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Clinical Trial Results:
A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Subjects with Select Advanced Malignancies

Summary
EudraCT number	2016-000323-43
Trial protocol	GB NL
Global end of trial date	17 Mar 2020

Results information
Results version number	v2(current)
This version publication date	26 May 2021
First version publication date	20 Mar 2021
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

D6020C00001

ISRCTN number

US NCT number

NCT02118337

WHO universal trial number (UTN)

Sponsor organisation name

MedImmune, LLC

Sponsor organisation address

One MedImmune Way, Gaithersburg, United States, 20878

Public contact

Farzana Walcott, MedImmune, LLC, +1 3013983063, information.center@astrazeneca.com

Scientific contact

Farzana Walcott, MedImmune, LLC, +1 3013983063, information.center@astrazeneca.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

30 Oct 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Mar 2020

Was the trial ended prematurely?

Main objective of the trial

The main objectives of the study are as below: 1. For dose-escalation phase: To determine safety profile of of MEDI0680 in combination with durvalumab in participants with select advanced malignancies. 2. For dose-expansion: To evaluate the antitumor activity of MEDI0680 in combination with durvalumab versus nivolumab monotherapy in immunotherapy naïve participants with advanced or metastatic clear cell renal cell carcinoma (ccRCC) as based on investigator assessed response using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Protection of trial subjects

The conduct of this clinical study met all local and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and are consistent with International Conference on Harmonization guideline: Good Clinical Practice, and applicable regulatory requirements. Participants signed an informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 May 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 7

Country: Number of subjects enrolled

Canada: 5

Country: Number of subjects enrolled

France: 8

Country: Number of subjects enrolled

Netherlands: 8

Country: Number of subjects enrolled

United Kingdom: 3

Country: Number of subjects enrolled

United States: 66

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study is conducted in Australia, Canada, France, Netherlands, United Kingdom, and the United States.

Screening details

Of the 130 participants screened, 97 participants were enrolled and were treated in this study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

MEDI0680 0.1 mg/kg + Durvalumab 3 mg

Arm description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Intravenous (IV) infusion of MEDI0680 0.1 mg/kg Q2W for up to 12 months.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of durvalumab 3 mg Q2W for up to 12 months.

MEDI0680 0.1 mg/kg + Durvalumab 10 mg

Arm description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of MEDI0680 0.1 mg/kg Q2W for up to 12 months.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of durvalumab 10 mg Q2W for up to 12 months.

MEDI0680 0.5 mg/kg + Durvalumab 10 mg

Arm description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of MEDI0680 0.5 mg/kg Q2W for up to 12 months.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of durvalumab 10 mg Q2W for up to 12 months.

MEDI0680 2.5 mg/kg + Durvalumab 10 mg

Arm description

Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of MEDI0680 2.5 mg/kg Q2W for up to 12 months.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of durvalumab 10 mg Q2W for up to 12 months.

MEDI0680 10 mg/kg + Durvalumab 10 mg

Arm description

Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of MEDI0680 10 mg/kg Q2W for up to 12 months.

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of durvalumab 10 mg Q2W for up to 12 months.

MEDI0680 20 mg/kg + Durvalumab 10 mg

Arm description

Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of MEDI0680 20 mg/kg Q2W for up to 12 months

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of durvalumab 10 mg Q2W for up to 12 months.

MEDI0680 20 mg/kg

Arm description

Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

MEDI0680 20 mg/kg + Durvalumab 750 mg

Arm description

Participants in dose-expansion phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

MEDI0680

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Investigational medicinal product name

Durvalumab

Investigational medicinal product code

MEDI4736

Other name

Pharmaceutical forms

Powder and solvent for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of durvalumab 750 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Nivolumab 240 mg

Arm description

Participants in dose-expansion phase received IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

IV infusion of nivolumab 240 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Number of subjects in period 1	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Started	4	5	3	3	9	6	4	42	21
Completed	0	0	0	0	0	0	0	0	0
Not completed	4	5	3	3	9	6	4	42	21
Consent withdrawn by subject	1	3	2	1	2	2	1	4	2
Death	2	2	1	2	5	1	2	9	4
Unspecified	1	-	-	-	2	3	1	28	15
Lost to follow-up	-	-	-	-	-	-	-	1	-

Baseline characteristics

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Reporting group title

MEDI0680 0.1 mg/kg + Durvalumab 3 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.

Reporting group title

MEDI0680 0.1 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 0.5 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 2.5 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 10 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 20 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 20 mg/kg

Reporting group description

Reporting group title

MEDI0680 20 mg/kg + Durvalumab 750 mg

Reporting group description

Reporting group title

Nivolumab 240 mg

Reporting group description

Reporting group values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg	Total
Number of subjects	4	5	3	3	9	6	4	42	21	97
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	2	2	2	2	7	1	2	21	17	56
From 65-84 years	2	3	1	1	1	5	2	21	4	40
85 years and over	0	0	0	0	1	0	0	0	0	1
Age Continuous
Units: years
arithmetic mean (standard deviation)	60.5 ( 12.6 )	67.4 ( 8.4 )	52.3 ( 17.9 )	62.3 ( 11.6 )	62.1 ( 11.0 )	69.5 ( 9.9 )	64.8 ( 14.2 )	61.0 ( 9.8 )	59.1 ( 10.5 )	-
Sex: Female, Male
Units: Participants
Female	1	3	1	1	5	2	1	9	6	29
Male	3	2	2	2	4	4	3	33	15	68
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	1	0	0	1
Asian	0	1	0	0	0	0	0	1	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	1	0	0	0	0	1
Black or African American	0	0	0	0	0	0	0	0	3	3
White	4	4	3	2	8	6	3	34	16	80
More than one race	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	1	0	0	0	7	2	10
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	0	1	0	2	0	0	1	1	6
Not Hispanic or Latino	3	5	2	2	7	6	4	40	20	89
Unknown or Not Reported	0	0	0	1	0	0	0	1	0	2

End points

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Reporting group title

MEDI0680 0.1 mg/kg + Durvalumab 3 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.

Reporting group title

MEDI0680 0.1 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 0.5 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 2.5 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 10 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 20 mg/kg + Durvalumab 10 mg

Reporting group description

Participants in dose-escalation phase received IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Reporting group title

MEDI0680 20 mg/kg

Reporting group description

Reporting group title

MEDI0680 20 mg/kg + Durvalumab 750 mg

Reporting group description

Reporting group title

Nivolumab 240 mg

Reporting group description

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase

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End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase ^[1] ^[2]

End point description

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Primary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Participants
Any TEAE	4	5	3	3	9	6
Any TESAE	1	1	1	2	6	0

No statistical analyses for this end point

Primary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase

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End point title

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase ^[3] ^[4]

End point description

Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Primary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Participants
Anaemia	0	0	1	1	3	0
Iron deficiency anaemia	0	0	0	0	1	0
Leukocytosis	1	0	0	0	0	0
Lymphopenia	0	0	0	0	1	0
Activated partial thromboplastin time prolonged	0	0	0	0	0	1
Blood fibrinogen decreased	1	0	0	0	0	1
International normalized ratio	0	0	0	0	0	1
Lymphocyte count decreased	0	0	0	0	0	1
Prothrombin time prolonged	0	0	0	0	0	1
White blood cell count decreased	0	0	0	0	0	1
Alanine aminotransferase increased	0	0	0	0	1	0
Amylase increased	0	0	0	0	1	1
Aspartate aminotransferase increased	0	0	0	0	2	0
Blood alkaline phosphatase increased	1	0	1	0	1	0
Blood creatinine increased	0	0	0	0	2	1
Blood phosphorus decreased	1	0	0	0	0	0
Blood urea increased	0	0	0	0	1	0
Gamma glutamyltransferase increased	0	0	0	0	1	0
Lipase increased	1	0	1	0	1	0
Hypercalcaemia	0	0	0	0	1	1
Hyperglycaemia	0	0	0	0	1	0
Hyperkalaemia	0	0	0	0	1	0
Hypermagnesaemia	0	0	1	0	0	0
Hyperuricaemia	1	0	0	0	1	0
Hypoalbuminaemia	0	0	0	0	1	0
Hypokalaemia	0	0	0	0	2	0
Hypomagnesaemia	0	0	0	0	2	0
Hyponatraemia	0	0	0	0	2	1
proteinuria	0	0	0	0	1	0

No statistical analyses for this end point

Primary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase

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End point title

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase ^[5] ^[6]

End point description

Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Primary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Participants
Atrial fibrillation	0	0	0	0	1	0
Palpitations	1	0	0	0	0	0
Sinus tachycardia	0	0	0	0	1	0
Tachycardia	0	0	0	0	0	1
Pyrexia	0	0	2	0	3	1
Weight decreased	0	0	0	0	1	1
Hypertension	1	0	0	0	1	1

No statistical analyses for this end point

Primary: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase

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End point title

Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase ^[7] ^[8]

End point description

Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Primary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for the end points.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Participants
Palpitations	1	0	0	0	0	0
Atrial fibrillation	0	0	0	0	1	0
Sinus tachycardia	0	0	0	0	1	0
Pericardial effusion	0	0	0	0	1	0
Tachycardia	0	0	0	0	0	1

No statistical analyses for this end point

Primary: Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose-expansion Phase

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End point title

Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose-expansion Phase ^[9]

End point description

The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. As-treated population was analysed for this end point.

End point type

Primary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Percentage of participants
number (confidence interval 95%)	0 (0 to 60.2)	16.7 (7.0 to 31.4)	23.8 (8.2 to 47.2)

Statistical Analysis 1

Comparison groups

MEDI0680 20 mg/kg v Nivolumab 240 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.5494

Method

Fisher exact

Parameter type

Rate difference

Point estimate

-23.8

Confidence interval

level

95%

sides

2-sided

lower limit

-72.8

upper limit

31.1

Statistical Analysis 2

Comparison groups

MEDI0680 20 mg/kg + Durvalumab 750 mg v Nivolumab 240 mg

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

P-value

= 0.513

Method

Fisher exact

Parameter type

Rate difference

Point estimate

-7.1

Confidence interval

level

95%

sides

2-sided

lower limit

-33.6

upper limit

Secondary: Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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End point title

Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase ^[10]

End point description

The BOR includes CR, PR, stable disease (SD), progressive disease (PD), and non-evaluable (NE) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment. As-treated population was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Participants
CR	0	2	0
PR	0	5	5
SD	3	17	8
PD	1	17	6
NE	0	1	2

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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End point title

Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase ^[11]

End point description

The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The DCR at >= 8 weeks and >=24 weeks are reported. As-treated population was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Percentage of participants
number (confidence interval 95%)
DCR at >=8 weeks	75.0 (19.4 to 99.4)	57.1 (41.0 to 72.3)	61.9 (38.4 to 81.9)
DCR at >=24 weeks	50.0 (6.8 to 93.2)	38.1 (23.6 to 54.4)	38.1 (18.1 to 61.6)

No statistical analyses for this end point

Secondary: Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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End point title

Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase ^[12]

End point description

The TTR is defined as the time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. The TTR was analysed for participants from As-treated population who achieved OR.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	0 ^[13]	7	5
Units: Months
median (confidence interval 95%)	( to )	1.8 (1.7 to 9.1)	1.8 (1.6 to 7.3)

Notes
[13] - No participant had achieved OR.

No statistical analyses for this end point

Secondary: Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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End point title

Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase ^[14]

End point description

The DoR is defined as duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The confirmed CR or confirmed PR means 2 CRs (disappearance of all target and non-target lesions and no new lesions) or 2 PRs ((>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between; and PD means at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The DoR was estimated using Kaplan-Meier method. The arbitrary numbers 99.999 and 99999 signified the data for median and upper limit of confidence interval could not be derived due to insufficient events being observed at the time of the analysis. The DoR was analysed for participants from As-treated population who achieved OR.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	0 ^[15]	7	5
Units: Months
median (confidence interval 95%)	( to )	99.999 (12.9 to 99999)	99.999 (4.4 to 99999)

Notes
[15] - No participant had achieved OR in this arm.

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

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End point title

Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase ^[16]

End point description

The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. The PFS was estimated using Kaplan-Meier method. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Months
median (confidence interval 95%)	5.5 (2.2 to 7.4)	3.6 (2.0 to 5.5)	3.6 (1.9 to 13.0)

No statistical analyses for this end point

Secondary: Overall Survival in Dose-expansion Phase

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End point title

Overall Survival in Dose-expansion Phase ^[17]

End point description

The OS is defined as the time from the start of study treatment until death due to any cause. The OS was estimated using Kaplan-Meier method. The arbitrary numbers 99.999, 0.9999, and 99999 signified the data for median, and lower and upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Months
median (confidence interval 95%)	19.9 (7.0 to 19.9)	99.999 (0.9999 to 99999)	99.999 (12.0 to 99999)

No statistical analyses for this end point

Secondary: BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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End point title

BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase ^[18]

End point description

The BOR includes CR, PR, SD, PD, and NE per Modified RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new nontarget lesion. The PD is defined at least 20% decrease in the sum of diameters of target lesions (compared to baseline) and/or new lesion. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The NE is defined as either when no or only a subset of lesion measurements are made at an assessment. As-treated population was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Participants
CR	0	0	0	0	1	0
PR	2	0	1	0	3	4
SD	1	1	0	1	2	1
PD	1	3	2	1	2	1
NE	0	1	0	1	1	0

No statistical analyses for this end point

Secondary: ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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End point title

ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase ^[19]

End point description

The ORR is defined as best overall response of confirmed CR or confirmed PR based on modified RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. As-treated population was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Percentage of participants
number (confidence interval 95%)	50.0 (6.8 to 93.2)	0 (0 to 52.2)	33.3 (0.8 to 90.6)	0 (0 to 70.8)	44.4 (13.7 to 78.8)	66.7 (22.3 to 95.7)

No statistical analyses for this end point

Secondary: DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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End point title

DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase ^[20]

End point description

The DCR is defined as a BOR of confirmed CR, confirmed PR, or SD based on modified RECIST v1.1. A confirmed CR is defined as two CRs (disappearance of all target and non-target lesions and no new lesions) that were separated by at least 4 weeks with no evidence of progression in-between. A confirmed PR is defined as two PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. The DCR at >= 8 weeks and >=24 weeks are reported. As-treated population was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Percentage of participants
number (confidence interval 95%)
DCR at >= 8 weeks	75.0 (19.4 to 99.4)	20.0 (0.5 to 71.6)	33.3 (0.8 to 90.6)	33.3 (0.8 to 90.6)	66.7 (29.9 to 92.5)	83.3 (35.9 to 99.6)
DCR at >= 24 weeks	50.0 (6.8 to 93.2)	0 (0 to 52.2)	33.3 (0.8 to 90.6)	0 (0 to 70.8)	44.4 (13.7 to 78.8)	83.3 (35.9 to 99.6)

No statistical analyses for this end point

Secondary: TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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End point title

TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase ^[21]

End point description

The TTR is defined as time from the first dose of treatment until the first documentation of a subsequently confirmed OR (confirmed CR or confirmed PR) based on modified RECIST v1.1. Confirmed CR or confirmed PR are defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) or 2 PRs (>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The TTR was estimated using Kaplan-Meier method. As-treated population was analysed for this end point. The arbitrary numbers 0.9999 and 99999 signified the data for lower and upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. The TTR was analysed for participants from As-treated population who achieved OR.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	2	0 ^[22]	1	0 ^[23]	4	4
Units: Months
median (confidence interval 95%)	2.6 (1.6 to 3.5)	( to )	3.4 (0.9999 to 99999)	( to )	3.5 (1.6 to 3.5)	3.2 (1.7 to 10.8)

Notes
[22] - No participant had achieved OR.
[23] - No participant had achieved OR.

No statistical analyses for this end point

Secondary: DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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End point title

DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase ^[24]

End point description

The DoR is defined as duration from the first documentation of OR (confirmed CR or confirmed PR) to the first documented disease progression based on RECIST v1.1 or death due to any cause, whichever occurred first. Confirmed CR or confirmed PR are defined as 2 CRs (disappearance of all target and non-target lesions and no new lesions) or 2 PRs ((>= 30% decrease in the sum of diameters of target lesions compared to baseline and no new non-target lesion) that were separated by at least 4 weeks with no evidence of progression in-between. The DoR was estimated using Kaplan-Meier method. The arbitrary numbers 99.999, 0.9999, and 99999 signified data for median, and lower and upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. The DoR was analysed for participants from As-treated population who achieved OR.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

Notes
[24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	2	0 ^[25]	1	0 ^[26]	4	4
Units: Months
median (confidence interval 95%)	16.8 (0.9999 to 99999)	( to )	99.999 (0.9999 to 99999)	( to )	7.4 (5.6 to 99999)	99.999 (5.6 to 99999)

Notes
[25] - No participant had achieved OR.
[26] - No participant had achieved OR.

No statistical analyses for this end point

Secondary: PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

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End point title

PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase ^[27]

End point description

The PFS is defined as the time from the start of study treatment until the first documentation of disease progression based on modified RECIST v1.1 or death due to any cause, whichever occurred first. The arbitrary number 99999 signified the data for upper limit of confidence interval could not be derived due to insufficient number of events being observed at the time of the analysis. The PFS was estimated using Kaplan-Meier method. As-treated population was analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

Notes
[27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Months
median (confidence interval 95%)	20.2 (1.6 to 20.2)	1.7 (1.6 to 3.5)	1.6 (1.6 to 99999)	1.8 (1.5 to 3.4)	7.0 (1.6 to 99999)	23.4 (1.8 to 99999)

No statistical analyses for this end point

Secondary: OS in Dose-escalation Phase

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End point title

OS in Dose-escalation Phase ^[28]

End point description

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg
Number of subjects analysed	4	5	3	3	9	6
Units: Months
median (confidence interval 95%)	16.3 (3.6 to 99999)	99.999 (4.2 to 99999)	14.7 (0.9999 to 99999)	7.9 (1.5 to 7.9)	12.8 (3.1 to 99999)	99.999 (29.6 to 99999)

No statistical analyses for this end point

Secondary: Number of Participants With TEAEs and TESAEs in Dose-expansion Phase

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End point title

Number of Participants With TEAEs and TESAEs in Dose-expansion Phase ^[29]

End point description

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Participants
Any TEAE	4	42	20
Any TESAE	3	22	13

No statistical analyses for this end point

Secondary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase

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End point title

Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase ^[30]

End point description

Number of participants in dose-expansion phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Participants
Anaemia	1	6	5
Neutropenia	0	1	0
Blood iron decreased	0	0	1
Lymphocyte count decreased	0	0	1
Neutrophil count decreased	1	1	0
Platelet count decreased	0	0	1
Platelet count increased	0	0	1
Prothrombin time prolonged	0	0	1
White blood cell count increased	0	0	1
Alanine aminotransferase increased	1	1	3
Amylase decreased	0	0	1
Amylase increased	1	3	3
Aspartate aminotransferase increased	1	2	3
Blood alkaline phosphatase increased	0	0	1
Blood bilirubin increased	0	0	1
Blood creatine increased	1	1	0
Blood creatine phosphokinase increased	0	1	0
Blood creatinine increased	1	4	3
Blood glucose increased	0	0	1
Blood triglycerides increased	0	1	1
C-reactive protein increased	0	1	1
Lipase increased	1	4	2
Transaminases increased	0	1	0
Hypercalcaemia	0	6	2
Hyperglycaemia	0	1	0
Hyperkalaemia	0	2	2
Hypertriglyceridaemia	0	1	0
Hypoalbuminaemia	0	2	0
Hypocalcaemia	0	1	0
Hypoglycaemia	0	1	0
Hypokalaemia	0	5	2
Hypomagnesaemia	0	4	2
Hyponatraemia	1	3	1
Hypophosphataemia	0	1	3
Urine abnormality	0	1	0
Blood thyroid stimulating hormone increased	0	2	2
Blood urine present	0	0	1

No statistical analyses for this end point

Secondary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase

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End point title

Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase ^[31]

End point description

Number of participants in dose-expansion phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Participants
Atrial fibrillation	0	2	1
Tachycardia	0	1	0
Pyrexia	2	9	2
Weight decreased	0	5	0
Weight increased	0	3	0
Hypoxia	0	1	1
Hypertension	1	5	0
Hypotension	1	2	1

No statistical analyses for this end point

Secondary: Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase

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End point title

Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase ^[32]

End point description

Number of participants in dose-expansion phase with abnormal ECG parameters reported as TEAEs are reported. As-treated population (participants who received any study drug [MEDI0680, durvalumab, or nivolumab] and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Participants
Angina pectoris	1	1	0
Tachycardia	0	1	0
Atrial fibrillation	0	2	1
Cardiac failure congestive	0	0	1

No statistical analyses for this end point

Secondary: Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases

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End point title

Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases ^[33]

End point description

Serum concentration of MEDI0680 were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration. Participants from As-treated population who received MEDI0680, grouped according to actual treatment received, and had quantifiable and calculable serum samples at the specified time points were analysed for this end point. The arbitrary number 9999.9 signified the sample was not quantifiable and therefore, not calculable. The arbitrary number 0.0009 signified no data as no participants were analysed for the specified time points. Here, 'n' denotes the number of participants analysed at the specified time points.

End point type

Secondary

End point timeframe

Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg
Number of subjects analysed	4	5	3	3	9	6	4	40
Units: μg/mL
geometric mean (geometric coefficient of variation)
Cmin at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 6, 4, 40)	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )
Cmax at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 4, 4, 38)	4.330 ( 26.18 )	3.877 ( 54.68 )	16.36 ( 26.46 )	69.28 ( 24.76 )	272.4 ( 24.62 )	529.9 ( 29.84 )	668.8 ( 21.04 )	135.9 ( 4007 )
Cmin at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 5, 0, 0)	1.143 ( 22.70 )	0.9937 ( 35.93 )	4.428 ( 62.38 )	18.67 ( 12.88 )	46.87 ( 559.4 )	205.8 ( 24.56 )	0.0009 ( 0.0009 )	0.0009 ( 0.0009 )
Cmax at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 5, 0, 0)	5.420 ( 21.61 )	3.835 ( 25.30 )	20.52 ( 26.26 )	87.78 ( 20.69 )	348.1 ( 27.78 )	716.8 ( 26.72 )	0.0009 ( 0.0009 )	0.0009 ( 0.0009 )
Cmin at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 4, 36)	1.645 ( 49.08 )	1.361 ( 38.07 )	7.879 ( 52.74 )	31.81 ( 4.480 )	155.7 ( 24.20 )	378.0 ( 17.95 )	308.6 ( 30.45 )	253.9 ( 52.11 )
Cmax at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 4, 34)	3.515 ( 145.9 )	3.688 ( 80.17 )	17.28 ( 56.32 )	92.07 ( 17.72 )	440.7 ( 28.18 )	860.8 ( 13.82 )	936.1 ( 24.91 )	586.6 ( 63.42 )

No statistical analyses for this end point

Secondary: Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases

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End point title

Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases ^[34]

End point description

Serum concentration of durvalumab were assessed using parameters Cmin (pre-dose) and Cmax (end of infusion), where Cmin was trough concentration and Cmax was peak concentration. Participants from As-treated population who received durvalumab, grouped according to actual treatment received, and had quantifiable and calculable serum samples at the specified time points were analysed for this end point. The arbitrary number 9999.9 signified the sample was not quantifiable and therefore, not calculable. The arbitrary number 0.0009 signified no data as no participants were analysed for the specified time points. Here, 'n' denotes the number of participants analysed at the specified time points.

End point type

Secondary

End point timeframe

Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1

Notes
[34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 750 mg
Number of subjects analysed	4	5	3	3	9	6	41
Units: μg/mL
geometric mean (geometric coefficient of variation)
Cmin at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 6, 38)	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )	9999.9 ( 9999.9 )
Cmax at Cycle1 Day1 (n = 4, 5, 3, 3, 9, 6, 41)	65.47 ( 10.02 )	216.1 ( 25.14 )	213.8 ( 9.943 )	188.0 ( 17.82 )	248.0 ( 27.20 )	253.9 ( 11.35 )	186.9 ( 33.42 )
Cmin at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 6, 0)	19.62 ( 16.49 )	63.02 ( 7.836 )	49.04 ( 80.97 )	86.10 ( 69.76 )	79.59 ( 63.46 )	70.31 ( 22.00 )	0.0009 ( 0.0009 )
Cmax at Cycle1 Day15 (n = 4, 3, 3, 3, 8, 6, 0)	95.14 ( 12.79 )	245.8 ( 13.45 )	241.1 ( 30.90 )	225.0 ( 9.213 )	292.7 ( 33.84 )	321.8 ( 23.05 )	0.0009 ( 0.0009 )
Cmin at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 27)	23.83 ( 14.35 )	83.76 ( 34.29 )	89.20 ( 56.00 )	136.3 ( 45.72 )	124.8 ( 55.78 )	142.5 ( 50.52 )	78.41 ( 55.62 )
Cmax at Cycle2 Day1 (n = 4, 4, 3, 3, 7, 6, 32)	84.43 ( 17.13 )	280.9 ( 12.48 )	297.5 ( 42.41 )	267.0 ( 25.97 )	370.9 ( 42.57 )	342.3 ( 18.08 )	258.1 ( 28.36 )

No statistical analyses for this end point

Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases

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End point title

Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases ^[35]

End point description

Number of participants with positive ADAs to MEDI0680 are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive). As-treated population (participants who received MEDI0680 and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)

Notes
[35] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg
Number of subjects analysed	4	5	3	3	8	6	4	39
Units: Participants
ADA positive post-baseline	2	0	2	0	0	0	0	2
Persistent Positive	2	0	2	0	0	0	0	0
Transient Positive	0	0	0	0	0	0	0	2

No statistical analyses for this end point

Secondary: Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases

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End point title

Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases ^[36]

End point description

Number of participants with positive ADA to durvalumab are reported. Persistent positive is defined as positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >=2 post-baseline assessments (with <16 weeks between first and last positive). As-treated population (participants who received durvalumab and grouped according to actual treatment received) was analysed for this end point.

End point type

Secondary

End point timeframe

Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 0.1 mg/kg + Durvalumab 3 mg	MEDI0680 0.1 mg/kg + Durvalumab 10 mg	MEDI0680 0.5 mg/kg + Durvalumab 10 mg	MEDI0680 2.5 mg/kg + Durvalumab 10 mg	MEDI0680 10 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 10 mg	MEDI0680 20 mg/kg + Durvalumab 750 mg
Number of subjects analysed	4	5	3	3	8	6	39
Units: Participants
ADA positive post-baseline	1	0	0	0	0	0	2
Persistent Positive	1	0	0	0	0	0	2
Transient Positive	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase

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End point title

ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase ^[37]

End point description

ORR for participants with PD-L1 status positive and negative are reported. The ORR is defined as best overall response of confirmed CR or confirmed PR based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between. Participants from As-treated population with PD-L1 positive (> 1% tumor cell membrane or > 1% immune cell staining) and PD-L1 negative (<= 1% tumor cell membrane and <= 1% immune cell staining) were analysed for this end point.

End point type

Secondary

End point timeframe

From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	MEDI0680 20 mg/kg	MEDI0680 20 mg/kg + Durvalumab 750 mg	Nivolumab 240 mg
Number of subjects analysed	4	42	21
Units: Percentage of Participants
number (confidence interval 95%)
Participants with PD-L1 positive	0 (0 to 97.5)	40.0 (5.3 to 85.3)	37.5 (8.5 to 75.5)
Participants with PD-L1 negative	0 (0 to 70.8)	13.5 (4.5 to 28.8)	15.4 (1.9 to 45.4)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

MEDI0680 0.1 mg/kg Q2W + Durva 3 mg/kg Q2W

Reporting group description

Reporting group title

MEDI0680 0.1 mg/kg Q2W + Durva 10 mg/kg Q2W

Reporting group description

Reporting group title

MEDI0680 0.5 mg/kg Q2W + Durva 10 mg/kg Q2W

Reporting group description

Reporting group title

MEDI0680 2.5 mg/kg Q2W + Durva 10 mg/kg Q2W

Reporting group description

Reporting group title

MEDI0680 10 mg/kg Q2W + Durva 10 mg/kg Q2W

Reporting group description

Reporting group title

MEDI0680 20 mg/kg Q2W + Durva 10 mg/kg Q2W

Reporting group description

Reporting group title

MEDI0680 20 mg/kg Q2W

Reporting group description

Reporting group title

MEDI0680 20 mg/kg Q2W + Durva 750 mg Q2W

Reporting group description

Reporting group title

Nivolumab 240mg Q2W

Reporting group description

Serious adverse events	MEDI0680 0.1 mg/kg Q2W + Durva 3 mg/kg Q2W	MEDI0680 0.1 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 0.5 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 2.5 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 10 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg Q2W + Durva 750 mg Q2W	Nivolumab 240mg Q2W
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	6 / 9 (66.67%)	0 / 6 (0.00%)	3 / 4 (75.00%)	22 / 42 (52.38%)	13 / 21 (61.90%)
number of deaths (all causes)	2	2	1	2	5	1	2	9	4
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to central nervous system
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Chills
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	4 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mental status changes
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Hip fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Aphasia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrospinal fluid leakage
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Encephalitis autoimmune
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intracranial mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Eye pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	2 / 21 (9.52%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis microscopic
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated enterocolitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated pancreatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatocellular injury
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Diabetic foot
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rash papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia of malignancy
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperthyroidism
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypothyroidism
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	3 / 21 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myalgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal cord infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	MEDI0680 0.1 mg/kg Q2W + Durva 3 mg/kg Q2W	MEDI0680 0.1 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 0.5 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 2.5 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 10 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W + Durva 10 mg/kg Q2W	MEDI0680 20 mg/kg Q2W	MEDI0680 20 mg/kg Q2W + Durva 750 mg Q2W	Nivolumab 240mg Q2W
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	5 / 5 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	9 / 9 (100.00%)	6 / 6 (100.00%)	4 / 4 (100.00%)	41 / 42 (97.62%)	20 / 21 (95.24%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Oesophageal adenocarcinoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Seborrhoeic keratosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Squamous cell carcinoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Tumour pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	0
Vascular disorders
Aortic aneurysm
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Aortic occlusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Deep vein thrombosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Embolism
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Flushing
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	2	0	0	0	1	1	0	1	0
Hot flush
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Hypertension
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	1 / 4 (25.00%)	5 / 42 (11.90%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	1	3	1	7	0
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	1	2	1
Vena cava embolism
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	5 / 42 (11.90%)	1 / 21 (4.76%)
occurrences all number	1	0	0	0	0	0	1	7	1
Axillary pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Catheter site pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0
Chills
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	1	0	0	3	2
Cyst
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Facial pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Fatigue
subjects affected / exposed	1 / 4 (25.00%)	3 / 5 (60.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 9 (22.22%)	2 / 6 (33.33%)	4 / 4 (100.00%)	19 / 42 (45.24%)	6 / 21 (28.57%)
occurrences all number	2	3	1	1	2	3	4	25	7
Feeling hot
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Gait disturbance
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	1	0	0	0	0	2
Inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Influenza like illness
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	2	0	0	1
Infusion site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Malaise
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	1	0	0	0	1
Mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Mucosal inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	3	0	2	1
Nodule
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	1	1	0
Oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	1	1	2
Oedema peripheral
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 9 (33.33%)	0 / 6 (0.00%)	1 / 4 (25.00%)	5 / 42 (11.90%)	3 / 21 (14.29%)
occurrences all number	2	0	1	0	5	0	1	7	4
Pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0
Pyrexia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	3 / 9 (33.33%)	1 / 6 (16.67%)	2 / 4 (50.00%)	8 / 42 (19.05%)	2 / 21 (9.52%)
occurrences all number	0	0	2	0	3	1	2	12	3
Secretion discharge
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Temperature intolerance
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Immune system disorders
Allergy to arthropod sting
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Contrast media reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Reproductive system and breast disorders
Breast mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Erectile dysfunction
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Galactorrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Pruritus genital
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	5	0
Cough
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	3 / 6 (50.00%)	1 / 4 (25.00%)	9 / 42 (21.43%)	8 / 21 (38.10%)
occurrences all number	0	1	1	0	1	4	2	17	9
Dry throat
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Dysphonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	2	1
Dyspnoea
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 4 (0.00%)	7 / 42 (16.67%)	8 / 21 (38.10%)
occurrences all number	1	1	0	0	3	0	0	9	10
Dyspnoea exertional
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	1	0	0	1	0	0	0	1	1
Epistaxis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	1	0	3	3
Haemoptysis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0
Hiccups
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Hypoxia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Laryngeal obstruction
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Lung disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Nasal congestion
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	1	0	0	0	1	1	0	3	2
Oropharyngeal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Oropharyngeal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	2	0	0	2	2
Painful respiration
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Paranasal sinus hypersecretion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	1	0	0	2	1
Pneumonitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	2	3
Productive cough
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	7 / 42 (16.67%)	2 / 21 (9.52%)
occurrences all number	0	0	0	2	1	0	0	8	2
Pulmonary haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Rales
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Rhinitis allergic
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Rhinorrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	0 / 4 (0.00%)	4 / 42 (9.52%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	1	2	0	7	4
Sinus congestion
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	2	1	0	0	0	0	0	1	0
Sneezing
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Wheezing
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	1	0	1	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Anxiety
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	1	1	0	0	0	0	0	2	2
Confusional state
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Delirium
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Depression
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	1	0	0	0	2
Insomnia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	5 / 42 (11.90%)	3 / 21 (14.29%)
occurrences all number	0	0	0	1	0	0	0	5	3
Mood altered
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	5	0	1	3	3
Amylase decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Amylase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	1 / 4 (25.00%)	3 / 42 (7.14%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	1	1	1	6	8
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 42 (4.76%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	4	0	1	14	3
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	3	0	1	0	1	0	0	0	1
Blood bilirubin increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Blood creatine increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Blood creatinine increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	1 / 6 (16.67%)	1 / 4 (25.00%)	4 / 42 (9.52%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	3	1	1	5	6
Blood fibrinogen decreased
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0
Blood glucose increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Blood iron decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Blood phosphorus decreased
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Blood testosterone decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	2	2
Blood triglycerides increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	2	3
Blood urea increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Blood urine present
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
C-reactive protein increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	2	1
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
General physical condition abnormal
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
International normalised ratio increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Lipase increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	1 / 4 (25.00%)	4 / 42 (9.52%)	2 / 21 (9.52%)
occurrences all number	2	0	3	0	5	0	2	19	12
Lymphocyte count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1	0	0	1
Neutrophil count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	3	0
Platelet count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	2
Platelet count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Procalcitonin increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Prothrombin time prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1	0	0	1
Serum ferritin decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Tri-iodothyronine free abnormal
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Weight decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	0 / 4 (0.00%)	5 / 42 (11.90%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	1	0	7	0
Weight increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0
White blood cell count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0
White blood cell count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Eastern Cooperative Oncology Group performance status worsened
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0
Electrocardiogram T wave abnormal
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Influenza B virus test positive
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Injury, poisoning and procedural complications
Anaemia postoperative
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Arthropod bite
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Chemical burn of skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Contusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	3	1	0	0
Cystitis radiation
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
Fall
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	2 / 6 (33.33%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	1	0	2	1	2	0	2	0
Humerus fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Infusion related reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	4 / 42 (9.52%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	4	1
Post procedural oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Radiation skin injury
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Rib fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
Scratch
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	4	1
Spinal compression fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Sunburn
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Wound
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0
Atrial fibrillation
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	1	0	0	1	1
Cardiac failure congestive
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Palpitations
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Sinus tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	2 / 6 (33.33%)	1 / 4 (25.00%)	3 / 42 (7.14%)	4 / 21 (19.05%)
occurrences all number	0	0	0	0	1	3	3	3	4
Dysgeusia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0
Facial paralysis
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Head discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Headache
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 9 (22.22%)	0 / 6 (0.00%)	1 / 4 (25.00%)	6 / 42 (14.29%)	5 / 21 (23.81%)
occurrences all number	0	0	0	4	3	0	2	7	7
Hyperaesthesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	0	1	0	0	0	0	0	2	1
Hyposmia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Lethargy
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	2	1
Memory impairment
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Neuralgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0
Neuropathy peripheral
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Paraesthesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	5 / 42 (11.90%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	6	3
Peripheral sensory neuropathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	1	0	0	0	2
Sciatica
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Sensory disturbance
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Somnolence
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	3	0
Tremor
subjects affected / exposed	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	2	0	0	0	0	0	0	2	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 9 (33.33%)	0 / 6 (0.00%)	1 / 4 (25.00%)	6 / 42 (14.29%)	5 / 21 (23.81%)
occurrences all number	0	0	2	1	5	0	2	10	29
Iron deficiency anaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Leukocytosis
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Lymphopenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Ear and labyrinth disorders
Ear discomfort
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0
Ear disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Ear pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
Hypoacusis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Tinnitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Eye disorders
Asthenopia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Conjunctivitis allergic
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Diplopia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Dry eye
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Episcleritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Eye irritation
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	2	0	0	2	0
Eye pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Eye pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Eyelid ptosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Keratitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Lacrimation increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	2	0	2	1
Ocular hyperaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Periorbital swelling
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Photophobia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	1	0	2
Vision blurred
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	1	1	0	0
Visual impairment
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Abdominal distension
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	4	0
Abdominal mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Abdominal pain
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	4 / 42 (9.52%)	3 / 21 (14.29%)
occurrences all number	2	2	0	0	1	0	0	5	4
Abdominal pain lower
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	1	0	0	0	0	0	2
Abdominal pain upper
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	1	0	0	2	1
Aphthous ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	3
Colitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0
Constipation
subjects affected / exposed	1 / 4 (25.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	12 / 42 (28.57%)	6 / 21 (28.57%)
occurrences all number	1	2	0	1	0	2	0	16	7
Diarrhoea
subjects affected / exposed	1 / 4 (25.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 9 (33.33%)	5 / 6 (83.33%)	0 / 4 (0.00%)	15 / 42 (35.71%)	9 / 21 (42.86%)
occurrences all number	3	3	0	0	12	5	0	23	14
Dry mouth
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	0	0	0	4	3
Duodenitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Dyspepsia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	3 / 21 (14.29%)
occurrences all number	1	0	0	0	0	0	0	1	5
Dysphagia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	0	0	0	0	0	0	0	1
Epigastric discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Faeces soft
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0
Flatulence
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	2	1	0	0	0	1	0	3	0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Gingival bleeding
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	1	2
Gingival pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Immune-mediated enterocolitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Inguinal hernia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	5 / 9 (55.56%)	1 / 6 (16.67%)	3 / 4 (75.00%)	10 / 42 (23.81%)	7 / 21 (33.33%)
occurrences all number	3	1	1	3	7	3	4	13	8
Odynophagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Oral disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Oral pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	2	0	0	0	1
Pancreatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Rectal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	4	0
Stomatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	0	2
Vomiting
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 9 (22.22%)	2 / 6 (33.33%)	1 / 4 (25.00%)	11 / 42 (26.19%)	6 / 21 (28.57%)
occurrences all number	0	2	0	1	2	2	1	15	8
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Hepatocellular injury
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Hepatotoxicity
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Liver disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Alopecia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	2	0
Dermatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Dermatitis acneiform
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	1	0	1	0	1	0	2
Diabetic foot
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	4	0
Dry skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	5 / 42 (11.90%)	4 / 21 (19.05%)
occurrences all number	0	0	0	0	0	1	0	5	4
Ecchymosis
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	0	0	0	1	0	0	0	4
Macule
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Night sweats
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	1 / 4 (25.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	1	3	0
Pain of skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Papule
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Perioral dermatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	5 / 9 (55.56%)	0 / 6 (0.00%)	0 / 4 (0.00%)	7 / 42 (16.67%)	3 / 21 (14.29%)
occurrences all number	0	0	2	1	10	0	0	10	4
Rash
subjects affected / exposed	2 / 4 (50.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	4 / 9 (44.44%)	2 / 6 (33.33%)	0 / 4 (0.00%)	7 / 42 (16.67%)	4 / 21 (19.05%)
occurrences all number	2	1	0	1	4	2	0	9	4
Rash maculo-papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	4 / 21 (19.05%)
occurrences all number	0	0	0	0	0	0	0	5	5
Rash papular
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Rash pruritic
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Scar pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Skin discolouration
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Skin fissures
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Skin lesion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	1	2	1	1
Skin ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Urticaria
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Vitiligo
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Xeroderma
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	0	1	0	0	0	0	0	2	2
Micturition urgency
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Nocturia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Pollakiuria
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	1	0	0	0	0	0	0	2	2
Proteinuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Renal tubular necrosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Urinary incontinence
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Urinary retention
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Urinary tract pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Urine abnormality
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0
Hypercalcaemia of malignancy
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	4	0
Hyperthyroidism
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	1	0	0	0	0	1	1	1
Hypothyroidism
subjects affected / exposed	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	1 / 4 (25.00%)	4 / 42 (9.52%)	2 / 21 (9.52%)
occurrences all number	0	3	0	0	0	1	1	4	2
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 9 (22.22%)	2 / 6 (33.33%)	1 / 4 (25.00%)	10 / 42 (23.81%)	7 / 21 (33.33%)
occurrences all number	0	0	0	1	2	2	1	18	12
Arthritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0
Back pain
subjects affected / exposed	1 / 4 (25.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	1 / 6 (16.67%)	1 / 4 (25.00%)	10 / 42 (23.81%)	2 / 21 (9.52%)
occurrences all number	1	2	0	0	2	1	1	11	2
Bone lesion
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Flank pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 9 (22.22%)	1 / 6 (16.67%)	0 / 4 (0.00%)	4 / 42 (9.52%)	1 / 21 (4.76%)
occurrences all number	0	0	1	1	2	1	0	5	1
Groin pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Joint range of motion decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Joint swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Limb discomfort
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	2 / 6 (33.33%)	0 / 4 (0.00%)	6 / 42 (14.29%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	1	4	0	6	2
Muscular weakness
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	0	0	0	1	3
Musculoskeletal chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	4 / 42 (9.52%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	1	6	1
Musculoskeletal pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 9 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	5 / 42 (11.90%)	1 / 21 (4.76%)
occurrences all number	3	0	0	1	0	2	0	6	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Myalgia
subjects affected / exposed	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	6 / 42 (14.29%)	3 / 21 (14.29%)
occurrences all number	2	0	0	0	2	0	0	9	3
Neck pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Osteoarthritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	2 / 6 (33.33%)	0 / 4 (0.00%)	6 / 42 (14.29%)	4 / 21 (19.05%)
occurrences all number	0	1	0	0	0	2	0	7	5
Pain in jaw
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	1 / 4 (25.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Pathological fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Spinal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Tendon disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Infections and infestations
Abscess
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Bronchiolitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Bronchitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Conjunctivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Ear infection
subjects affected / exposed	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	3	0	0	0	0	0	0	0	0
Eye infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Gastrointestinal fungal infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Gingivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Herpes zoster
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Influenza
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Kidney infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Lower respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Lower respiratory tract infection bacterial
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Nasopharyngitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	3	0
Oral candidiasis
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0
Oral fungal infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Oral herpes
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Otitis media
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0
Rash pustular
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	2
Rhinitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Sinusitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	0	0	0	0	3
Tooth abscess
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Tooth infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 9 (22.22%)	3 / 6 (50.00%)	0 / 4 (0.00%)	3 / 42 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	3	4	0	5	0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 9 (11.11%)	0 / 6 (0.00%)	1 / 4 (25.00%)	2 / 42 (4.76%)	4 / 21 (19.05%)
occurrences all number	0	1	0	2	1	0	1	2	5
Viral infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	1	0	0	0	0	0	0	1
Viral upper respiratory tract infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	1 / 6 (16.67%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Decreased appetite
subjects affected / exposed	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	2 / 9 (22.22%)	2 / 6 (33.33%)	0 / 4 (0.00%)	5 / 42 (11.90%)	1 / 21 (4.76%)
occurrences all number	2	1	2	0	2	4	0	5	1
Dehydration
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	0 / 4 (0.00%)	2 / 42 (4.76%)	1 / 21 (4.76%)
occurrences all number	1	0	0	0	1	1	0	3	2
Glucose tolerance impaired
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	1	1
Gout
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Hypercalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	1 / 6 (16.67%)	0 / 4 (0.00%)	6 / 42 (14.29%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	1	1	0	9	2
Hyperglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0
Hyperkalaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	3	0	0	3	5
Hypermagnesaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Hyperuricaemia
subjects affected / exposed	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 9 (11.11%)	0 / 6 (0.00%)	0 / 4 (0.00%)	2 / 42 (4.76%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	3	0
Hypocalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Hypoglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Hypokalaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 4 (0.00%)	5 / 42 (11.90%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	4	0	0	6	2
Hypomagnesaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	0 / 6 (0.00%)	0 / 4 (0.00%)	4 / 42 (9.52%)	2 / 21 (9.52%)
occurrences all number	0	0	0	0	2	0	0	9	6
Hyponatraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 9 (22.22%)	1 / 6 (16.67%)	0 / 4 (0.00%)	3 / 42 (7.14%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	3	1	0	4	5
Hypophosphataemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	3 / 21 (14.29%)
occurrences all number	0	0	0	0	0	0	0	1	8
Metabolic alkalosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	0 / 42 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	1
Type 2 diabetes mellitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 9 (0.00%)	0 / 6 (0.00%)	0 / 4 (0.00%)	1 / 42 (2.38%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0

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Were there any global substantial amendments to the protocol? Yes

16 Apr 2014

Name AMP 514 was replaced with MEDI0680. Specified that immunotherapy-naïve and pretreated participants were to be enrolled in up to 8 hematologic and solid tumor cohorts and that the immunotherapy naïve and pretreated cohorts could enroll an additional 60 participants based on emerging efficacy and safety data from the current study and ongoing studies. Specified that each hematologic cohort, including MDS, would only be expanded after submission of a formal protocol amendment. Updated the inclusion criteria to include NSCLC participants must have failed to respond or relapsed following platinum containing doublet chemotherapy.

01 Oct 2014

To align with strategy of study focus the tumor types were limited to non-small cell lung cancer, squamous cell carcinoma of the head and neck, microsatellite instability-high colorectal cancer, bladder cancer, ovarian cancer, esophageal cancer, gastric cancer, and renal cell carcinoma in the dose-escalation phase. Added 20 mg/kg MEDI0680 plus 10 mg/kg durvalumab cohort to the Q2W dose-escalation schedule. Revised the dose-escalation phase to allow for any dose-escalation cohort that has not exceeded the MTD to be expanded by up to a maximum of 18 participants. Updated the inclusion criteria as: Revised to reflect the solid tumor types that would be allowed in the dose escalation phase. Indicated that no more than 3 prior lines of systemic therapy would be allowed in the recurrent or metastatic setting; added specific inclusion criteria for NSCLC participants in dose-escalation and dose-expansion; and added that participants with previously treated CNS metastases must be radiographically and neurologically stable for at least 6 weeks.

11 Feb 2016

Dose-expansion phase updated to enroll PD-L1 positive immunotherapy-naïve participants with RCC, added MEDI0680 monotherapy as a comparator arm; revised primary objective to evaluate antitumor activity based on investigator assessed response and secondary objectives to describe safety and tolerability, and to evaluate antitumor activity based on BICR assessed response in immunotherapy-naïve participants with advanced or metastatic ccRCC. Removed exploratory objective on patient reported outcomes. Replaced primary endpoint of maximum tolerated dose with presence of AEs, SAEs, laboratory parameters, vital signs, physical examinations, and ECG results. Added endpoint of PD-L1 expression/localization on tumor membrane and tumor infiltrating immune cells within tumor microenvironment. Increased sample size to 156 and study centers to 80. Participants in dose expansion phase were not to be replaced. Updated safety assessment. Added Appendix of Dose Modifications for Toxicity Management.

27 May 2016

Revised the exclusion criteria to permit enrollment of participants with prior endocrine toxicities who are stable on replacement therapy.

29 Mar 2017

Removed MEDI0680 monotherapy arm in the dose-expansion phase and replaced with a nivolumab monotherapy arm. Clarified that OR is the primary endpoint and that OS is a secondary endpoint in the dose expansion phase. Reduced the planned sample size from 156 to approximately 96 participants for both dose-escalation and dose-expansion phases; from 120 to approximately 60 in dose-expansion phases; and study center numbers from 80 to 50. Added an interim futility analysis for the MEDI0680/durvalumab combination therapy arm in the dose-expansion phase after 20 participants have been randomized and have reached their second post baseline disease assessment or have completed the study. Changed the randomization ratio of combination and monotherapy from 1:1 to 2:1. Revised end of study definition from 3 years to 2 years after the last participant was enrolled and added possible treatment options for participants still receiving treatment at the end of the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Study did not meet primary endpoint, so, BICR data for antitumor activity were not collected. Numeric data were not collected for “Change from baseline in target lesion” as it was to be analysed by Spider plots per Statistical Analysis Plan.

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Clinical trials

Clinical Trial Results: A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Subjects with Select Advanced Malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase

Primary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase

Primary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase

Primary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase

Primary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase

Primary: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase

Primary: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase

Primary: Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose-expansion Phase

Primary: Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) in Dose-expansion Phase

Secondary: Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

Secondary: Overall Survival in Dose-expansion Phase

Secondary: Overall Survival in Dose-expansion Phase

Secondary: BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase

Secondary: OS in Dose-escalation Phase

Secondary: OS in Dose-escalation Phase

Secondary: Number of Participants With TEAEs and TESAEs in Dose-expansion Phase

Secondary: Number of Participants With TEAEs and TESAEs in Dose-expansion Phase

Secondary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase

Secondary: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase

Secondary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase

Secondary: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase

Secondary: Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase

Secondary: Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase

Secondary: Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases

Secondary: Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases

Secondary: Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases

Secondary: Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases

Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases

Secondary: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases

Secondary: Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases

Secondary: Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases

Secondary: ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase

Secondary: ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Subjects with Select Advanced Malignancies