every 3 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 12, 2018

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

The Intention-to-Treat (ITT) population consisted of all randomized participants.

The ORR was based on all available imaging assessments after the last participant completed the Week 9 imaging assessment by investigator determination.

Posted

Number

95% Confidence Interval

percentage of participants

Minimum Week 9

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
OG001	Pembrolizumab	Pembrolizumab administered intravenously every 3 weeks.
OG002	EXTREME	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for \

Units	Counts
Participants	OG00035 OG00119 OG00235

Title

Denominators

Categories

Title	Measurements
	OG00031.4(16.9 to 49.3) OG00121.1(6.1 to 45.6) OG00234.3(19.1 to 52.2)

Secondary

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

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.

All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Up to 14 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
OG001	Pembrolizumab	Pembrolizumab administered intravenously every 3 weeks.
OG002	EXTREME	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for \

Secondary

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

Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months.

All Participants as Treated (APaT) population consisted of all randomized participants who received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Up to 14 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
OG001	Pembrolizumab	Pembrolizumab administered intravenously every 3 weeks.
OG002	EXTREME	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for \

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Myocardial infarction	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Colitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Localised oedema	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Oedema	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Bacterial infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Catheter site infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Cellulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Clostridial sepsis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Empyema	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Lung infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Osteomyelitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Sepsis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Traumatic haemothorax	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Blood creatinine increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Cerebral infarction	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Syncope	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0005 affected34 at risk EG0014 affected19 at risk EG00219 affected34 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG00213 affected34 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0029 affected34 at risk
Pericardial effusion	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Hypothyroidism	Endocrine disorders	MedDRA 21.1	Systematic Assessment	EG0006 affected34 at risk EG0014 affected19 at risk EG0021 affected34 at risk
Eyelid oedema	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Lacrimation increased	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Ankyloglossia acquired	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Cheilosis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Constipation	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0006 affected34 at risk EG0011 affected19 at risk EG00212 affected34 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0007 affected34 at risk EG0012 affected19 at risk EG0027 affected34 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Nausea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0005 affected34 at risk EG0012 affected19 at risk EG00217 affected34 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Oral pain	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0010 affected19 at risk EG0028 affected34 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0007 affected34 at risk EG0010 affected19 at risk EG0025 affected34 at risk
Asthenia	General disorders	MedDRA 21.1	Systematic Assessment	EG0006 affected34 at risk EG0012 affected19 at risk EG0028 affected34 at risk
Chest pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0012 affected19 at risk EG0022 affected34 at risk
Face oedema	General disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG00011 affected34 at risk EG0013 affected19 at risk EG0027 affected34 at risk
Malaise	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Mucosal inflammation	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG00210 affected34 at risk
Oedema peripheral	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Pyrexia	General disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0010 affected19 at risk EG0025 affected34 at risk
Swelling	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Ulcer	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Bronchitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Conjunctivitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Device related infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Cellulitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Nasopharyngitis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0013 affected19 at risk EG0023 affected34 at risk
Oral candidiasis	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Paronychia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0029 affected34 at risk
Pneumonia	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Urinary tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Wound infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Alanine aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0011 affected19 at risk EG0025 affected34 at risk
Amylase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0004 affected34 at risk EG0011 affected19 at risk EG0022 affected34 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0011 affected19 at risk EG0024 affected34 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0012 affected19 at risk EG0021 affected34 at risk
Blood bilirubin increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Blood creatinine increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0011 affected19 at risk EG0023 affected34 at risk
Blood glucose increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Blood potassium decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Blood sodium decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Lipase increased	Investigations	MedDRA 21.1	Systematic Assessment	EG0006 affected34 at risk EG0010 affected19 at risk EG0024 affected34 at risk
Lymphocyte count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Neutrophil count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0028 affected34 at risk
Platelet count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG00212 affected34 at risk
Weight decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0012 affected19 at risk EG0028 affected34 at risk
White blood cell count decreased	Investigations	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0027 affected34 at risk
Cachexia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0012 affected19 at risk EG0029 affected34 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0012 affected19 at risk EG0021 affected34 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0022 affected34 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0022 affected34 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0024 affected34 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0029 affected34 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0012 affected19 at risk EG0022 affected34 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0012 affected19 at risk EG0021 affected34 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0004 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0023 affected34 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0012 affected19 at risk EG0021 affected34 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Aphonia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Dizziness	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Dysgeusia	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0024 affected34 at risk
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0012 affected19 at risk EG0021 affected34 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Tremor	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Anxiety	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Confusional state	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Insomnia	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0005 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Glycosuria	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Urinary tract disorder	Renal and urinary disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Gynaecomastia	Reproductive system and breast disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0013 affected19 at risk EG0021 affected34 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0003 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0006 affected34 at risk EG0011 affected19 at risk EG0022 affected34 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0004 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0023 affected34 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0021 affected34 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Tracheal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0020 affected34 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG00214 affected34 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0022 affected34 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0007 affected34 at risk EG0010 affected19 at risk EG0026 affected34 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0009 affected34 at risk EG0014 affected19 at risk EG00213 affected34 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0010 affected19 at risk EG0023 affected34 at risk
Skin haemorrhage	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0012 affected19 at risk EG0020 affected34 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Circulatory collapse	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0000 affected34 at risk EG0011 affected19 at risk EG0020 affected34 at risk
Hypertension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0001 affected34 at risk EG0012 affected19 at risk EG0023 affected34 at risk
Hypotension	Vascular disorders	MedDRA 21.1	Systematic Assessment	EG0002 affected34 at risk EG0010 affected19 at risk EG0021 affected34 at risk

ID	Term
D006258	Head and Neck Neoplasms
D000077195	Squamous Cell Carcinoma of Head and Neck
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D056831	Coordination Complexes
D009930	Organic Chemicals
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Pembrolizumab + Epacadostat	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.
BG001	Pembrolizumab	Pembrolizumab administered intravenously every 3 weeks.
BG002	EXTREME	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for \
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab + Epacadostat	Pembrolizumab administered intravenously every 3 weeks. Epacadostat administered orally twice daily.	6	35	12	34	34	34
EG001	Pembrolizumab	Pembrolizumab administered intravenously every 3 weeks.	4	19	8	19	17	19
EG002	EXTREME	EXTREME regimen includes cetuximab + cisplatin or carboplatin + 5-fluorouracil. Cetuximab administered intravenously on Cycle 1 Day 1 followed by administration every week. Cisplatin administered intravenously every 3 weeks for \	10	35	12	34	34	34

ID	Term
C582435	pembrolizumab
C000613752	epacadostat
D000068818	Cetuximab
D002945	Cisplatin
D016190	Carboplatin
D005472	Fluorouracil