Study of Erlotinib With or Without Investigational Drug (... | NCT01211483

Label	Type	Description	Intervention Names
Part A: U3-1287 (high dose) + Erlotinib	Experimental	U3-1287 (high dose) intravenously (IV) every three weeks (Q3W) + Erlotinib 150 mg/day orally (PO) until cancer gets worse, side effects become unacceptable or participant withdraws consent	Drug: U3-1287 Drug: Erlotinib
Part B: U3-1287 (low dose) + Erlotinib	Experimental	U3-1287 (low dose) IV Q3W + Erlotinib 150 mg/day PO until cancer gets worse, side effects become unacceptable or participant withdraws consent	Drug: U3-1287 Drug: Erlotinib
Part B: Placebo + Erlotinib	Placebo Comparator	Placebo matching U3-1287 IV Q3W + Erlotinib150 mg/day PO until cancer gets worse, side effects become unacceptable or participant withdraws consent	Drug: Erlotinib Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
U3-1287	Drug	Liquid 70 mg/mL for IV infusion at high dose or low dose	Part A: U3-1287 (high dose) + Erlotinib Part B: U3-1287 (low dose) + Erlotinib

Measure	Description	Time Frame
Progression-Free Survival Following U3-1287 (AMG 888) in Combination With Erlotinib	Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1).	Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months
Progression-Free Survival in Participants With High Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib	Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1). Heregulin (HRG) high is defined as delta cycle threshold value < 3.9.	Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months
Progression-Free Survival in Participants With Low Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib	Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1). Heregulin (HRG) low is defined as a delta cycle threshold value ≥ 3.9.	Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

Measure	Description	Time Frame
Overall Survival Following U3-1287 (AMG 888) in Combination With Erlotinib	Overall Survival (OS) was defined as the time from the randomization date to the date of death.	Time from the randomization date up to the date of death due to any cause, up to 3 years 2 months
Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

≥ 18 years of age.
Histologically or cytologically confirmed stage IIIB not amenable to surgery or curative intent or stage IV NSCLC.
Disease progression or recurrence following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months) documented by radiographic assessment.
Measurable disease by Response Evaluation Criteria for Solid Tumors v1.1 (RECIST v1.1).
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate bone marrow, renal, and hepatic function.
Prothrombin time and partial thromboplastin time ≤1.5 x upper limit of normal (ULN).
Availability of recent (before treatment start) or archival tumor specimens (Phase 2 participants only).
For female participants, must be postmenopausal, surgically sterile, or must use maximally effective birth control during the period of therapy, and must be willing to use effective contraception up to 6 months after the last dose of study drug and had a negative urine or serum pregnancy test before entry into the study if female participants were of childbearing potential.
For male participants, must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug dose
Written informed consent.

Exclusion Criteria:

Left ventricular ejection fraction (LVEF) < 45%.
Prior epidermal growth factor receptor (EGFR)-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy.
More than 2 prior chemotherapy regimens for NSCLC (Phase 2 participants only).
History of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.
History of corneal disease.
History of interstitial lung disease.
Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that were no longer symptomatic and required no treatment with steroids could be included in the study if they had recovered from the acute toxic effect of radiotherapy.
Uncontrolled hypertension (diastolic > 100 mmHg or systolic > 140 mmHg).
Clinically significant electrocardiogram changes that obscured the ability to assess the respiratory rate, pulse rate, QT, QTc, and QRS intervals.
Ascites or pleural effusion requiring chronic medical intervention.
Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure (New York Heart Association > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
Treatment with anticancer therapy, antibody based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study treatment or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment or treatment with small molecule tyrosine kinase inhibitors (TKIs) within 2 weeks before study drug treatment. Prior and concurrent use of hormone replacement therapy was permitted.
Therapeutic radiation or major surgery within 4 weeks before study treatment or palliative radiation therapy within 2 weeks before study drug treatment.
Participated in clinical drug trials within 4 weeks (2 weeks for small molecule TKIs) before study drug treatment. Current participation in other investigational procedures.
Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.
History of hypersensitivity to any of the study drugs or to any excipients.
Concurrent use of CYP3A4 inducers or inhibitors.
Any known pre-existing condition including substance abuse that could interfere with participant's participation in and completion of the protocol.

Name	Affiliation	Role
Global Clinical Leader	Daiichi Sankyo	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
		Glendale	Arizona		United States
TRM - Oncology Research Associates, PLLC, d/b/a Pinnacle Oncology Hematology

ID	Title	Description
FG000	Phase 1b: U31287 18 mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
FG001	Phase 2: U3-1287 18 mg/kg + Erlotinib

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

Progression-Free Survival Following U3-1287 (AMG 888) in Combination With Erlotinib

Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1).

Progression-free survival was assessed in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Median

95% Confidence Interval

months

Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib	Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.

Units	Counts
Participants	OG00070 OG00171 OG00271

Title

Denominators

Categories

Title	Measurements
	OG0001.4(1.3 to 2.7) OG0012.5(1.5 to 3.0) OG0021.6(1.4 to 2.6)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002						Hazard Ratio (HR)	0.978			2-Sided	95	0.674	1.420					Superiority
OG001 OG002

Primary

Progression-Free Survival in Participants With High Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib

Progression-free survival was assessed in participants with high heregulin-expressing tumors in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Median

95% Confidence Interval

months

Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib

Primary

Progression-Free Survival in Participants With Low Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib

Progression-free survival was assessed in participants with low heregulin-expressing tumors in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Median

95% Confidence Interval

months

Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib

Secondary

Overall Survival Following U3-1287 (AMG 888) in Combination With Erlotinib

Overall Survival (OS) was defined as the time from the randomization date to the date of death.

Overall survival was assessed in Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Median

95% Confidence Interval

months

Time from the randomization date up to the date of death due to any cause, up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib	Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.

Secondary

Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib

Objective response was defined as the best response of either complete response (CR) or partial response (PR). As per Response Evaluation Criteria in Solid Tumors Version 1.1, CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Objective response rate was assessed in participants with measurable disease in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Count of Participants

Participants

Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib	Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.

Secondary

Time to Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib

Time to objective response was defined as the time from the date of randomization to the date of the first documentation of objective response (complete response [CR] or partial response [PR]). As per Response Evaluation Criteria in Solid Tumors Version 1.1, CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Time to objective response was assessed among participants with objective response of CR or PR in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Median

95% Confidence Interval

weeks

Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib

Secondary

Duration of Stable Disease Following U3-1287 (AMG 888) in Combination With Erlotinib

Duration of stable disease (SD) was defined for participants whose best response is SD as the time from the date of randomization to the date of the first documentation of progressive disease. SD was defined as neither sufficient shrinkage to qualify for partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions).

Duration of stable disease (SD) was assessed among participants with best response of SD in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Median

95% Confidence Interval

weeks

For participants whose best response is SD as the time from date of first documentation of stable disease up to the date of first documentation of progressive disease, up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002

Secondary

Time to Disease Progression Following U3-1287 (AMG 888) in Combination With Erlotinib

Time to disease progression was defined as the time from the randomization date to the date of first objective documentation of disease progression. As per Response Evaluation Criteria in Solid Tumors Version 1.1, progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions.

Time to disease progression was assessed in the Full Analysis Set in Phase 2 of the study. Efficacy was not assessed in the Phase 1b portion of the study.

Posted

Median

95% Confidence Interval

weeks

Time from date of randomization up to the date of first objective documentation of disease progression, up to 3 years 2 months

ID	Title	Description
OG000	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib	Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.

Secondary

Pharmacokinetic Parameter of Cycle 3 Patritumab Area Under the Concentration-time Curve Over the Dosing Interval 0 to τ (AUC) Following U3-1287 (AMG 888) in Combination With Erlotinib

AUC was calculated from the concentration-time data at Cycle 3 using a noncompartmental analysis (NCA) method.

Area under the curve from 0 to tau was assessed in patients with available samples the Pharmacokinetic (PK) Analysis Set. The PK analysis sets for Phase 1b and Phase 2 were combined for the PK analyses.

Posted

Mean

Standard Deviation

hour*ug/mL

Cycle 1: predose, end of infusion (EOI), 3 hour (h) postdose; Cycle 2: predose; Cycle 3: predose, EOI, 3 h, 6h, 24 h, 72 h, 168 h, 336 h; Cycle 4, Cycle 5, Cycle 7, and Cycle 9: predose (each cycle is 21 days)

ID	Title	Description
OG000	Phase 1b and Phase 2: U31287 18 mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO). Phase 1b and Phase 2 PK analysis sets were combined for the PK analyses.
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.

Units	Counts

Secondary

Pharmacokinetic Parameter of Cycle 3 Patritumab Concentration End of Infusion (CEOI) and Minimum (Trough) Concentration (Cmin) Following U3-1287 (AMG 888) in Combination With Erlotinib

Concentration end of infusion (CEOI) was defined as the concentration within ± 5 minutes of the end of infusion. Cmin was defined as minimum (trough) observed concentration within ± 15% of the prescribed dosing interval. Preinfusion patritumab concentrations observed within 15% of nominal time after the start of the previous infusion (ie, 21 days ± 3.15 days) were considered trough concentrations

Concentration at end of infusion and minimum concentration were assessed in patients with available samples in the Pharmacokinetic Analysis Set. The PK analysis sets for Phase 1b and Phase 2 were combined for the PK analyses.

Posted

Mean

Standard Deviation

ug/mL

ID	Title	Description
OG000	Phase 1b and Phase 2: U31287 18 mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO). Phase 1b and Phase 2 PK analysis sets were combined for the PK analyses.
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.

Secondary

Erlotinib Concentrations at Cycle 3 Day 1 Following U3-1287 (AMG 888) in Combination With Erlotinib

Erlotinib concentrations were assessed in patients with available samples in the Pharmacokinetic Analysis Set. The PK analysis sets for Phase 1b and Phase 2 were combined for the PK analyses.

Posted

Mean

Standard Deviation

ng/mL

Cycle 3, Day 1: predose, 1 h, 2 h, 3 h, 6h, 24 h postdose (each cycle is 21 days)

ID	Title	Description
OG000	Phase 1b and Phase 2: U31287 18 mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO). Phase 1b and Phase 2 PK analysis sets were combined for the PK analyses.
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002	Phase 2: Placebo + Erlotinib	Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.

Units	Counts

Secondary

Pharmacokinetic Parameter of Erlotinib Trough (Cmin) Concentrations From Participants Receiving 150 mg Erlotinib Following U3-1287 (AMG 888) in Combination With Erlotinib

Trough concentrations (Cmin) was defined as minimum (trough) observed concentration within ± 15% of the prescribed dosing interval. Erlotinib Cmin was predose (or for participants with at least 2 prior doses, within 15% of nominal time after postdose) plasma erlotinib concentration.

Erlotinib concentrations were assessed in patients with available samples in the Pharmacokinetic Analysis Set. The PK analysis sets for Phase 1b and Phase 2 were combined for the PK analyses.

Posted

Mean

Standard Deviation

ng/mL

Cycle 1: predose, end of infusion (EOI), 3 hour (h) postdose; Cycle 2: predose; Cycle 3: predose, EOI, 3 h, 6h, 24 h, 72 h, 168 h, 336 h; Cycle 5, Cycle 7, and Cycle 9: predose (each cycle is 21 days)

ID	Title	Description
OG000	Phase 1b and Phase 2: U31287 18 mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO). Phase 1b and Phase 2 PK analysis sets were combined for the PK analyses.
OG001	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
OG002

Secondary

Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination With Erlotinib

A treatment-emergent adverse event (TEAE) was defined as an adverse event (AE) that: emerged during treatment, having been absent at pretreatment; or reemerged during treatment, having been present at baseline but stopped prior to treatment; or worsened in severity since treatment relative to the pretreatment state, when the AE was continuous.

TEAEs Occurring in ≥10% of Participants Following U3-1287 (AMG 888) in Combination with Erlotinib were analyzed in the Safety Analysis Set.

Posted

Count of Participants

Participants

From the date of signing the informed consent form up to 53 days after the last dose of patritumab/placebo or up to 30 days after the last dose of erlotinib if patritumab/placebo was discontinued earlier, up to 3 years 2 months

ID	Title	Description
OG000	Phase 1b: U3127 18mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG001	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
OG002	Phase 2: U3-1287 9 mg/kg + Erlotinib

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0013 affected70 at risk EG0022 affected71 at risk EG0032 affected71 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0015 affected70 at risk EG0020 affected71 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Bronchial haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0021 affected71 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Alveolitis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0014 affected70 at risk EG0025 affected71 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0013 affected70 at risk EG0022 affected71 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected70 at risk EG0021 affected71 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected70 at risk EG0020 affected71 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0021 affected71 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Intestinal obstruction	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Varices oesophageal	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Pneumonia	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0013 affected70 at risk EG0023 affected71 at risk EG003
Bronchitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Cellulitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Escherichia sepsis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Febrile infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Lung infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Sepsis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Skin infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
General physical health deterioration	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0014 affected70 at risk EG0022 affected71 at risk EG003
Asthenia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Fatigue	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Malaise	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Multi-organ failure	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Oedema peripheral	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Puncture site pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Cardio-respiratory arrest	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0021 affected71 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0021 affected71 at risk EG003
Cardiac disorder	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Cardiovascular insufficiency	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Cor pulmonale	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Ventricular fibrillation	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0021 affected71 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0021 affected71 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected70 at risk EG0020 affected71 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Blood bilirubin increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Blood creatinine increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Prothrombin time prolonged	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Weight decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Bile duct cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Anaemia of malignant disease	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Brain oedema	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0012 affected70 at risk EG0020 affected71 at risk EG003
Convulsion	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Grand mal convulsion	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Skeletal injury	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Circulatory collapse	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Panophthalmitis	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Depression	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Tumor associate fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0005 affected7 at risk EG00147 affected70 at risk EG00250 affected71 at risk EG00323 affected71 at risk
Nausea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0003 affected7 at risk EG00126 affected70 at risk EG00217 affected71 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG00118 affected70 at risk EG0027 affected71 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0012 affected70 at risk EG0021 affected71 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected70 at risk EG0022 affected71 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0007 affected7 at risk EG00135 affected70 at risk EG00238 affected71 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected7 at risk EG0015 affected70 at risk EG00212 affected71 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0012 affected70 at risk EG0022 affected71 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected70 at risk EG0022 affected71 at risk EG003
Pruritus generalized	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Fatigue	General disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected7 at risk EG00118 affected70 at risk EG00222 affected71 at risk EG003
Mucosal inflammation	General disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected70 at risk EG0025 affected71 at risk EG003
Asthenia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0017 affected70 at risk EG0024 affected71 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected7 at risk EG00118 affected70 at risk EG00217 affected71 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG00112 affected70 at risk EG00211 affected71 at risk EG003
Paronychia	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0018 affected70 at risk EG0025 affected71 at risk EG003
Weight decreased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG00110 affected70 at risk EG00216 affected71 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected70 at risk EG0022 affected71 at risk EG003
Conjunctivitis	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Vision blurred	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0017 affected70 at risk EG0026 affected71 at risk EG003
Ventricular arrhythmia	Cardiac disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Dry eye	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Ocular hyperaemia	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0019 affected70 at risk EG0029 affected71 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0019 affected70 at risk EG00210 affected71 at risk EG003
Faecal incontinence	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Glossitis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Lip dry	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Oral disorder	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Gait disturbance	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Oedema peripheral	General disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0019 affected70 at risk EG0029 affected71 at risk EG003
Temperature intolerance	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Candidiasis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0003 affected7 at risk EG0013 affected70 at risk EG0026 affected71 at risk EG003
Device related infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected70 at risk EG0020 affected71 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected70 at risk EG0026 affected71 at risk EG003
Tinea cruris	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0015 affected70 at risk EG0024 affected71 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0010 affected70 at risk EG0022 affected71 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected70 at risk EG0022 affected71 at risk EG003
Sunburn	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Blood creatinine increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0022 affected71 at risk EG003
Blood pressure increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Blood urea increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0003 affected7 at risk EG0010 affected70 at risk EG0024 affected71 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0014 affected70 at risk EG0021 affected71 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0016 affected70 at risk EG0023 affected71 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected70 at risk EG0021 affected71 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected70 at risk EG0024 affected71 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Ataxia	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Dizziness	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Headache	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0012 affected70 at risk EG0023 affected71 at risk EG003
Hyperaesthesia	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Peroneal nerve palsy	Pregnancy, puerperium and perinatal conditions	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Presyncope	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Confusional state	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Depression	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0013 affected70 at risk EG0023 affected71 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0012 affected70 at risk EG0024 affected71 at risk EG003
Libido decreased	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0012 affected70 at risk EG0020 affected71 at risk EG003
Incontinence	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Nocturia	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Urinary hesitation	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0015 affected70 at risk EG00211 affected71 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0016 affected70 at risk EG0026 affected71 at risk EG003
Hiccups	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Postnasal drip	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0012 affected70 at risk EG0020 affected71 at risk EG003
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0021 affected71 at risk EG003
Ecchymosis	Social circumstances	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Onychoclasis	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0021 affected71 at risk EG003
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected7 at risk EG0011 affected70 at risk EG0020 affected71 at risk EG003
Pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected7 at risk EG0010 affected70 at risk EG0020 affected71 at risk EG003
Pyrexia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected7 at risk EG0018 affected70 at risk EG0026 affected71 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	Phase 1b: U3127 18mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
BG001	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).
BG002	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.
BG003	Phase 2: Placebo + Erlotinib	Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.
BG004	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	Phase 1b: U31287 18mg/kg + Erlotinib	Participants who received U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	6	7	3	7	7	7
EG001	Phase 2: U3-1287 18 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 18 mg/kg intravenously (IV) every three weeks (Q3W) and Erlotinib 150 mg/day orally (PO).	64	70	35	70	69	70
EG002	Phase 2: U3-1287 9 mg/kg + Erlotinib	Participants who were randomized to receive U3-1287 9 mg/kg IV Q3W and Erlotinib 150 mg/day PO.	53	71	24	71	70	71
EG003	Phase 2: Placebo + Erlotinib	Participants who were randomized to receive placebo matching U3-1287 IV Q3W and Erlotinib150 mg/day PO.	53	71	24	71	69	71