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Clinical Trial Results:
A Phase 2, Fast Real-time Assessment of Combination Therapies in Immuno-ONcology Study in Subjects with Advanced Non-small Cell Lung Cancer (FRACTION-Lung)

Summary
EudraCT number	2016-001835-11
Trial protocol	ES AT FR IT
Global end of trial date	29 Jan 2020

Results information
Results version number	v1(current)
This version publication date	12 Feb 2021
First version publication date	12 Feb 2021
Other versions

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

CA018-001

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chaussée de la Hulpe 185, Brussels, Belgium, 1170

Public contact

EU Study Start-Up Unit, Bristol-Myers Squibb International Corporation, Clinical.Trials@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, Clinical.Trials@bms.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

17 Mar 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

29 Jan 2020

Was the trial ended prematurely?

Main objective of the trial

To evaluate the preliminary efficacy, safety, and tolerability of novel FRACTION-Lung treatment combinations in subjects with advanced non-small cell lung cancer (NSCLC).

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

06 May 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 2

Country: Number of subjects enrolled

Australia: 6

Country: Number of subjects enrolled

Canada: 23

Country: Number of subjects enrolled

France: 4

Country: Number of subjects enrolled

Italy: 25

Country: Number of subjects enrolled

Spain: 28

Country: Number of subjects enrolled

Switzerland: 1

Country: Number of subjects enrolled

United States: 206

Worldwide total number of subjects

295

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)

149

From 65 to 84 years

146

85 years and over

Subject disposition

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Recruitment details

Screening details

Each of the 295 subjects was assigned to 1 of 5 non-consecutive Tracks (based on previous therapy exposure and/or PD-1/PD-L1 expression). 14 of the 295 subjects, after receiving initial treatment, were re-randomized to a second, different treatment (either under a different Track or within the same Track).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Nivolumab

Arm description

Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks)

Arm type

Experimental

Investigational medicinal product name

Nivolumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Flat dose 240 mg Q2W given as an IV over approximately 30 minutes

Nivolumab + Dasatinib

Arm description

Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)

Arm type

Experimental

Investigational medicinal product name

Nivolumab + Dasatinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection, Tablet

Routes of administration

Intravenous use, Oral use

Dosage and administration details

Nivolumab: flat dose 240 mg Q2W Dasatinib: 100 mg QD

Nivolumab + BMS986016

Arm description

Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks)

Arm type

Experimental

Investigational medicinal product name

Nivolumab + BMS986016

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Nivolumab: flat dose 240 mg Q2W BMS986016: 20 mg Q2W

Nivolumab + Ipilimumab

Arm description

Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study

Arm type

Experimental

Investigational medicinal product name

Nivolumab + Ipilimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Nivolumab: flat dose 240 mg Q2W Ipilimumab: 1 mg/Kg Q6W

Nivolumab + BMS986205

Arm description

Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks

Arm type

Experimental

Investigational medicinal product name

Nivolumab + BMS986205

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection, Tablet

Routes of administration

Intravenous use, Oral use

Dosage and administration details

Nivolumab: flat dose 240 mg Q2W BMS986205: 100 mg QD

Number of subjects in period 1	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Started	49	104	17	88	37
Completed	16	9	1	26	0
Not completed	33	97	17	67	43
Subject withdrew consent	-	5	1	-	-
Disease progression	24	63	15	52	34
Subject request to discontinue	1	3	-	1	3
Study drug toxicity	5	12	-	9	2
Death	-	-	-	1	-
AE unrelated to study drug	2	6	1	1	2
Other reasons	1	8	-	3	2
Joined	0	2	1	5	6
Re-randomized to a second treatment	-	2	1	5	6

Baseline characteristics

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Reporting group title

Nivolumab

Reporting group description

Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + Dasatinib

Reporting group description

Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + BMS986016

Reporting group description

Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + Ipilimumab

Reporting group description

Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study

Reporting group title

Nivolumab + BMS986205

Reporting group description

Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks

Notes
[1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
Justification: 14 subjects, after receiving a first treatment, were re-randomized to a second different treatment group

Reporting group values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205	Total
Number of subjects	49	106	18	93	43	309
Age categorical
Units: Subjects
Adults (18-64 years)	24	49	8	51	22	154
From 65-84 years	25	57	10	42	21	155
Age Continuous
Units: Years
arithmetic mean (standard deviation)	64.5 ( 10.27 )	63.8 ( 9.26 )	66.3 ( 8.99 )	62.4 ( 8.88 )	64.5 ( 8.05 )	-
Sex: Female, Male
Units: Participants
Female	21	35	8	39	22	125
Male	28	71	10	54	21	184
Race (NIH/OMB)
Units: Subjects
Asian	2	7	2	3	4	18
Black or African American	0	6	1	6	7	20
White	42	87	15	82	30	256
Unknown or Not Reported	5	6	0	2	2	15
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	2	0	5	1	9
Not Hispanic or Latino	25	66	18	63	31	203
Unknown or Not Reported	23	38	0	25	11	97

End points

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Reporting group title

Nivolumab

Reporting group description

Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + Dasatinib

Reporting group description

Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + BMS986016

Reporting group description

Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + Ipilimumab

Reporting group description

Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study

Reporting group title

Nivolumab + BMS986205

Reporting group description

Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks

Primary: Objective Response Rate (ORR)

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End point title

Objective Response Rate (ORR) ^[1]

End point description

ORR is defined as the percentage of subjects whose confirmed best overall response (BOR) is either a complete response (CR) or partial response (PR). BOR was assessed by investigator per RECIST1.1. Results are presented by study tracks. IO YES/NO = Prior immuno-oncology therapy exposure status. PD-L1 + = PD-L1 expression levels >=1%. PD-L1 - = PD-L1 expression levels <1%. Results for treatment groups not receiving treatment during a specific study track are indicated as 99999.

End point type

Primary

End point timeframe

From first dose to 2 years following last dose (up to 30 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: ORR is estimated and corresponding exact two-sided 95% CI is derived based Clopper and Pearson method.

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	49 ^[2]	106 ^[3]	18 ^[4]	93 ^[5]	43 ^[6]
Units: Percent of Subjects
number (confidence interval 95%)
Track 1 = NO IO - PD-L1 +	17.5 (7.3 to 32.8)	25.0 (0.6 to 80.6)	99999 (99999 to 99999)	0 (0.0 to 70.8)	9999 (9999 to 9999)
Track 2 = NO IO - PD-L1 -	0 (0.0 to 33.6)	0 (0.0 to 33.6)	0 (0.0 to 84.2)	25.0 (5.5 to 57.2)	99999 (99999 to 99999)
Track 3 = YES IO	99999 (99999 to 99999)	2.4 (0.1 to 12.9)	0 (0.0 to 20.6)	5.6 (0.1 to 27.3)	99999 (99999 to 99999)
Track 4 = NO IO (after enrollment stop in 1,2,3)	99999 (99999 to 99999)	1.9 (0.0 to 10.1)	99999 (99999 to 99999)	20.0 (10.8 to 32.3)	99999 (99999 to 99999)
Track 5 = YES IO (after enrollment stop in 1,2,3)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	2.3 (0.1 to 12.3)

Notes
[2] - Track1=40 Track2=9 Track3=0 Track4=0 Track5=0
[3] - Track1=4 Track2=8 Track3=41 Track4=53 Track5=0
[4] - Track1=0 Track2=2 Track3=16 Track4=0 Track5=0
[5] - Track1=3 Track2=12 Track3=18 Track4=60 Track5=0
[6] - Track1=0 Track2=0 Track3=0 Track4=0 Track5=43

No statistical analyses for this end point

Primary: Duration of Response (DOR)

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End point title

Duration of Response (DOR) ^[7]

End point description

DOR, computed for all treated subjects with a confirmed BOR of CR or PR, is defined as the time between the date of first response and the date of first documented disease progression (as determined by RECIST 1.1) or death due to any cause. Results are presented by study tracks. IO YES/NO = Prior immuno-oncology therapy exposure status. PD-L1 + = PD-L1 expression levels >=1%. PD-L1 - = PD-L1 expression levels <1%. Results for treatment groups not receiving treatment during a specific study track or for which a value was not calculable are indicated as 99999.

End point type

Primary

End point timeframe

From first dose to 2 years following last dose (up to 30 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: DOR is estimated using the Kaplan-Meier (KM) product limit method. Median values of DOR, along with two-sided 95% CI, is computed based on a log-log transformation method.

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	7 ^[8]	3 ^[9]	0 ^[10]	16 ^[11]	1 ^[12]
Units: Months
median (confidence interval 95%)
Track 1 =NO IO - PD-L1 +	12.81 (0.03 to 99999)	8.57 (-99999 to 99999)	( to )	99999 (99999 to 99999)	99999 (99999 to 99999)
Track 2 = NO IO - PD-L1 -	99999 (99999 to 99999)	99999 (99999 to 99999)	( to )	99999 (99999 to 99999)	99999 (99999 to 99999)
Track 3 = YES IO	99999 (99999 to 99999)	99999 (99999 to 99999)	( to )	99999 (99999 to 99999)	99999 (99999 to 99999)
Track 4 = NO IO (after enrollment stop in 1,2,3)	99999 (99999 to 99999)	99999 (99999 to 99999)	( to )	12.65 (8.77 to 99999)	99999 (99999 to 99999)
Track 5 = YES IO (after enrollment stop in 1,2,3)	99999 (99999 to 99999)	99999 (99999 to 99999)	( to )	99999 (99999 to 99999)	3.75 (-99999 to 99999)

Notes
[8] - Track1=7 Track2=0 Track3=0 Track4=0 Track5=0
[9] - Track1=1 Track2=0 Track3=1 Track4=1 Track5=0
[10] - Track1=0 Track2=0 Track3=0 Track4=0 Track5=0
[11] - Track1=0 Track2=3 Track3=1 Track4=12 Track5=0
[12] - Track1=0 Track2=0 Track3=0 Track4=0 Track5=1

No statistical analyses for this end point

Primary: Progression Free Survival Rate (PFSR) at 24 Weeks

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End point title

Progression Free Survival Rate (PFSR) at 24 Weeks ^[13]

End point description

The PFSR at 24 weeks is defined as the proportion of treated subjects remaining progression free and surviving at 24 weeks since the first dosing date. Results are presented by study tracks and only for the treatment groups with a sufficient number of subjects remaining progression-free during the timeframe (n>=5). IO YES/NO = Prior immuno-oncology therapy exposure status. PD-L1 + = PD-L1 expression levels >=1%. PD-L1 - = PD-L1 expression levels <1%. Results for treatment groups not receiving treatment during a specific study track or with an insufficient number of subjects remaining progression-free are indicated as 99999.

End point type

Primary

End point timeframe

From first dose to 24 weeks after first dose

Notes
[13] - 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: PFSR at 24 weeks is derived from the Kaplan Meier estimate and corresponding CIs are derived based on Greenwood formula for variance derivation and on log-log transformation applied on the survivor function.

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	49 ^[14]	106 ^[15]	18 ^[16]	93 ^[17]	43 ^[18]
Units: Proportion of Participants
number (confidence interval 95%)
Track 1 = NO IO - PD-L1 +	0.302 (0.164 to 0.451)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)
Track 2 = NO IO - PD-L1 -	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	0.455 (0.167 to 0.707)	99999 (99999 to 99999)
Track 3 = YES IO	99999 (99999 to 99999)	0.191 (0.079 to 0.340)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)
Track 4 = NO IO (after enrollment stop in 1,2,3)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	0.391 (0.265 to 0.514)	99999 (99999 to 99999)
Track 5 = YES IO (after enrollment stop in 1,2,3)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	99999 (99999 to 99999)	0.111 (0.036 to 0.235)

Notes
[14] - Track1=40 Track2=9 Track3=0 Track4=0 Track5=0
[15] - Track1=4 Track2=8 Track3=41 Track4=53 Track5=0
[16] - Track1=0 Track2=2 Track3=16 Track4=0 Track5=0
[17] - Track1=3 Track2=12 Track3=18 Track4=60 Track5=0
[18] - Track1=0 Track2=0 Track3=0 Track4=0 Track5=43

No statistical analyses for this end point

Secondary: Percentage of Subjects Experiencing Adverse Events (AEs)

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End point title

Percentage of Subjects Experiencing Adverse Events (AEs)

End point description

This outcome measure describes the percentage of subjects who experienced any grade, all causality AEs during the specified time frame

End point type

Secondary

End point timeframe

From first dose to 100 days following last dose

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	49	106	18	93	43
Units: Percent of Subjects
number (not applicable)	100.0	100.0	100.0	98.9	100.0

No statistical analyses for this end point

Secondary: Percentage of Subjects Experiencing Serious Adverse Events (SAEs)

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End point title

Percentage of Subjects Experiencing Serious Adverse Events (SAEs)

End point description

This outcome measure describes the percentage of subjects who experienced any grade, all causality SAEs during the specified time frame

End point type

Secondary

End point timeframe

From first dose to 100 days following last dose

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	49	106	18	93	43
Units: Percent of Subjects
number (not applicable)	57.1	53.8	61.1	58.1	60.5

No statistical analyses for this end point

Secondary: Percentage of Subjects Experiencing Adverse Events (AEs) Leading to Discontinuation

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End point title

Percentage of Subjects Experiencing Adverse Events (AEs) Leading to Discontinuation

End point description

This outcome measure describes the percentage of subjects who experienced all causality AEs leading to discontinuation of study therapy during the specified time frame

End point type

Secondary

End point timeframe

From first dose to 100 days following last dose

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	49	106	18	93	43
Units: Percent of Subjects
number (not applicable)	14.3	23.6	5.6	11.8	14.0

No statistical analyses for this end point

Secondary: Percentage of Subjects Experiencing Death

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End point title

Percentage of Subjects Experiencing Death

End point description

This outcome measure describes the percentage of subjects who died (due to any cause) during the specified time frame

End point type

Secondary

End point timeframe

From first dose to up to 45 months following first dose

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	49	106	18	93	43
Units: Percent of Subjects
number (not applicable)	57.1	55.7	66.7	46.2	62.8

No statistical analyses for this end point

Secondary: Number of Subjects Experiencing Laboratory Abnormalities in Hepatic Tests

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End point title

Number of Subjects Experiencing Laboratory Abnormalities in Hepatic Tests

End point description

The following measurements will be considered laboratory abnormalities for hepatic tests: - ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN - Total bilirubin > 2 x ULN - Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN - Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN ALT=Alanine aminotransferase AST=Aspartate aminotransferase ULN=Upper Limit of Normal

End point type

Secondary

End point timeframe

From first dose to 100 days following last dose

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	49	106	18	93	43
Units: Subjects
ALT OR AST > 3XULN	4	3	1	5	3
ALT OR AST > 5XULN	2	0	0	3	2
ALT OR AST > 10XULN	2	0	0	1	2
ALT OR AST > 20XULN	0	0	0	1	1
TOTAL BILIRUBIN > 2XULN	1	0	0	2	3
(1 day) ALT or AST>3x ULN and total bilir.>2x ULN	0	0	0	2	2
(30 day) ALT or AST>3x ULN and total bilir.>2x ULN	0	0	0	2	2

No statistical analyses for this end point

Secondary: Number of Subjects Experiencing Laboratory Abnormalities in Thyroid Tests

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End point title

Number of Subjects Experiencing Laboratory Abnormalities in Thyroid Tests

End point description

The following measurements will be considered laboratory abnormalities for thyroid tests: - TSH value > ULN and - With baseline TSH value ≤ ULN - At least one T3/T4 test value < LLN - Low TSH < LLN and - With baseline TSH value ≥ LLN - At least one T3/T4 test value > ULN TSH = thyroid stimulating hormone ULN=Upper Limit of Normal LLN=Lower Limit of Normal T3=Triiodothyronine T4=Thyroxin

End point type

Secondary

End point timeframe

From first dose to 100 days following last dose

End point values	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Number of subjects analysed	29	76	14	75	35
Units: Subjects
TSH > ULN	9	16	3	24	9
TSH > ULN WITH TSH <= ULN AT BASELINE	6	9	1	17	6
TSH > ULN AT LEAST 1 FT3/FT4 VALUE < LLN	4	3	1	8	6
TSH < LLN	5	3	0	20	4
TSH < LLN WITH TSH >= LLN AT BASELINE	5	1	0	16	4
TSH < LLN AT LEAST 1 FT3/FT4 VALUE > ULN	3	1	0	5	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Deaths = collected from first dose to up to 45 months following first dose Serious adverse events and other adverse events = collected from start of treatment up to 100 days of discontinuation of dosing.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

Nivolumab

Reporting group description

Nivolumab monotherapy 240 mg Q2W administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + Dasatinib

Reporting group description

Nivolumab 240 mg Q2W + Dasatinib 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + BMS986016

Reporting group description

Nivolumab 240 mg Q2W + BMS986016 20 mg Q2W, administered until completion of 6 cycles (1 cycle=4 weeks)

Reporting group title

Nivolumab + Ipilimumab

Reporting group description

Nivolumab 240 mg Q2W for 12 doses + Ipilimumab 1 mg/kg Q6W for 4 doses, administered until completion of 24 weeks of study

Reporting group title

Nivolumab + BMS986205

Reporting group description

Nivolumab 480 mg Q4W + BMS986205 100 mg QD, administered until completion of 6 cycles (1 cycle=4 weeks)

Serious adverse events	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Total subjects affected by serious adverse events
subjects affected / exposed	28 / 49 (57.14%)	57 / 106 (53.77%)	11 / 18 (61.11%)	54 / 93 (58.06%)	26 / 43 (60.47%)
number of deaths (all causes)	28	59	12	43	27
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Cancer pain
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Malignant neoplasm progression
subjects affected / exposed	12 / 49 (24.49%)	29 / 106 (27.36%)	4 / 18 (22.22%)	20 / 93 (21.51%)	13 / 43 (30.23%)
occurrences causally related to treatment / all	0 / 12	0 / 30	0 / 4	0 / 20	0 / 15
deaths causally related to treatment / all	0 / 11	0 / 27	0 / 4	0 / 20	0 / 12
Malignant pleural effusion
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Metastases to meninges
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Neoplasm progression
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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 / 1
Second primary malignancy
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Tumour pain
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Hypotension
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Superior vena cava syndrome
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
General disorders and administration site conditions
Euthanasia
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 49 (2.04%)	2 / 106 (1.89%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Influenza like illness
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Oedema peripheral
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Pain
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 49 (0.00%)	3 / 106 (2.83%)	0 / 18 (0.00%)	3 / 93 (3.23%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 0	1 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Scrotal oedema
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	4 / 93 (4.30%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
Atelectasis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Bronchial obstruction
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Chronic obstructive pulmonary disease
subjects affected / exposed	2 / 49 (4.08%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	2 / 49 (4.08%)	7 / 106 (6.60%)	0 / 18 (0.00%)	5 / 93 (5.38%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 8	0 / 0	2 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Lung consolidation
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Oesophagobronchial fistula
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Pleural effusion
subjects affected / exposed	2 / 49 (4.08%)	7 / 106 (6.60%)	0 / 18 (0.00%)	3 / 93 (3.23%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 2	3 / 7	0 / 0	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	3 / 49 (6.12%)	6 / 106 (5.66%)	1 / 18 (5.56%)	3 / 93 (3.23%)	3 / 43 (6.98%)
occurrences causally related to treatment / all	3 / 3	6 / 8	1 / 1	3 / 3	3 / 4
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	4 / 49 (8.16%)	0 / 106 (0.00%)	1 / 18 (5.56%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
Respiratory distress
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 49 (2.04%)	2 / 106 (1.89%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 1	1 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
Psychiatric disorders
Confusional state
subjects affected / exposed	2 / 49 (4.08%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood bilirubin increased
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Human chorionic gonadotropin positive
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Transaminases increased
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Humerus fracture
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Overdose
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	1 / 93 (1.08%)	2 / 43 (4.65%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Toxicity to various agents
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	3 / 93 (3.23%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	1 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac tamponade
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Myocarditis
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Pericardial effusion
subjects affected / exposed	3 / 49 (6.12%)	1 / 106 (0.94%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 3	1 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Nervous system disorders
Brachial plexopathy
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral ischaemia
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Cerebrovascular accident
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	1 / 18 (5.56%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 2	1 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Haemorrhage intracranial
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Ischaemic stroke
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Peripheral sensory neuropathy
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	2 / 43 (4.65%)
occurrences causally related to treatment / all	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
Polyneuropathy
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Seizure
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Eye disorders
Vision blurred
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Visual impairment
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 3	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Diarrhoea
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Nausea
subjects affected / exposed	0 / 49 (0.00%)	3 / 106 (2.83%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal food impaction
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peritoneal haemorrhage
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Vomiting
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis acute
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Hepatitis
subjects affected / exposed	2 / 49 (4.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperbilirubinaemia
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoparathyroidism
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Hypophysitis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 49 (4.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Flank pain
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Muscular weakness
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Osteolysis
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Pain in extremity
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Sjogren's syndrome
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Brain abscess
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Enterocolitis infectious
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Influenza
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Pharyngitis streptococcal
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Pneumonia
subjects affected / exposed	3 / 49 (6.12%)	2 / 106 (1.89%)	0 / 18 (0.00%)	5 / 93 (5.38%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 3	2 / 3	0 / 0	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Post procedural infection
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	1 / 18 (5.56%)	2 / 93 (2.15%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	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
Urinary tract infection
subjects affected / exposed	1 / 49 (2.04%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Diabetes mellitus
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Diabetic ketoacidosis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	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
Failure to thrive
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	1 / 18 (5.56%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	1 / 49 (2.04%)	2 / 106 (1.89%)	0 / 18 (0.00%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Nivolumab	Nivolumab + Dasatinib	Nivolumab + BMS986016	Nivolumab + Ipilimumab	Nivolumab + BMS986205
Total subjects affected by non serious adverse events
subjects affected / exposed	46 / 49 (93.88%)	98 / 106 (92.45%)	18 / 18 (100.00%)	91 / 93 (97.85%)	41 / 43 (95.35%)
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	2 / 49 (4.08%)	1 / 106 (0.94%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	2	1	1	0	0
Hypertension
subjects affected / exposed	2 / 49 (4.08%)	6 / 106 (5.66%)	0 / 18 (0.00%)	5 / 93 (5.38%)	6 / 43 (13.95%)
occurrences all number	2	9	0	7	7
Hypotension
subjects affected / exposed	3 / 49 (6.12%)	2 / 106 (1.89%)	0 / 18 (0.00%)	6 / 93 (6.45%)	2 / 43 (4.65%)
occurrences all number	3	2	0	8	2
General disorders and administration site conditions
Asthenia
subjects affected / exposed	7 / 49 (14.29%)	18 / 106 (16.98%)	0 / 18 (0.00%)	11 / 93 (11.83%)	1 / 43 (2.33%)
occurrences all number	9	21	0	16	1
Chest discomfort
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	2 / 18 (11.11%)	3 / 93 (3.23%)	1 / 43 (2.33%)
occurrences all number	0	2	2	3	1
Chest pain
subjects affected / exposed	4 / 49 (8.16%)	7 / 106 (6.60%)	1 / 18 (5.56%)	5 / 93 (5.38%)	2 / 43 (4.65%)
occurrences all number	5	7	1	6	3
Chills
subjects affected / exposed	0 / 49 (0.00%)	11 / 106 (10.38%)	1 / 18 (5.56%)	5 / 93 (5.38%)	1 / 43 (2.33%)
occurrences all number	0	15	1	5	3
Early satiety
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	1 / 18 (5.56%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences all number	0	2	1	1	0
Fatigue
subjects affected / exposed	17 / 49 (34.69%)	51 / 106 (48.11%)	5 / 18 (27.78%)	44 / 93 (47.31%)	20 / 43 (46.51%)
occurrences all number	24	53	5	52	25
Oedema
subjects affected / exposed	0 / 49 (0.00%)	7 / 106 (6.60%)	0 / 18 (0.00%)	1 / 93 (1.08%)	2 / 43 (4.65%)
occurrences all number	0	8	0	1	2
Oedema peripheral
subjects affected / exposed	7 / 49 (14.29%)	8 / 106 (7.55%)	1 / 18 (5.56%)	8 / 93 (8.60%)	7 / 43 (16.28%)
occurrences all number	9	9	1	10	9
Pyrexia
subjects affected / exposed	4 / 49 (8.16%)	18 / 106 (16.98%)	1 / 18 (5.56%)	15 / 93 (16.13%)	5 / 43 (11.63%)
occurrences all number	6	30	1	23	7
Non-Cardiac chest pain
subjects affected / exposed	1 / 49 (2.04%)	6 / 106 (5.66%)	0 / 18 (0.00%)	5 / 93 (5.38%)	0 / 43 (0.00%)
occurrences all number	1	6	0	6	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	1	1	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	12 / 49 (24.49%)	21 / 106 (19.81%)	2 / 18 (11.11%)	25 / 93 (26.88%)	11 / 43 (25.58%)
occurrences all number	14	24	2	28	11
Dyspnoea
subjects affected / exposed	16 / 49 (32.65%)	34 / 106 (32.08%)	1 / 18 (5.56%)	27 / 93 (29.03%)	6 / 43 (13.95%)
occurrences all number	18	40	1	32	9
Dyspnoea exertional
subjects affected / exposed	2 / 49 (4.08%)	8 / 106 (7.55%)	2 / 18 (11.11%)	4 / 93 (4.30%)	1 / 43 (2.33%)
occurrences all number	2	8	2	4	1
Haemoptysis
subjects affected / exposed	6 / 49 (12.24%)	8 / 106 (7.55%)	0 / 18 (0.00%)	4 / 93 (4.30%)	2 / 43 (4.65%)
occurrences all number	7	8	0	6	2
Hypoxia
subjects affected / exposed	2 / 49 (4.08%)	6 / 106 (5.66%)	0 / 18 (0.00%)	6 / 93 (6.45%)	1 / 43 (2.33%)
occurrences all number	2	6	0	6	2
Nasal congestion
subjects affected / exposed	1 / 49 (2.04%)	2 / 106 (1.89%)	0 / 18 (0.00%)	5 / 93 (5.38%)	1 / 43 (2.33%)
occurrences all number	1	2	0	5	1
Oropharyngeal pain
subjects affected / exposed	2 / 49 (4.08%)	1 / 106 (0.94%)	0 / 18 (0.00%)	5 / 93 (5.38%)	0 / 43 (0.00%)
occurrences all number	2	1	0	6	0
Pleural effusion
subjects affected / exposed	2 / 49 (4.08%)	20 / 106 (18.87%)	1 / 18 (5.56%)	4 / 93 (4.30%)	3 / 43 (6.98%)
occurrences all number	2	26	1	4	3
Pneumonia aspiration
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0
Pneumonitis
subjects affected / exposed	1 / 49 (2.04%)	3 / 106 (2.83%)	1 / 18 (5.56%)	4 / 93 (4.30%)	2 / 43 (4.65%)
occurrences all number	1	4	1	4	3
Productive cough
subjects affected / exposed	7 / 49 (14.29%)	11 / 106 (10.38%)	0 / 18 (0.00%)	7 / 93 (7.53%)	2 / 43 (4.65%)
occurrences all number	9	13	0	8	2
Pulmonary embolism
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	1 / 18 (5.56%)	3 / 93 (3.23%)	0 / 43 (0.00%)
occurrences all number	0	2	1	3	0
Wheezing
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	6 / 93 (6.45%)	2 / 43 (4.65%)
occurrences all number	0	0	0	6	2
Upper-Airway cough syndrome
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	1 / 18 (5.56%)	3 / 93 (3.23%)	1 / 43 (2.33%)
occurrences all number	0	1	1	3	1
Psychiatric disorders
Anxiety
subjects affected / exposed	7 / 49 (14.29%)	15 / 106 (14.15%)	0 / 18 (0.00%)	8 / 93 (8.60%)	2 / 43 (4.65%)
occurrences all number	7	15	0	9	2
Confusional state
subjects affected / exposed	3 / 49 (6.12%)	5 / 106 (4.72%)	0 / 18 (0.00%)	3 / 93 (3.23%)	2 / 43 (4.65%)
occurrences all number	4	5	0	3	2
Depression
subjects affected / exposed	2 / 49 (4.08%)	5 / 106 (4.72%)	0 / 18 (0.00%)	5 / 93 (5.38%)	0 / 43 (0.00%)
occurrences all number	2	5	0	5	0
Insomnia
subjects affected / exposed	7 / 49 (14.29%)	11 / 106 (10.38%)	0 / 18 (0.00%)	12 / 93 (12.90%)	5 / 43 (11.63%)
occurrences all number	8	11	0	12	6
Investigations
Alanine aminotransferase increased
subjects affected / exposed	4 / 49 (8.16%)	8 / 106 (7.55%)	0 / 18 (0.00%)	5 / 93 (5.38%)	5 / 43 (11.63%)
occurrences all number	5	8	0	5	6
Amylase increased
subjects affected / exposed	4 / 49 (8.16%)	8 / 106 (7.55%)	1 / 18 (5.56%)	8 / 93 (8.60%)	0 / 43 (0.00%)
occurrences all number	7	9	1	9	0
Aspartate aminotransferase increased
subjects affected / exposed	6 / 49 (12.24%)	7 / 106 (6.60%)	1 / 18 (5.56%)	6 / 93 (6.45%)	4 / 43 (9.30%)
occurrences all number	7	7	1	6	4
Blood alkaline phosphatase increased
subjects affected / exposed	3 / 49 (6.12%)	3 / 106 (2.83%)	0 / 18 (0.00%)	4 / 93 (4.30%)	1 / 43 (2.33%)
occurrences all number	3	3	0	6	1
Blood bilirubin increased
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	4 / 43 (9.30%)
occurrences all number	0	0	0	1	4
Blood creatinine increased
subjects affected / exposed	2 / 49 (4.08%)	3 / 106 (2.83%)	1 / 18 (5.56%)	5 / 93 (5.38%)	2 / 43 (4.65%)
occurrences all number	2	3	1	6	3
Blood thyroid stimulating hormone increased
subjects affected / exposed	2 / 49 (4.08%)	0 / 106 (0.00%)	1 / 18 (5.56%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences all number	2	0	1	2	0
Lipase increased
subjects affected / exposed	2 / 49 (4.08%)	6 / 106 (5.66%)	0 / 18 (0.00%)	8 / 93 (8.60%)	2 / 43 (4.65%)
occurrences all number	2	6	0	9	2
Lymphocyte count decreased
subjects affected / exposed	2 / 49 (4.08%)	2 / 106 (1.89%)	1 / 18 (5.56%)	3 / 93 (3.23%)	3 / 43 (6.98%)
occurrences all number	3	3	1	5	3
Weight decreased
subjects affected / exposed	7 / 49 (14.29%)	18 / 106 (16.98%)	0 / 18 (0.00%)	15 / 93 (16.13%)	13 / 43 (30.23%)
occurrences all number	7	19	0	17	14
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 49 (2.04%)	3 / 106 (2.83%)	1 / 18 (5.56%)	0 / 93 (0.00%)	2 / 43 (4.65%)
occurrences all number	1	3	1	0	2
Cardiac disorders
Tachycardia
subjects affected / exposed	3 / 49 (6.12%)	4 / 106 (3.77%)	0 / 18 (0.00%)	5 / 93 (5.38%)	1 / 43 (2.33%)
occurrences all number	4	5	0	6	1
Nervous system disorders
Dizziness
subjects affected / exposed	7 / 49 (14.29%)	14 / 106 (13.21%)	1 / 18 (5.56%)	15 / 93 (16.13%)	3 / 43 (6.98%)
occurrences all number	7	14	1	18	3
Dizziness postural
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0
Dysgeusia
subjects affected / exposed	2 / 49 (4.08%)	10 / 106 (9.43%)	0 / 18 (0.00%)	2 / 93 (2.15%)	2 / 43 (4.65%)
occurrences all number	2	11	0	2	2
Headache
subjects affected / exposed	12 / 49 (24.49%)	16 / 106 (15.09%)	2 / 18 (11.11%)	14 / 93 (15.05%)	8 / 43 (18.60%)
occurrences all number	14	18	2	21	10
Hypoaesthesia
subjects affected / exposed	3 / 49 (6.12%)	2 / 106 (1.89%)	0 / 18 (0.00%)	1 / 93 (1.08%)	1 / 43 (2.33%)
occurrences all number	3	3	0	1	1
Peripheral motor neuropathy
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	3	1	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 49 (0.00%)	4 / 106 (3.77%)	1 / 18 (5.56%)	4 / 93 (4.30%)	2 / 43 (4.65%)
occurrences all number	0	4	1	4	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	8 / 49 (16.33%)	25 / 106 (23.58%)	2 / 18 (11.11%)	14 / 93 (15.05%)	6 / 43 (13.95%)
occurrences all number	11	34	2	16	7
Eye disorders
Vision blurred
subjects affected / exposed	3 / 49 (6.12%)	3 / 106 (2.83%)	0 / 18 (0.00%)	5 / 93 (5.38%)	1 / 43 (2.33%)
occurrences all number	3	4	0	5	1
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	1 / 18 (5.56%)	0 / 93 (0.00%)	2 / 43 (4.65%)
occurrences all number	1	1	1	0	2
Abdominal distension
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)	5 / 93 (5.38%)	2 / 43 (4.65%)
occurrences all number	1	1	0	5	2
Abdominal pain
subjects affected / exposed	5 / 49 (10.20%)	11 / 106 (10.38%)	2 / 18 (11.11%)	12 / 93 (12.90%)	6 / 43 (13.95%)
occurrences all number	7	15	2	14	6
Abdominal pain upper
subjects affected / exposed	3 / 49 (6.12%)	1 / 106 (0.94%)	0 / 18 (0.00%)	4 / 93 (4.30%)	2 / 43 (4.65%)
occurrences all number	3	1	0	4	2
Constipation
subjects affected / exposed	9 / 49 (18.37%)	33 / 106 (31.13%)	1 / 18 (5.56%)	26 / 93 (27.96%)	13 / 43 (30.23%)
occurrences all number	11	38	1	29	14
Diarrhoea
subjects affected / exposed	15 / 49 (30.61%)	32 / 106 (30.19%)	5 / 18 (27.78%)	24 / 93 (25.81%)	11 / 43 (25.58%)
occurrences all number	25	43	5	36	13
Dry mouth
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	2 / 18 (11.11%)	5 / 93 (5.38%)	0 / 43 (0.00%)
occurrences all number	1	1	2	6	0
Dyspepsia
subjects affected / exposed	3 / 49 (6.12%)	3 / 106 (2.83%)	1 / 18 (5.56%)	4 / 93 (4.30%)	1 / 43 (2.33%)
occurrences all number	3	4	1	4	1
Mouth ulceration
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0
Nausea
subjects affected / exposed	17 / 49 (34.69%)	45 / 106 (42.45%)	3 / 18 (16.67%)	27 / 93 (29.03%)	16 / 43 (37.21%)
occurrences all number	20	60	3	33	18
Stomatitis
subjects affected / exposed	1 / 49 (2.04%)	4 / 106 (3.77%)	2 / 18 (11.11%)	0 / 93 (0.00%)	3 / 43 (6.98%)
occurrences all number	3	4	2	0	3
Tongue dysplasia
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0
Vomiting
subjects affected / exposed	9 / 49 (18.37%)	26 / 106 (24.53%)	1 / 18 (5.56%)	20 / 93 (21.51%)	5 / 43 (11.63%)
occurrences all number	11	30	2	30	6
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 49 (0.00%)	6 / 106 (5.66%)	1 / 18 (5.56%)	3 / 93 (3.23%)	3 / 43 (6.98%)
occurrences all number	0	6	1	3	3
Dry skin
subjects affected / exposed	4 / 49 (8.16%)	6 / 106 (5.66%)	1 / 18 (5.56%)	8 / 93 (8.60%)	3 / 43 (6.98%)
occurrences all number	4	6	1	11	3
Hyperhidrosis
subjects affected / exposed	2 / 49 (4.08%)	2 / 106 (1.89%)	0 / 18 (0.00%)	1 / 93 (1.08%)	3 / 43 (6.98%)
occurrences all number	2	3	0	1	4
Night sweats
subjects affected / exposed	0 / 49 (0.00%)	1 / 106 (0.94%)	1 / 18 (5.56%)	3 / 93 (3.23%)	0 / 43 (0.00%)
occurrences all number	0	1	1	3	0
Pruritus
subjects affected / exposed	8 / 49 (16.33%)	11 / 106 (10.38%)	1 / 18 (5.56%)	22 / 93 (23.66%)	3 / 43 (6.98%)
occurrences all number	12	15	1	28	3
Rash
subjects affected / exposed	5 / 49 (10.20%)	17 / 106 (16.04%)	3 / 18 (16.67%)	15 / 93 (16.13%)	3 / 43 (6.98%)
occurrences all number	7	19	3	19	3
Rash maculo-papular
subjects affected / exposed	2 / 49 (4.08%)	2 / 106 (1.89%)	0 / 18 (0.00%)	9 / 93 (9.68%)	2 / 43 (4.65%)
occurrences all number	2	2	0	11	2
Rash pruritic
subjects affected / exposed	1 / 49 (2.04%)	4 / 106 (3.77%)	1 / 18 (5.56%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences all number	1	4	1	3	0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 49 (0.00%)	2 / 106 (1.89%)	1 / 18 (5.56%)	3 / 93 (3.23%)	0 / 43 (0.00%)
occurrences all number	0	2	1	4	0
Hypothyroidism
subjects affected / exposed	4 / 49 (8.16%)	4 / 106 (3.77%)	0 / 18 (0.00%)	9 / 93 (9.68%)	1 / 43 (2.33%)
occurrences all number	4	4	0	9	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	12 / 49 (24.49%)	11 / 106 (10.38%)	1 / 18 (5.56%)	15 / 93 (16.13%)	6 / 43 (13.95%)
occurrences all number	14	14	1	15	7
Back pain
subjects affected / exposed	10 / 49 (20.41%)	17 / 106 (16.04%)	1 / 18 (5.56%)	19 / 93 (20.43%)	8 / 43 (18.60%)
occurrences all number	11	18	1	20	8
Flank pain
subjects affected / exposed	0 / 49 (0.00%)	5 / 106 (4.72%)	1 / 18 (5.56%)	3 / 93 (3.23%)	2 / 43 (4.65%)
occurrences all number	0	5	1	3	2
Musculoskeletal chest pain
subjects affected / exposed	3 / 49 (6.12%)	7 / 106 (6.60%)	1 / 18 (5.56%)	4 / 93 (4.30%)	1 / 43 (2.33%)
occurrences all number	3	7	1	4	1
Musculoskeletal pain
subjects affected / exposed	8 / 49 (16.33%)	10 / 106 (9.43%)	1 / 18 (5.56%)	8 / 93 (8.60%)	5 / 43 (11.63%)
occurrences all number	8	11	1	8	5
Musculoskeletal stiffness
subjects affected / exposed	3 / 49 (6.12%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	3	0	0	0	0
Myalgia
subjects affected / exposed	4 / 49 (8.16%)	6 / 106 (5.66%)	1 / 18 (5.56%)	5 / 93 (5.38%)	5 / 43 (11.63%)
occurrences all number	5	6	1	5	5
Neck pain
subjects affected / exposed	1 / 49 (2.04%)	6 / 106 (5.66%)	1 / 18 (5.56%)	1 / 93 (1.08%)	0 / 43 (0.00%)
occurrences all number	1	6	1	1	0
Pain in extremity
subjects affected / exposed	7 / 49 (14.29%)	11 / 106 (10.38%)	0 / 18 (0.00%)	4 / 93 (4.30%)	3 / 43 (6.98%)
occurrences all number	8	13	0	5	3
Spinal pain
subjects affected / exposed	3 / 49 (6.12%)	0 / 106 (0.00%)	0 / 18 (0.00%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	3	0	0	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	1 / 18 (5.56%)	3 / 93 (3.23%)	0 / 43 (0.00%)
occurrences all number	2	2	1	4	0
Influenza
subjects affected / exposed	2 / 49 (4.08%)	0 / 106 (0.00%)	0 / 18 (0.00%)	1 / 93 (1.08%)	3 / 43 (6.98%)
occurrences all number	3	0	0	2	3
Laryngitis
subjects affected / exposed	0 / 49 (0.00%)	0 / 106 (0.00%)	1 / 18 (5.56%)	0 / 93 (0.00%)	0 / 43 (0.00%)
occurrences all number	0	0	1	0	0
Nasopharyngitis
subjects affected / exposed	2 / 49 (4.08%)	6 / 106 (5.66%)	0 / 18 (0.00%)	2 / 93 (2.15%)	1 / 43 (2.33%)
occurrences all number	2	7	0	2	1
Pneumonia
subjects affected / exposed	3 / 49 (6.12%)	6 / 106 (5.66%)	0 / 18 (0.00%)	3 / 93 (3.23%)	2 / 43 (4.65%)
occurrences all number	4	6	0	3	3
Upper respiratory tract infection
subjects affected / exposed	3 / 49 (6.12%)	4 / 106 (3.77%)	1 / 18 (5.56%)	1 / 93 (1.08%)	4 / 43 (9.30%)
occurrences all number	4	5	1	2	4
Urinary tract infection
subjects affected / exposed	7 / 49 (14.29%)	2 / 106 (1.89%)	0 / 18 (0.00%)	3 / 93 (3.23%)	1 / 43 (2.33%)
occurrences all number	8	2	0	6	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	18 / 49 (36.73%)	39 / 106 (36.79%)	5 / 18 (27.78%)	24 / 93 (25.81%)	15 / 43 (34.88%)
occurrences all number	22	44	5	30	17
Dehydration
subjects affected / exposed	1 / 49 (2.04%)	6 / 106 (5.66%)	0 / 18 (0.00%)	5 / 93 (5.38%)	4 / 43 (9.30%)
occurrences all number	1	6	0	5	4
Hyperglycaemia
subjects affected / exposed	1 / 49 (2.04%)	3 / 106 (2.83%)	1 / 18 (5.56%)	4 / 93 (4.30%)	3 / 43 (6.98%)
occurrences all number	4	3	1	5	3
Hyperkalaemia
subjects affected / exposed	1 / 49 (2.04%)	1 / 106 (0.94%)	0 / 18 (0.00%)	6 / 93 (6.45%)	0 / 43 (0.00%)
occurrences all number	1	1	0	7	0
Hypocalcaemia
subjects affected / exposed	3 / 49 (6.12%)	2 / 106 (1.89%)	0 / 18 (0.00%)	2 / 93 (2.15%)	0 / 43 (0.00%)
occurrences all number	5	2	0	3	0
Hypokalaemia
subjects affected / exposed	4 / 49 (8.16%)	6 / 106 (5.66%)	1 / 18 (5.56%)	7 / 93 (7.53%)	2 / 43 (4.65%)
occurrences all number	5	8	1	8	2
Hypomagnesaemia
subjects affected / exposed	5 / 49 (10.20%)	8 / 106 (7.55%)	0 / 18 (0.00%)	11 / 93 (11.83%)	1 / 43 (2.33%)
occurrences all number	5	9	0	12	1
Hyponatraemia
subjects affected / exposed	6 / 49 (12.24%)	10 / 106 (9.43%)	1 / 18 (5.56%)	13 / 93 (13.98%)	2 / 43 (4.65%)
occurrences all number	6	13	1	18	2
Hypophosphataemia
subjects affected / exposed	3 / 49 (6.12%)	9 / 106 (8.49%)	0 / 18 (0.00%)	4 / 93 (4.30%)	1 / 43 (2.33%)
occurrences all number	3	14	0	6	1

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Were there any global substantial amendments to the protocol? Yes

08 Apr 2016

Statistical study design update

27 Jul 2016

Inclusion/exclusion criteria update

21 Sep 2016

Management Algorithms for Immuno-Oncology Agents update

13 Oct 2016

Inclusion/exclusion criteria update

16 Feb 2017

Study design simplification and study tracks re-arrangement

12 Apr 2018

Study design changes

22 Apr 2019

Adjustment of Follow-up period timelines

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.

This study was terminated early by sponsor for reasons unrelated to safety.. 14 of the 295 participants initially received a treatment and then were re-randomized to a different, non-concomitant second treatment

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Clinical Trial Results:
A Phase 2, Fast Real-time Assessment of Combination Therapies in Immuno-ONcology Study in Subjects with Advanced Non-small Cell Lung Cancer (FRACTION-Lung)

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Subject disposition

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Baseline characteristics

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End points

Primary: Objective Response Rate (ORR)

Primary: Objective Response Rate (ORR)

Primary: Duration of Response (DOR)

Primary: Duration of Response (DOR)

Primary: Progression Free Survival Rate (PFSR) at 24 Weeks

Primary: Progression Free Survival Rate (PFSR) at 24 Weeks

Secondary: Percentage of Subjects Experiencing Adverse Events (AEs)

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Secondary: Percentage of Subjects Experiencing Serious Adverse Events (SAEs)

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Clinical trials

Clinical Trial Results: A Phase 2, Fast Real-time Assessment of Combination Therapies in Immuno-ONcology Study in Subjects with Advanced Non-small Cell Lung Cancer (FRACTION-Lung)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Objective Response Rate (ORR)

Primary: Objective Response Rate (ORR)

Primary: Duration of Response (DOR)

Primary: Duration of Response (DOR)

Primary: Progression Free Survival Rate (PFSR) at 24 Weeks

Primary: Progression Free Survival Rate (PFSR) at 24 Weeks

Secondary: Percentage of Subjects Experiencing Adverse Events (AEs)

Secondary: Percentage of Subjects Experiencing Adverse Events (AEs)

Secondary: Percentage of Subjects Experiencing Serious Adverse Events (SAEs)

Secondary: Percentage of Subjects Experiencing Serious Adverse Events (SAEs)

Secondary: Percentage of Subjects Experiencing Adverse Events (AEs) Leading to Discontinuation

Secondary: Percentage of Subjects Experiencing Adverse Events (AEs) Leading to Discontinuation

Secondary: Percentage of Subjects Experiencing Death

Secondary: Percentage of Subjects Experiencing Death

Secondary: Number of Subjects Experiencing Laboratory Abnormalities in Hepatic Tests

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Secondary: Number of Subjects Experiencing Laboratory Abnormalities in Thyroid Tests

Secondary: Number of Subjects Experiencing Laboratory Abnormalities in Thyroid Tests

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Phase 2, Fast Real-time Assessment of Combination Therapies in Immuno-ONcology Study in Subjects with Advanced Non-small Cell Lung Cancer (FRACTION-Lung)