Study to Evaluate Erlotinib With or Without SNDX-275 (Ent... | NCT00602030

Label	Type	Description	Intervention Names
Lead-in Phase: Erlotinib + Entinostat 5 mg	Experimental	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.	Drug: Entinostat Drug: Erlotinib
Lead-in Phase: Erlotinib + Entinostat 10 mg	Experimental	Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.	Drug: Entinostat Drug: Erlotinib
Double-blind Phase: Erlotinib + Entinostat 10 mg	Experimental	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.	Drug: Entinostat Drug: Erlotinib
Double-blind Phase: Erlotinib + Placebo	Placebo Comparator	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.	Drug: Placebo Drug: Erlotinib

Name	Type	Description	Arm Group Labels	Other Names
Entinostat	Drug	Entinostat tablets on Days 1 and 15 of a 28-day cycle.	Crossover Phase: Erlotinib + Entinostat 10 mg Double-blind Phase: Erlotinib + Entinostat 10 mg

Measure	Description	Time Frame
Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase	Safe recommended Phase 2 dose was determined based on dose-limiting toxicities (DLT) in Cycle 1. A DLT was defined as any of the following occurring in Cycle 1: Grade 3 or greater nonhematologic toxicity that was considered related to either entinostat or erlotinib or a Grade 4 hematologic toxicity lasting more than 7 days and/or resulting in a dose delay. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale was used where Grade 1=mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=life-threatening and 5=death. The dose that was found to be safe is reported.	Cycle 1 of Lead-in Phase
4-Month Progression-free Survival (PFS) Rate in the Double-blind Phase	PFS rate at 4 months was defined as the percentage of participants who are progression-free at 4 months.	Month 4

Measure	Description	Time Frame
Objective Response Rate (ORR) in the Double-blind Phase	ORR was defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) as assessed by the investigator. CR=disappearance of all target lesions; disappearance of non-target lesions and normalization of tumor marker level. PR=At least a 30% decrease in the sum of the longest diameter of target lesions, taking at reference the baseline sum longest diameter.

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Cytologically or histologically confirmed NSCLC of stage IIIb or IV
Received at least 1 but no more than 2 prior chemotherapy or chemoradiotherapy regimens for advanced NSCLC (that did not include erlotinib and valproic acid) and progressed based on radiologic evidence
At least 1 measurable lesion by conventional or spiral computed tomography (CT) scan
Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 and life expectancy of at least 6 months
Paraffin-embedded tumor specimen available for correlative studies
Male or female over 18 years of age
Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x 10^9/L; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L without the use of hematopoietic growth factors
Bilirubin and creatinine less than 2 times the upper limit of normal for the institution
Albumin ≥ 2.5 g/dL
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times the upper limit of normal for the institution
Prothrombin time less than 1.5 times the upper limit of normal for the institution
Potassium, magnesium and phosphorus within the normal range for the institution (supplementation is permissible)
Willing to use accepted and effective methods of contraception during the study (both men and women as appropriate) and for 3 months after the last dose of SNDX-275
Patient or legally acceptable representative has granted written informed consent before any study-specific procedure (including special screening tests) are performed

Exclusion Criteria

Prior stem cell transplant
Clinical evidence of central nervous system (CNS) involvement
Prior treatment with an histone deacetylase (HDAC) inhibitor or an epidermal growth factor receptor (EGFR) inhibitor
Currently taking known inhibitors of CYPA4, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, ≥ 10 mg prednisone, and voriconazole
Currently taking medication(s) on the prohibited medication list
Prior exposure to SNDX-275
Systemic chemotherapy, radiotherapy, or treatment with an investigational agent without recovery to at least grade 1 or baseline before study drug administration
Daily treatment with ≥ 10 mg prednisone within 28 days before study drug administration
Local or whole brain palliative radiotherapy within 14 days before study drug administration
Currently active second malignancy, or any malignancy within the last 5 years other than cured basal or squamous cell skin carcinoma, cervical carcinoma in situ, carcinoma in situ of the bladder, or papillary thyroid cancer
Inability to swallow oral medications or a gastrointestinal malabsorption condition
Acute infection requiring intravenous (IV) antibiotics, antivirals, or antifungals within 14 days before study drug administration
Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection
Another serious or uncontrolled medical condition within 90 days before study drug administration such as acute myocardial infarction, angina, ventricular arrhythmias, hypertension, diabetes mellitus, or renal or hepatic insufficiency
Known hypersensitivity to benzamides
Women who are currently pregnant or breast-feeding
Patient currently is enrolled in (or completed within 28 days before study drug administration) another investigational drug study
Patient has any kind of medical, psychiatric, or behavioral disorder that places the patient at increased risk for study participation or compromises the ability of the patient to give written informed consent and/or to comply with study procedures and requirements

Name	Affiliation	Role
Samir Witta, MD	Rocky Mountain Cancer Centers	Principal Investigator
Kartik Konduri, MD	Texas Oncology - Sammons Cancer Center	Principal Investigator
Robert Raju, MD	Dayton Oncology	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
HOPE (Hematology Oncology Physicians & Extenders)		Tucson	Arizona		United States
Rocky Mountain Cancer Center

ID	Title	Description
FG000	Lead-in Phase: Erlotinib + Entinostat 5 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
FG001	Lead-in Phase: Erlotinib + Entinostat 10 mg

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

Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase

Safe recommended Phase 2 dose was determined based on dose-limiting toxicities (DLT) in Cycle 1. A DLT was defined as any of the following occurring in Cycle 1: Grade 3 or greater nonhematologic toxicity that was considered related to either entinostat or erlotinib or a Grade 4 hematologic toxicity lasting more than 7 days and/or resulting in a dose delay. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale was used where Grade 1=mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=life-threatening and 5=death. The dose that was found to be safe is reported.

Lead-in Safety Analysis Set included all participant who received at least one dose of study drug in the Lead-in Phase.

Posted

Number

milligrams (mg)

Cycle 1 of Lead-in Phase

ID	Title	Description
OG000	Lead-in Phase: Erlotinib + Entinostat	Participants received erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg or 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle for up to 6 cycles in the Open-label Lead-in Phase 1 dose-finding study to identify a safe dose of entinostat in combination with erlotinib for further evaluation.

Units	Counts
Participants	OG0009

Title

Denominators

Categories

Title	Measurements
	OG00010

Primary

4-Month Progression-free Survival (PFS) Rate in the Double-blind Phase

PFS rate at 4 months was defined as the percentage of participants who are progression-free at 4 months.

Double-blind Per-protocol Analysis Set included all randomized participants who met key eligibility criteria, received an adequate course of treatment and who had baseline and postbaseline tumor measurements.

Posted

Number

95% Confidence Interval

percentage of participants

Month 4

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants

Secondary

Objective Response Rate (ORR) in the Double-blind Phase

ORR was defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) as assessed by the investigator. CR=disappearance of all target lesions; disappearance of non-target lesions and normalization of tumor marker level. PR=At least a 30% decrease in the sum of the longest diameter of target lesions, taking at reference the baseline sum longest diameter.

Double-blind Full Analysis Set included all randomized participants.

Posted

Number

95% Confidence Interval

percentage of participants

Month 6

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Secondary

6-Month PFS Rate in the Double-blind Phase

PFS rate at 6 months is defined as the percentage of participants who are progression-free at 6 months.

Full Analysis Set included all randomized participants.

Posted

Number

95% Confidence Interval

percentage of participants

Month 6

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) by Severity in the Double-blind Phase

An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Worsening of a pre-existing medical condition was considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. A TEAE is an AE that starts after the administration of study drug.

A SAE is any AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth effect or other significant medical hazard.

TEAE severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=Life-threatening and 5=Death.

Safety Analysis Set included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

First dose of study drug to within 30 days past last dose (Up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Secondary

Number of Participants With Grade 3 or 4 Laboratory Variables in the Double-blind Phase

Laboratory tests included tests of Hematology and Chemistry. The individual laboratory values were graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=Life-threatening and 5=Death.

Safety Population included all participants who received at least one dose of study drug.

Posted

Count of Participants

Participants

Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Secondary

Vital Sign Values: Systolic Blood Pressure in the Double-blind Phase

Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available.

Posted

Mean

Standard Deviation

mm Hg

Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants	OG000

Secondary

Vital Sign Values: Diastolic Blood Pressure in the Double-blind Phase

Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available.

Posted

Mean

Standard Deviation

mm Hg

Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants	OG000

Secondary

Vital Sign Values: Heart Rate in the Double-blind Phase

Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available.

Posted

Mean

Standard Deviation

beats per minute (bpm)

Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants	OG000

Secondary

Vital Sign Values: Respiration Rate in the Double-blind Phase

Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available.

Posted

Mean

Standard Deviation

breaths per minute

Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants	OG000

Secondary

Vital Sign Values: Temperature in the Double-blind Phase

Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available.

Posted

Mean

Standard Deviation

degrees Celsius (C)

Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants	OG000

Secondary

Vital Sign Values: Weight in the Double-blind Phase

Safety Population included all participants who received at least one dose of study drug. Number analyzed is the number of participants with data available.

Posted

Mean

Standard Deviation

kilograms (kg)

Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)

ID	Title	Description
OG000	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
OG001	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.

Units	Counts
Participants	OG000

Secondary

Cmax: Maximum Plasma Concentration of Entinostat in the Lead-in Phase

Pharmacokinetic (PK) Population included all participants who had blood collected for PK parameters in the Lead-in Phase. Number analyzed is the number of participants with data available at the give timepoint.

Posted

Mean

Standard Deviation

ng/mL

Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose

ID	Title	Description
OG000	Lead-in Phase: Erlotinib + Entinostat 5 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
OG001	Lead-in Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.

Units	Counts
Participants

Secondary

Tmax: Time to Cmax of Entinostat in the Lead-in Phase

PK Population included all participants who had PK samples collected in the Lead-in Phase. Number analyzed is the number of participants with data available at the give time point.

Posted

Mean

Standard Deviation

hour

Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose

ID	Title	Description
OG000	Lead-in Phase: Erlotinib + Entinostat 5 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
OG001	Lead-in Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.

Units	Counts
Participants

Secondary

AUC(0-24): Area Under the Concentration-time Curve From Time 0 to 24 Hours in the Lead-in Phase

PK Population included all participants who had PK samples collected in the Lead-in Phase. Number analyzed is the number of participants with data available at the given timepoint

Posted

Mean

Standard Deviation

ng*hr/mL

Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose

ID	Title	Description
OG000	Lead-in Phase: Erlotinib + Entinostat 5 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
OG001	Lead-in Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.

Units	Counts
Participants

Secondary

AUC(0-last): Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration in the Lead-in Phase

PK Population included all participants who had PK samples collected during the Lead-in Phase. Number analyzed is the number of participants with data available at the given timepoint.

Posted

Mean

Standard Deviation

ng*hr/mL

Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose

ID	Title	Description
OG000	Lead-in Phase: Erlotinib + Entinostat 5 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
OG001	Lead-in Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Disease progression	General disorders	MedDRA 10.1	Systematic Assessment	EG0002 affected3 at risk EG0012 affected6 at risk EG00216 affected63 at risk EG0037 affected65 at risk EG0040 affected16 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0021 affected63 at risk EG003
Monoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Pain in extremity	General disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected63 at risk EG003
Pneumonia	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected63 at risk EG003
Anemia Group	Blood and lymphatic system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Asthenia	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Cardia disorder	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Chest pain	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Death	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Dehydration	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Diaphragmatic paralysis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hernia obstructive	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hypotension	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Peripheral artery aneurysm	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Syncope	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Thrombocytopenia Group	Blood and lymphatic system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Vena cava thrombosis	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Duodenal obstruction	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Genital rash	Reproductive system and breast disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected63 at risk EG003
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Metastases to spine	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Superior vena caval occlusion	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Hypertension	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Congestive cardiac failure	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Gastroenteritis	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Anemia	Blood and lymphatic system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0016 affected6 at risk EG00230 affected63 at risk EG00337 affected65 at risk EG0043 affected16 at risk
Fatigue	General disorders	MedDRA 10.1	Systematic Assessment	EG0003 affected3 at risk EG0015 affected6 at risk EG00232 affected63 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0013 affected6 at risk EG00216 affected63 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0002 affected3 at risk EG0013 affected6 at risk EG00235 affected63 at risk EG003
Asthenia	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected6 at risk EG0027 affected63 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected6 at risk EG0029 affected63 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected6 at risk EG0027 affected63 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected6 at risk EG00211 affected63 at risk EG003
Oedema peripheral	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected6 at risk EG0028 affected63 at risk EG003
Thrombocytopenia group	Blood and lymphatic system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected6 at risk EG0022 affected63 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0012 affected6 at risk EG0027 affected63 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0012 affected6 at risk EG0028 affected63 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0026 affected63 at risk EG003
Anemia group	Blood and lymphatic system disorders	MedDRA 10.1	Systematic Assessment	EG0002 affected3 at risk EG0011 affected6 at risk EG0027 affected63 at risk EG003
Anorexia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG00210 affected63 at risk EG003
Balance disorder	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Dizziness	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0026 affected63 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected6 at risk EG0024 affected63 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0024 affected63 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0011 affected6 at risk EG0027 affected63 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Monarthritis	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Neutropenia group	Blood and lymphatic system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0022 affected63 at risk EG003
Pyrexia	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0025 affected63 at risk EG003
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0020 affected63 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Chest pain	General disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0026 affected63 at risk EG003
Dry eye	Eye disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Flushing	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hair growth abnormal	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Headache	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0026 affected63 at risk EG003
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Photophobia	Eye disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0022 affected63 at risk EG003
Xerosis	General disorders	MedDRA 10.1	Systematic Assessment	EG0001 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Weight decreased	Investigations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG00211 affected63 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0025 affected63 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG00212 affected63 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected63 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0024 affected63 at risk EG003
Hypotension	Vascular disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0026 affected63 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected63 at risk EG003
Depression	Psychiatric disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected63 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0021 affected63 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected63 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0024 affected63 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0024 affected63 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0025 affected63 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0025 affected63 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0025 affected63 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0026 affected63 at risk EG003
Cellulitis	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Oedema	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Blood albumin decreased	Investigations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0023 affected63 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Eye discharge	Eye disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Eye infection	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Fungal infection	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0022 affected63 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hypersomnia	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Hypovolaemia	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Localised infection	Infections and infestations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Malaise	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Nasal dryness	Respiratory, thoracic and mediastinal disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Neuropathy	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Pain	General disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Peroneal nerve palsy	Nervous system disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Protein total decreased	Investigations	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Sensation of heaviness	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Vulvovaginal dryness	Reproductive system and breast disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0020 affected63 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0011 affected6 at risk EG0023 affected63 at risk EG003
Appetite disorder	Metabolism and nutrition disorders	MedDRA 10.1	Systematic Assessment	EG0000 affected3 at risk EG0010 affected6 at risk EG0024 affected63 at risk EG003

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D008175	Lung Neoplasms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	Lead-in Phase: Erlotinib + Entinostat 5 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
BG001	Lead-in Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
BG002	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
BG003	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
BG004	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lead-in Phase: Erlotinib + Entinostat 5 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.	2	3	3	3
EG001	Lead-in Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.	3	6	6	6
EG002	Double-blind Phase: Erlotinib + Placebo	Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.	29	63	63	63
EG003	Double-blind Phase: Erlotinib + Entinostat 10 mg	Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.	32	65	64	65
EG004	Crossover Phase: Erlotinib + Entinostat 10 mg	Participants in the Double-blind Phase Erlotinib + Placebo arm who experienced disease progression crossed over to receive open-label erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities.	5	16	14	16