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Clinical Trial Results:
A Phase 2 Study of Nivolumab in Combination with Either Rucaparib, Docetaxel, or Enzalutamide in Men with Castration-resistant Metastatic Prostate Cancer (CheckMate 9KD: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 9KD)

Summary
EudraCT number	2017-001626-17
Trial protocol	DE ES FR
Global end of trial date	10 Jan 2025

Results information
Results version number	v1(current)
This version publication date	24 Jan 2026
First version publication date	24 Jan 2026
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

CA209-9KD

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Bristol-Myers Squibb

Sponsor organisation address

Chausse de la Hulpe 185, Brussels, Belgium, 1170

Public contact

Global Submission Management, Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com

Scientific contact

Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, mg-gsm-ct@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

06 Feb 2025

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

10 Jan 2025

Was the trial ended prematurely?

Main objective of the trial

Evaluate efficacy of nivolumab combined with either rucaparib, docetaxel, or enzalutamide in participants with Castration-resistant Metastatic Prostrate Cancer

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 participants were followed.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Dec 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 17

Country: Number of subjects enrolled

Australia: 24

Country: Number of subjects enrolled

Brazil: 38

Country: Number of subjects enrolled

Canada: 14

Country: Number of subjects enrolled

Chile: 16

Country: Number of subjects enrolled

Colombia: 2

Country: Number of subjects enrolled

France: 31

Country: Number of subjects enrolled

Germany: 32

Country: Number of subjects enrolled

Mexico: 19

Country: Number of subjects enrolled

Spain: 27

Country: Number of subjects enrolled

United States: 72

Worldwide total number of subjects

292

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

192

85 years and over

Subject disposition

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Recruitment details

Screening details

292 participants treated

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

Yes

Arm A1

Arm description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have at lease 1 but no more than 2 prior chemotherapy regimens

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

480 mg every four weeks

Arm A2

Arm description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have not received prior chemotherapy regimen

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

480 mg every four weeks

Arm B

Arm description

Nivolumab 360 mg IV Q3W + Docetaxel 75 mg/m2 IV Q3W + Prednisone 5 mg PO BID

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

360 mg every three weeks

Arm C

Arm description

Nivolumab 480 mg IV Q4W + Enzalutamide 160 mg PO QD

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

480 mg every four weeks

Number of subjects in period 1	Arm A1	Arm A2	Arm B	Arm C
Started	88	71	84	49
Completed	0	3	1	0
Not completed	88	68	83	49
Adverse event, serious fatal	2	1	1	-
Participant withdrew consent	1	-	1	1
Maximum clinical benefit	-	-	1	-
Participant no longer meets study criteria	-	-	1	-
Adverse Event unrelated to Study Drug	4	4	6	4
Other reasons	-	5	1	1
Study Drug Toxicity	12	8	14	-
Poor/non-compliance	-	1	-	-
Disease Progression	65	46	54	42
Participant request to discontinue study treatment	4	3	3	1
Administrative reason by sponsor	-	-	1	-

Baseline characteristics

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Reporting group title

Arm A1

Reporting group description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have at lease 1 but no more than 2 prior chemotherapy regimens

Reporting group title

Arm A2

Reporting group description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have not received prior chemotherapy regimen

Reporting group title

Arm B

Reporting group description

Nivolumab 360 mg IV Q3W + Docetaxel 75 mg/m2 IV Q3W + Prednisone 5 mg PO BID

Reporting group title

Arm C

Reporting group description

Nivolumab 480 mg IV Q4W + Enzalutamide 160 mg PO QD

Reporting group values	Arm A1	Arm A2	Arm B	Arm C	Total
Number of subjects	88	71	84	49	292
Age categorical
Units:
Age Continuous
Units: years
arithmetic mean (standard deviation)	66.6 ( 8.3 )	70.7 ( 9.7 )	70.3 ( 7.6 )	69.8 ( 8.0 )	-
Sex: Female, Male
Units: Participants
Female	0	0	0	0	0
Male	88	71	84	49	292
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0
Asian	2	1	1	0	4
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	4	1	8	2	15
White	72	64	70	42	248
More than one race	0	0	0	0	0
Unknown or Not Reported	10	5	5	5	25

End points

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Reporting group title

Arm A1

Reporting group description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have at lease 1 but no more than 2 prior chemotherapy regimens

Reporting group title

Arm A2

Reporting group description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have not received prior chemotherapy regimen

Reporting group title

Arm B

Reporting group description

Nivolumab 360 mg IV Q3W + Docetaxel 75 mg/m2 IV Q3W + Prednisone 5 mg PO BID

Reporting group title

Arm C

Reporting group description

Nivolumab 480 mg IV Q4W + Enzalutamide 160 mg PO QD

Primary: Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3)

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End point title

Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) ^[1]

End point description

Objective response rate per prostate cancer clinical trials working group 3 (ORR-PCWG3) for target lesions and assessed by MRI is the percentage of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among treated participants who have measurable disease. HRD+ N=Number of subjects analyzed in HRD+ subgroup

End point type

Primary

End point timeframe

Up to approximately 36 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: Only summary statistics planned for this endpoint

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	58 ^[2]	39 ^[3]	45 ^[4]	18 ^[5]
Units: Percentage of participants
number (confidence interval 95%)
Overall	10.3 (3.9 to 21.2)	15.4 (5.9 to 30.5)	40.0 (25.7 to 55.7)	11.1 (1.4 to 34.7)
Homologous Recombination Deficiency (HRD+)	17.2 (5.8 to 35.8)	25.0 (8.7 to 49.1)	36.8 (16.3 to 61.6)	20.0 (0.5 to 71.6)

Notes
[2] - HRD+ N= 29
[3] - HRD+ N= 20
[4] - HRD+ N= 19
[5] - HRD+ N= 5

No statistical analyses for this end point

Primary: Prostate-Specific Antigen Response Rate (RR-PSA)

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End point title

Prostate-Specific Antigen Response Rate (RR-PSA) ^[6]

End point description

Prostate-specific antigen response rate (RR-PSA) is the percentage of treated participants with a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result. HRD+ N=Number of subjects analyzed in HRD+ subgroup

End point type

Primary

End point timeframe

Up to approximately 36 months

Notes
[6] - 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: Only summary statistics planned for this endpoint

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	84 ^[7]	66 ^[8]	81 ^[9]	44 ^[10]
Units: Percentage of participants
number (confidence interval 95%)
Overall	11.9 (5.9 to 20.8)	27.3 (17.0 to 39.6)	46.9 (35.7 to 58.3)	34.1 (20.5 to 49.9)
Homologous Recombination Deficiency (HRD+)	18.2 (8.2 to 32.7)	41.9 (24.5 to 60.9)	50.0 (32.4 to 67.6)	50.0 (18.7 to 81.3)

Notes
[7] - HRD+ N= 44
[8] - HRD+ N= 31
[9] - HRD+ N= 34
[10] - HRD+ N= 10

No statistical analyses for this end point

Secondary: Radiographic Progression-Free Survival (rPFS)

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End point title

Radiographic Progression-Free Survival (rPFS)

End point description

Radiographic progress-free survival (rPFS) is the time between treatment initiation and the first date of documented progression or death due to any cause, whichever occurs first assessed by the investigator per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) 99999=NA HRD+ N=Number of subjects analyzed in HRD+ subgroup

End point type

Secondary

End point timeframe

Up to approximately 84 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	88 ^[11]	71 ^[12]	84 ^[13]	49 ^[14]
Units: Months
median (confidence interval 95%)
Overall	4.60 (3.68 to 5.72)	8.15 (5.59 to 10.97)	9.20 (8.25 to 11.47)	5.75 (3.81 to 9.33)
Homologous Recombination Deficiency (HRD+)	5.59 (3.68 to 8.08)	11.01 (6.74 to 12.02)	10.45 (8.44 to 12.88)	8.48 (3.78 to 99999)

Notes
[11] - HRD+ N= 45
[12] - HRD+ N= 34
[13] - HRD+ N= 35
[14] - HRD+ N= 12

No statistical analyses for this end point

Secondary: Time to Response per Prostate Cancer Clinical Trials Working Group 3 (TTR-PCWG3)

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End point title

Time to Response per Prostate Cancer Clinical Trials Working Group 3 (TTR-PCWG3)

End point description

Time to response per prostate cancer clinical trials working group 3 (TTR-PCWG3) is the time from treatment initiation to the date of the first documented complete response (CR) or partial response (PR) per Prostate Cancer Clinical Trials Working Group 3 (PCWG3). HRD+ N=Number of subjects analyzed in HRD+ subgroup

End point type

Secondary

End point timeframe

Up to approximately 84 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	7 ^[15]	6 ^[16]	21 ^[17]	2 ^[18]
Units: Months
median (full range (min-max))
Overall	1.94 (1.6 to 5.1)	1.95 (1.8 to 11.0)	1.94 (1.6 to 8.3)	1.9 (1.9 to 1.9)
Homologous Recombination Deficiency (HRD+)	2.76 (1.6 to 5.1)	2.07 (1.8 to 11.0)	2.04 (1.8 to 8.3)	1.9 (1.9 to 1.9)

Notes
[15] - HRD+ N+ 6
[16] - HRD+ N= 5
[17] - HRD+ N= 9
[18] - HRD+ N= 1

No statistical analyses for this end point

Secondary: Duration of Response per Prostate Cancer Clinical Trials Working Group 3 (DOR-PCWG3)

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End point title

Duration of Response per Prostate Cancer Clinical Trials Working Group 3 (DOR-PCWG3)

End point description

Duration of response per prostate cancer clinical trials working group 3 (DOR-PCWG3) is the time between the date of first response (complete response/partial response per PCWG3) to the date of first documented radiographic progression per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) or death due to any cause. 99999=NA HRD+ N=Number of subjects analyzed in HRD+ subgroup

End point type

Secondary

End point timeframe

Up to approximately 84 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	7 ^[19]	6 ^[20]	21 ^[21]	2 ^[22]
Units: Months
median (confidence interval 95%)
Overall	99999 (3.45 to 99999)	7.10 (3.78 to 99999)	7.21 (6.47 to 12.35)	99999 (9.23 to 99999)
Homologous Recombination Deficiency (HRD+)	99999 (3.45 to 99999)	7.10 (3.78 to 99999)	7.43 (6.44 to 13.86)	99999 (99999 to 99999)

Notes
[19] - HRD+ N= 6
[20] - HRD+ N= 5
[21] - HRD+ N= 9
[22] - HRD+ N= 1

No statistical analyses for this end point

Secondary: Prostate-Specific Antigen Time to Progression (TTP-PSA)

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End point title

Prostate-Specific Antigen Time to Progression (TTP-PSA)

End point description

Prostate-specific antigen time to progression (TTP-PSA) is the time between treatment initiation to the date of PSA progression per prostate cancer clinical trials working group 3 (PCWG3). HRD+ N=Number of subjects analyzed in HRD+ subgroup

End point type

Secondary

End point timeframe

Up to approximately 84 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	85 ^[23]	66 ^[24]	81 ^[25]	44 ^[26]
Units: Months
median (confidence interval 95%)
Overall	3.78 (2.83 to 6.47)	3.45 (2.83 to 6.21)	8.67 (7.16 to 10.35)	3.09 (2.79 to 6.37)
Homologous Recombination Deficiency (HRD+)	6.47 (3.78 to 9.63)	10.25 (4.63 to 13.77)	8.64 (7.16 to 10.58)	5.55 (2.73 to 8.28)

Notes
[23] - HRD+ N= 44
[24] - HRD+ N= 32
[25] - HRD+ N= 34
[26] - HRD+ N= 10

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

Overall Survival (OS) is the time between treatment initiation and the date of death from any cause. For participants who are alive, their survival time will be censored at the last date that they were known to be alive. OS will be censored for participants at the date of treatment initiation if they had no follow-up. HRD+ N=Number of subjects analyzed in HRD+ subgroup

End point type

Secondary

End point timeframe

Up to approximately 84 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	88 ^[27]	71 ^[28]	84 ^[29]	49 ^[30]
Units: Months
median (confidence interval 95%)
Overall	13.96 (10.35 to 15.77)	20.24 (13.54 to 22.90)	18.17 (15.15 to 25.49)	17.41 (12.98 to 24.15)
Homologous Recombination Deficiency (HRD+)	15.15 (11.40 to 18.20)	23.00 (13.54 to 29.27)	19.35 (13.54 to 27.20)	24.97 (9.10 to 45.50)

Notes
[27] - HRD+ N= 45
[28] - HRD+ N= 34
[29] - HRD+ N= 35
[30] - HRD+ N= 12

No statistical analyses for this end point

Secondary: Number of Participants with Adverse Events (AEs)

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End point title

Number of Participants with Adverse Events (AEs)

End point description

Number of Participants with any grade adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and immune-mediated AEs using the Common Toxicity Criteria Grade for Adverse Events (CTCAE V4)

End point type

Secondary

End point timeframe

From first dose to up to 30 days post last dose (Up to 82 months)

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	88	71	84	49
Units: Participants
Adverse Events (AEs)	88	71	83	49
Serious Adverse Events (SAEs)	49	37	41	20
AEs leading to discontinuation	47	31	37	17
Immune-mediated AEs (Pneumonitis)	1	2	9	0
Immune-mediated AEs (Diarrhea/Colitis)	3	4	2	0
Immune-mediated AEs (Hepatitis)	8	6	1	2
Immune-mediated AEs (Nephritis/Renal Dysfunction)	0	3	0	0
Immune-mediated AEs (Rash)	6	5	7	10
Immune-mediated AEs (Hypersensitivity)	0	0	0	3
Immune-mediated AEs (Adrenal insufficiency)	1	0	0	0
Immune-mediated AEs (Hypothyroidism/Thyroiditis)	7	6	3	5
Immune-mediated AEs (Hyperthyroidism)	2	1	2	0
Immune-mediated AEs (Hypophysitis)	0	0	1	0
Immune-mediated AEs (Diabetes Mellitus)	0	1	0	1

No statistical analyses for this end point

Secondary: Number of Participants who Died

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End point title

Number of Participants who Died

End point description

Number of participants who died due to any cause.

End point type

Secondary

End point timeframe

Up to 84 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	88	71	84	49
Units: Participants	79	66	76	47

No statistical analyses for this end point

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

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End point title

Number of Participants with Laboratory Abnormalities in Specific Liver Tests

End point description

Number of participants with laboratory abnormalities in specific liver tests based on SI conventional units to assess the overall safety and tolerability of BMS-986213 in combination with chemotherapy vs. Nivolumab in combination with chemotherapy. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: - ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN - Total bilirubin > 2 x ULN - ALP > 1.5 x ULN - Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN - Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 1.5 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

End point type

Secondary

End point timeframe

From first dose to up to 30 days post last dose (up to 82 months)

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	88	69	84	48
Units: Participants
ALT or AST > 3xULN	19	23	6	4
ALT or AST > 5xULN	11	15	3	3
ALT or AST > 10xULN	2	5	1	0
ALT or AST > 20xULN	0	1	1	0
TOTAL BILIRUBIN > 2xULN	3	1	1	0
ALP > 1.5xULN	49	34	35	22
ALT/AST>3xULN Bilirubin>1.5xULN within 1 day	3	1	0	1
ALT/AST> 3xULN Bilirubin>1.5xULN within 30 days	4	1	0	1
ALT/AST>3xULN Bilirubin>2xULN within 1 day	2	1	0	0
ALT/AST>3xULN Bilirubin>2xULN within 30 days	2	1	0	0

No statistical analyses for this end point

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

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End point title

Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

End point description

Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: - TSH value > ULN and - with baseline TSH value <= ULN - with at least one FT3/FT4 test value < LLN within 2-week window after the abnormal TSH test - with all FT3/FT4 test values >= LLN within 2-week window after the abnormal TSH test - with FT3/FT4 missing within 2-week window after the abnormal TSH test. - TSH < LLN and - with baseline TSH value >= LLN - with at least one FT3/FT4 test value > ULN within 2-week window after the abnormal TSH test - with all FT3/FT4 test values <= ULN within 2-week window after the abnormal TSH test - with FT3/FT4 missing within 2-week window after the abnormal TSH test

End point type

Secondary

End point timeframe

From first dose to up to 30 days post last dose (Up to 82 months)

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	88	71	84	49
Units: Participants
TSH > ULN	23	17	12	17
TSH > ULN with TSH <= ULN at baseline	18	12	7	12
TSH>ULN with at least one FT3/FT4 test value<LLN	10	6	7	5
TSH>ULN with all other FT3/FT4 test values>= LLN	11	9	3	9
TSH>ULN with FT3/FT4 test missing	2	2	2	3
TSH < LLN	17	12	25	8
TSH < LLN with TSH >= LLN at baseline	14	11	19	8
TSH<LLN with at least one FT3/FT4 test value>ULN	6	5	2	7
TSH<LLN with all other FT3/FT4 test values<= ULN	8	4	11	0
TSH < LLN with FT3/FT4 test missing	3	3	12	1

No statistical analyses for this end point

Secondary: Number of Participants with Laboratory Values Change from Baseline

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End point title

Number of Participants with Laboratory Values Change from Baseline

End point description

Number of participants changed from baseline in laboratory values of worst toxicity grade (grade 0= wnl, grade 1= mild, grade 2= moderate, grade 3= severe) based on US conventional units by cohort. 99999=NA

End point type

Secondary

End point timeframe

From first dose to up to 30 days post last dose (Up to 82 months)

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	88	71	84	49
Units: Participants
Hemoglobin Grade 0	23	21	30	8
Hemoglobin Grade 1	38	28	23	13
Hemoglobin Grade 2	8	3	2	2
Platelet Grade 0	34	32	10	13
Platelet Grade 1	4	1	0	0
Leukocytes Grade 0	39	35	30	13
Leukocytes Grade 1	10	6	3	3
Leukocytes Grade 2	1	0	1	99999
Lymphocytes Grade 0	24	30	28	14
Lymphocytes Grade 1	11	8	1	2
Lymphocytes Grade 2	3	3	6	3
Lymphocytes Grade 3	1	0	0	99999
Neutrophil Grade 0	35	26	38	7
Neutrophil Grade 1	3	4	1	99999
Neutrophil Grade 2	1	99999	99999	1
Alkaline Phosphatase Grade 0	25	34	13	8
Alkaline Phosphatase Grade 1	14	4	13	6
Alkaline Phosphatase Grade 2	9	1	3	0
Alkaline Phosphatase Grade 3	1	3	0	0
Aspartate Aminotransferase Grade 0	52	49	16	9
Aspartate Aminotransferase Grade 1	5	4	6	4
Alanine Aminotransferase Grade 0	48	48	13	4
Alanine Aminotransferase Grade 1	4	3	3	1
Bilirubin Grade 0	16	12	2	3
Bilirubin Grade 1	1	99999	99999	0
Creatinine Grade 0	31	30	13	3
Creatinine Grade 1	7	5	5	2

No statistical analyses for this end point

Post-hoc: Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) - Extended Collection

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End point title

Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) - Extended Collection

End point description

End point type

Post-hoc

End point timeframe

Up to approximately 82 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	58 ^[31]	39 ^[32]	45 ^[33]	18 ^[34]
Units: Percentage of participants
number (confidence interval 95%)
Overall	12.1 (5.0 to 23.3)	15.4 (5.9 to 30.5)	40.0 (25.7 to 55.7)	11.1 (1.4 to 34.7)
Homologous Recombination Deficiency (HRD+)	20.7 (8.0 to 39.7)	25.0 (8.7 to 49.1)	36.8 (16.3 to 61.6)	20.0 (0.5 to 71.6)

Notes
[31] - HRD+ N= 29
[32] - HRD+ N= 20
[33] - HRD+ N= 19
[34] - HRD+ N= 5

No statistical analyses for this end point

Post-hoc: Prostate-Specific Antigen Response Rate (RR-PSA) - Extended Collection

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End point title

Prostate-Specific Antigen Response Rate (RR-PSA) - Extended Collection

End point description

End point type

Post-hoc

End point timeframe

Up to approximately 82 months

End point values	Arm A1	Arm A2	Arm B	Arm C
Number of subjects analysed	85 ^[35]	66 ^[36]	81 ^[37]	44 ^[38]
Units: Percentage of participants
number (confidence interval 95%)
Overall	11.8 (5.8 to 20.6)	28.8 (18.3 to 41.3)	46.9 (35.7 to 58.3)	34.1 (20.5 to 49.9)
Homologous Recombination Deficiency (HRD+)	18.2 (8.2 to 32.7)	43.8 (26.4 to 62.3)	50.0 (32.4 to 67.6)	50.0 (18.7 to 81.3)

Notes
[35] - HRD+ N= 44
[36] - HRD+ N= 32
[37] - HRD+ N= 34
[38] - HRD+ N= 10

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 84 months). SAEs and Other AEs were assessed from first dose to 100 days post the last dose (up to approximately 84 months).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.1

Reporting group title

Arm A1

Reporting group description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have at lease 1 but no more than 2 prior chemotherapy regimens

Reporting group title

Arm C

Reporting group description

Nivolumab 480 mg IV Q4W + Enzalutamide 160 mg PO QD

Reporting group title

Arm B

Reporting group description

Nivolumab 360 mg IV Q3W + Docetaxel 75 mg/m2 IV Q3W + Prednisone 5 mg PO BID

Reporting group title

Arm A2

Reporting group description

Nivolumab 480 mg IV Q4W + Rucaparib 600 mg PO BID for participants who have not received prior chemotherapy regimen

Serious adverse events	Arm A1	Arm C	Arm B	Arm A2
Total subjects affected by serious adverse events
subjects affected / exposed	53 / 88 (60.23%)	25 / 49 (51.02%)	50 / 84 (59.52%)	45 / 71 (63.38%)
number of deaths (all causes)	79	47	76	66
number of deaths resulting from adverse events	21	8	17	17
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cancer pain
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colon neoplasm
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Head and neck cancer
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Malignant neoplasm progression
subjects affected / exposed	14 / 88 (15.91%)	7 / 49 (14.29%)	8 / 84 (9.52%)	9 / 71 (12.68%)
occurrences causally related to treatment / all	0 / 14	0 / 7	0 / 8	0 / 9
deaths causally related to treatment / all	0 / 14	0 / 6	0 / 7	0 / 9
Metastases to bone
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 88 (1.14%)	1 / 49 (2.04%)	0 / 84 (0.00%)	3 / 71 (4.23%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 3
Second primary malignancy
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Peripheral artery thrombosis
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphatic fistula
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphoedema
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	2 / 84 (2.38%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Fatigue
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	1 / 84 (1.19%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	2 / 2	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	2 / 88 (2.27%)	1 / 49 (2.04%)	1 / 84 (1.19%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	2 / 84 (2.38%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Malaise
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	3 / 88 (3.41%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Immune system disorders
Sarcoidosis
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Testicular mass
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Aspiration
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epiglottic oedema
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 88 (1.14%)	1 / 49 (2.04%)	1 / 84 (1.19%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Pleural effusion
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	4 / 84 (4.76%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	8 / 8	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Productive cough
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated lung disease
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Confusional state
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hallucination
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abnormal behaviour
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device occlusion
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 88 (1.14%)	1 / 49 (2.04%)	1 / 84 (1.19%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	1 / 1	1 / 1	1 / 1	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	3 / 71 (4.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	2 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood bilirubin increased
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Electrocardiogram T wave inversion
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General physical condition abnormal
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Liver function test increased
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Ureteric anastomosis complication
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pelvic fracture
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Limb injury
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infusion related reaction
subjects affected / exposed	0 / 88 (0.00%)	2 / 49 (4.08%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular anastomosis aneurysm
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Angina pectoris
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Cardiac failure
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Presyncope
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Basal ganglia infarction
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	1 / 88 (1.14%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
Hyperaesthesia
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorder
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	0 / 84 (0.00%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Trigeminal neuralgia
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Disseminated intravascular coagulation
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	1 / 84 (1.19%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Febrile neutropenia
subjects affected / exposed	4 / 88 (4.55%)	0 / 49 (0.00%)	4 / 84 (4.76%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	3 / 4	0 / 0	4 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	8 / 88 (9.09%)	2 / 49 (4.08%)	0 / 84 (0.00%)	4 / 71 (5.63%)
occurrences causally related to treatment / all	6 / 8	1 / 2	0 / 0	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	4 / 88 (4.55%)	0 / 49 (0.00%)	4 / 84 (4.76%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	4 / 4	0 / 0	3 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo positional
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertigo
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	3 / 88 (3.41%)	0 / 49 (0.00%)	3 / 84 (3.57%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Faecaloma
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Haematochezia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	3 / 88 (3.41%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	2 / 3	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated enterocolitis
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileus paralytic
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Hepatitis
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic cytolysis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Drug-induced liver injury
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune hepatitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Cutaneous sarcoidosis
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash
subjects affected / exposed	0 / 88 (0.00%)	2 / 49 (4.08%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash maculo-papular
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rash morbilliform
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Bladder obstruction
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	7 / 88 (7.95%)	1 / 49 (2.04%)	1 / 84 (1.19%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	4 / 7	0 / 1	0 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune nephritis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	1 / 84 (1.19%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune-mediated nephritis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Proteinuria
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ureteric compression
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Urinoma
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ureteric obstruction
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthralgia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	2 / 84 (2.38%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	3 / 88 (3.41%)	2 / 49 (4.08%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	3 / 71 (4.23%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myositis
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periarthritis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal pain
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Biliary sepsis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis orbital
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Catheter site cellulitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	2 / 84 (2.38%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
Sepsis
subjects affected / exposed	2 / 88 (2.27%)	1 / 49 (2.04%)	3 / 84 (3.57%)	4 / 71 (5.63%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Rectal abscess
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary sepsis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Pneumonia
subjects affected / exposed	2 / 88 (2.27%)	2 / 49 (4.08%)	6 / 84 (7.14%)	9 / 71 (12.68%)
occurrences causally related to treatment / all	0 / 4	0 / 2	4 / 6	1 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	2 / 3	0 / 2
Neutropenic infection
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinusitis
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	1 / 84 (1.19%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	2 / 88 (2.27%)	1 / 49 (2.04%)	1 / 84 (1.19%)	3 / 71 (4.23%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	1 / 84 (1.19%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	3 / 88 (3.41%)	0 / 49 (0.00%)	2 / 84 (2.38%)	2 / 71 (2.82%)
occurrences causally related to treatment / all	1 / 3	0 / 0	1 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic metabolic decompensation
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	7 / 7	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypocalcaemia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	2 / 84 (2.38%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypophosphataemia
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	0 / 84 (0.00%)	1 / 71 (1.41%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Arm A1	Arm C	Arm B	Arm A2
Total subjects affected by non serious adverse events
subjects affected / exposed	87 / 88 (98.86%)	48 / 49 (97.96%)	83 / 84 (98.81%)	70 / 71 (98.59%)
Vascular disorders
Hypertension
subjects affected / exposed	5 / 88 (5.68%)	4 / 49 (8.16%)	5 / 84 (5.95%)	3 / 71 (4.23%)
occurrences all number	6	4	6	3
Hypotension
subjects affected / exposed	7 / 88 (7.95%)	1 / 49 (2.04%)	4 / 84 (4.76%)	6 / 71 (8.45%)
occurrences all number	8	1	8	7
General disorders and administration site conditions
Asthenia
subjects affected / exposed	24 / 88 (27.27%)	11 / 49 (22.45%)	17 / 84 (20.24%)	12 / 71 (16.90%)
occurrences all number	32	13	26	13
Chills
subjects affected / exposed	4 / 88 (4.55%)	1 / 49 (2.04%)	9 / 84 (10.71%)	6 / 71 (8.45%)
occurrences all number	4	1	10	6
Fatigue
subjects affected / exposed	36 / 88 (40.91%)	21 / 49 (42.86%)	41 / 84 (48.81%)	26 / 71 (36.62%)
occurrences all number	44	27	55	35
Mucosal inflammation
subjects affected / exposed	8 / 88 (9.09%)	1 / 49 (2.04%)	6 / 84 (7.14%)	1 / 71 (1.41%)
occurrences all number	9	1	12	1
Oedema peripheral
subjects affected / exposed	17 / 88 (19.32%)	10 / 49 (20.41%)	20 / 84 (23.81%)	15 / 71 (21.13%)
occurrences all number	19	12	25	17
Pain
subjects affected / exposed	6 / 88 (6.82%)	7 / 49 (14.29%)	3 / 84 (3.57%)	2 / 71 (2.82%)
occurrences all number	7	7	5	2
Pyrexia
subjects affected / exposed	15 / 88 (17.05%)	4 / 49 (8.16%)	13 / 84 (15.48%)	7 / 71 (9.86%)
occurrences all number	16	4	14	7
Respiratory, thoracic and mediastinal disorders
Pneumonitis
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	8 / 84 (9.52%)	2 / 71 (2.82%)
occurrences all number	0	0	8	2
Epistaxis
subjects affected / exposed	1 / 88 (1.14%)	2 / 49 (4.08%)	6 / 84 (7.14%)	0 / 71 (0.00%)
occurrences all number	1	2	6	0
Dyspnoea exertional
subjects affected / exposed	4 / 88 (4.55%)	1 / 49 (2.04%)	5 / 84 (5.95%)	0 / 71 (0.00%)
occurrences all number	4	1	5	0
Dyspnoea
subjects affected / exposed	13 / 88 (14.77%)	4 / 49 (8.16%)	20 / 84 (23.81%)	9 / 71 (12.68%)
occurrences all number	15	4	24	9
Cough
subjects affected / exposed	15 / 88 (17.05%)	2 / 49 (4.08%)	21 / 84 (25.00%)	11 / 71 (15.49%)
occurrences all number	15	2	25	12
Psychiatric disorders
Depression
subjects affected / exposed	2 / 88 (2.27%)	4 / 49 (8.16%)	2 / 84 (2.38%)	6 / 71 (8.45%)
occurrences all number	2	4	2	6
Insomnia
subjects affected / exposed	8 / 88 (9.09%)	8 / 49 (16.33%)	9 / 84 (10.71%)	6 / 71 (8.45%)
occurrences all number	8	9	10	8
Investigations
Weight decreased
subjects affected / exposed	9 / 88 (10.23%)	5 / 49 (10.20%)	6 / 84 (7.14%)	7 / 71 (9.86%)
occurrences all number	9	6	6	7
Transaminases increased
subjects affected / exposed	3 / 88 (3.41%)	1 / 49 (2.04%)	2 / 84 (2.38%)	4 / 71 (5.63%)
occurrences all number	3	1	2	4
Platelet count decreased
subjects affected / exposed	4 / 88 (4.55%)	1 / 49 (2.04%)	0 / 84 (0.00%)	6 / 71 (8.45%)
occurrences all number	4	1	0	9
Neutrophil count decreased
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	6 / 84 (7.14%)	3 / 71 (4.23%)
occurrences all number	0	0	7	4
Aspartate aminotransferase increased
subjects affected / exposed	15 / 88 (17.05%)	7 / 49 (14.29%)	4 / 84 (4.76%)	21 / 71 (29.58%)
occurrences all number	22	8	6	36
Blood alkaline phosphatase increased
subjects affected / exposed	8 / 88 (9.09%)	5 / 49 (10.20%)	4 / 84 (4.76%)	9 / 71 (12.68%)
occurrences all number	9	6	4	10
Blood creatinine increased
subjects affected / exposed	8 / 88 (9.09%)	2 / 49 (4.08%)	5 / 84 (5.95%)	20 / 71 (28.17%)
occurrences all number	10	4	5	24
Alanine aminotransferase increased
subjects affected / exposed	16 / 88 (18.18%)	4 / 49 (8.16%)	5 / 84 (5.95%)	21 / 71 (29.58%)
occurrences all number	22	5	6	35
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 88 (2.27%)	2 / 49 (4.08%)	6 / 84 (7.14%)	5 / 71 (7.04%)
occurrences all number	2	2	10	6
Nervous system disorders
Dizziness
subjects affected / exposed	7 / 88 (7.95%)	6 / 49 (12.24%)	17 / 84 (20.24%)	6 / 71 (8.45%)
occurrences all number	7	7	19	9
Dysgeusia
subjects affected / exposed	11 / 88 (12.50%)	6 / 49 (12.24%)	12 / 84 (14.29%)	9 / 71 (12.68%)
occurrences all number	12	6	14	9
Peripheral sensory neuropathy
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	5 / 84 (5.95%)	0 / 71 (0.00%)
occurrences all number	1	0	5	0
Paraesthesia
subjects affected / exposed	2 / 88 (2.27%)	3 / 49 (6.12%)	3 / 84 (3.57%)	3 / 71 (4.23%)
occurrences all number	2	3	3	3
Neuropathy peripheral
subjects affected / exposed	2 / 88 (2.27%)	2 / 49 (4.08%)	23 / 84 (27.38%)	0 / 71 (0.00%)
occurrences all number	2	2	24	0
Headache
subjects affected / exposed	8 / 88 (9.09%)	6 / 49 (12.24%)	10 / 84 (11.90%)	6 / 71 (8.45%)
occurrences all number	9	6	13	7
Syncope
subjects affected / exposed	0 / 88 (0.00%)	3 / 49 (6.12%)	3 / 84 (3.57%)	1 / 71 (1.41%)
occurrences all number	0	3	3	1
Blood and lymphatic system disorders
Leukopenia
subjects affected / exposed	5 / 88 (5.68%)	1 / 49 (2.04%)	2 / 84 (2.38%)	1 / 71 (1.41%)
occurrences all number	12	1	3	2
Anaemia
subjects affected / exposed	32 / 88 (36.36%)	15 / 49 (30.61%)	25 / 84 (29.76%)	30 / 71 (42.25%)
occurrences all number	57	22	32	39
Thrombocytopenia
subjects affected / exposed	11 / 88 (12.50%)	3 / 49 (6.12%)	2 / 84 (2.38%)	8 / 71 (11.27%)
occurrences all number	18	3	2	9
Neutropenia
subjects affected / exposed	14 / 88 (15.91%)	0 / 49 (0.00%)	14 / 84 (16.67%)	4 / 71 (5.63%)
occurrences all number	28	0	14	7
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	29 / 88 (32.95%)	9 / 49 (18.37%)	42 / 84 (50.00%)	21 / 71 (29.58%)
occurrences all number	43	11	65	42
Dyspepsia
subjects affected / exposed	3 / 88 (3.41%)	3 / 49 (6.12%)	4 / 84 (4.76%)	4 / 71 (5.63%)
occurrences all number	3	3	5	4
Nausea
subjects affected / exposed	46 / 88 (52.27%)	17 / 49 (34.69%)	36 / 84 (42.86%)	35 / 71 (49.30%)
occurrences all number	65	18	51	45
Vomiting
subjects affected / exposed	30 / 88 (34.09%)	5 / 49 (10.20%)	14 / 84 (16.67%)	18 / 71 (25.35%)
occurrences all number	45	5	20	30
Abdominal pain upper
subjects affected / exposed	4 / 88 (4.55%)	1 / 49 (2.04%)	4 / 84 (4.76%)	5 / 71 (7.04%)
occurrences all number	4	1	4	7
Abdominal pain
subjects affected / exposed	9 / 88 (10.23%)	3 / 49 (6.12%)	11 / 84 (13.10%)	5 / 71 (7.04%)
occurrences all number	9	3	12	5
Constipation
subjects affected / exposed	26 / 88 (29.55%)	10 / 49 (20.41%)	21 / 84 (25.00%)	18 / 71 (25.35%)
occurrences all number	34	12	25	19
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	10 / 88 (11.36%)	6 / 49 (12.24%)	16 / 84 (19.05%)	9 / 71 (12.68%)
occurrences all number	11	10	19	11
Rash maculo-papular
subjects affected / exposed	1 / 88 (1.14%)	4 / 49 (8.16%)	4 / 84 (4.76%)	2 / 71 (2.82%)
occurrences all number	1	6	4	4
Skin lesion
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	1 / 84 (1.19%)	4 / 71 (5.63%)
occurrences all number	2	0	1	4
Nail discolouration
subjects affected / exposed	0 / 88 (0.00%)	0 / 49 (0.00%)	7 / 84 (8.33%)	0 / 71 (0.00%)
occurrences all number	0	0	7	0
Erythema
subjects affected / exposed	4 / 88 (4.55%)	1 / 49 (2.04%)	1 / 84 (1.19%)	4 / 71 (5.63%)
occurrences all number	4	1	1	4
Dry skin
subjects affected / exposed	5 / 88 (5.68%)	4 / 49 (8.16%)	3 / 84 (3.57%)	5 / 71 (7.04%)
occurrences all number	6	4	3	5
Alopecia
subjects affected / exposed	0 / 88 (0.00%)	1 / 49 (2.04%)	28 / 84 (33.33%)	2 / 71 (2.82%)
occurrences all number	0	1	28	4
Pruritus
subjects affected / exposed	10 / 88 (11.36%)	9 / 49 (18.37%)	6 / 84 (7.14%)	11 / 71 (15.49%)
occurrences all number	11	9	6	14
Renal and urinary disorders
Urinary retention
subjects affected / exposed	3 / 88 (3.41%)	1 / 49 (2.04%)	5 / 84 (5.95%)	3 / 71 (4.23%)
occurrences all number	3	1	5	4
Haematuria
subjects affected / exposed	7 / 88 (7.95%)	1 / 49 (2.04%)	5 / 84 (5.95%)	3 / 71 (4.23%)
occurrences all number	7	1	6	4
Acute kidney injury
subjects affected / exposed	5 / 88 (5.68%)	1 / 49 (2.04%)	0 / 84 (0.00%)	0 / 71 (0.00%)
occurrences all number	5	1	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	7 / 88 (7.95%)	5 / 49 (10.20%)	4 / 84 (4.76%)	5 / 71 (7.04%)
occurrences all number	8	5	4	5
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	4 / 88 (4.55%)	0 / 49 (0.00%)	5 / 84 (5.95%)	0 / 71 (0.00%)
occurrences all number	4	0	5	0
Bone pain
subjects affected / exposed	12 / 88 (13.64%)	11 / 49 (22.45%)	8 / 84 (9.52%)	7 / 71 (9.86%)
occurrences all number	13	13	8	7
Back pain
subjects affected / exposed	20 / 88 (22.73%)	12 / 49 (24.49%)	25 / 84 (29.76%)	11 / 71 (15.49%)
occurrences all number	20	12	27	13
Arthralgia
subjects affected / exposed	17 / 88 (19.32%)	16 / 49 (32.65%)	20 / 84 (23.81%)	11 / 71 (15.49%)
occurrences all number	18	19	25	13
Muscular weakness
subjects affected / exposed	1 / 88 (1.14%)	2 / 49 (4.08%)	4 / 84 (4.76%)	6 / 71 (8.45%)
occurrences all number	1	2	4	6
Spinal pain
subjects affected / exposed	0 / 88 (0.00%)	4 / 49 (8.16%)	2 / 84 (2.38%)	0 / 71 (0.00%)
occurrences all number	0	4	2	0
Pain in extremity
subjects affected / exposed	7 / 88 (7.95%)	11 / 49 (22.45%)	10 / 84 (11.90%)	7 / 71 (9.86%)
occurrences all number	7	11	10	8
Myalgia
subjects affected / exposed	4 / 88 (4.55%)	5 / 49 (10.20%)	4 / 84 (4.76%)	5 / 71 (7.04%)
occurrences all number	5	5	6	5
Musculoskeletal pain
subjects affected / exposed	6 / 88 (6.82%)	1 / 49 (2.04%)	1 / 84 (1.19%)	3 / 71 (4.23%)
occurrences all number	6	1	1	3
Infections and infestations
Bronchitis
subjects affected / exposed	5 / 88 (5.68%)	0 / 49 (0.00%)	5 / 84 (5.95%)	1 / 71 (1.41%)
occurrences all number	5	0	5	1
Pneumonia
subjects affected / exposed	6 / 88 (6.82%)	1 / 49 (2.04%)	2 / 84 (2.38%)	6 / 71 (8.45%)
occurrences all number	7	1	2	7
Upper respiratory tract infection
subjects affected / exposed	1 / 88 (1.14%)	0 / 49 (0.00%)	5 / 84 (5.95%)	4 / 71 (5.63%)
occurrences all number	1	0	7	4
Urinary tract infection
subjects affected / exposed	5 / 88 (5.68%)	3 / 49 (6.12%)	6 / 84 (7.14%)	3 / 71 (4.23%)
occurrences all number	5	3	8	4
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	29 / 88 (32.95%)	14 / 49 (28.57%)	25 / 84 (29.76%)	21 / 71 (29.58%)
occurrences all number	34	18	29	25
Hypophosphataemia
subjects affected / exposed	3 / 88 (3.41%)	3 / 49 (6.12%)	1 / 84 (1.19%)	5 / 71 (7.04%)
occurrences all number	3	3	1	7
Hypomagnesaemia
subjects affected / exposed	3 / 88 (3.41%)	3 / 49 (6.12%)	2 / 84 (2.38%)	1 / 71 (1.41%)
occurrences all number	3	4	2	1
Hypokalaemia
subjects affected / exposed	4 / 88 (4.55%)	1 / 49 (2.04%)	4 / 84 (4.76%)	4 / 71 (5.63%)
occurrences all number	8	1	7	5
Hyperglycaemia
subjects affected / exposed	2 / 88 (2.27%)	6 / 49 (12.24%)	6 / 84 (7.14%)	2 / 71 (2.82%)
occurrences all number	5	14	11	2
Dehydration
subjects affected / exposed	2 / 88 (2.27%)	0 / 49 (0.00%)	4 / 84 (4.76%)	4 / 71 (5.63%)
occurrences all number	2	0	4	5

More information

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Were there any global substantial amendments to the protocol? Yes

22 Mar 2018

Clarification to the inclusion and exclusion criteria

10 Sep 2018

Study design update

31 Jan 2019

Timing of final analysis clarification

08 Aug 2019

Interim Analysis clarification

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.

None reported

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Clinical trials

Clinical Trial Results: A Phase 2 Study of Nivolumab in Combination with Either Rucaparib, Docetaxel, or Enzalutamide in Men with Castration-resistant Metastatic Prostate Cancer (CheckMate 9KD: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 9KD)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3)

Primary: Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3)

Primary: Prostate-Specific Antigen Response Rate (RR-PSA)

Primary: Prostate-Specific Antigen Response Rate (RR-PSA)

Secondary: Radiographic Progression-Free Survival (rPFS)

Secondary: Radiographic Progression-Free Survival (rPFS)

Secondary: Time to Response per Prostate Cancer Clinical Trials Working Group 3 (TTR-PCWG3)

Secondary: Time to Response per Prostate Cancer Clinical Trials Working Group 3 (TTR-PCWG3)

Secondary: Duration of Response per Prostate Cancer Clinical Trials Working Group 3 (DOR-PCWG3)

Secondary: Duration of Response per Prostate Cancer Clinical Trials Working Group 3 (DOR-PCWG3)

Secondary: Prostate-Specific Antigen Time to Progression (TTP-PSA)

Secondary: Prostate-Specific Antigen Time to Progression (TTP-PSA)

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Number of Participants with Adverse Events (AEs)

Secondary: Number of Participants with Adverse Events (AEs)

Secondary: Number of Participants who Died

Secondary: Number of Participants who Died

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Liver Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Secondary: Number of Participants with Laboratory Abnormalities in Specific Thyroid Tests

Secondary: Number of Participants with Laboratory Values Change from Baseline

Secondary: Number of Participants with Laboratory Values Change from Baseline

Post-hoc: Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) - Extended Collection

Post-hoc: Objective Response Rate per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) - Extended Collection

Post-hoc: Prostate-Specific Antigen Response Rate (RR-PSA) - Extended Collection

Post-hoc: Prostate-Specific Antigen Response Rate (RR-PSA) - Extended Collection

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2 Study of Nivolumab in Combination with Either Rucaparib, Docetaxel, or Enzalutamide in Men with Castration-resistant Metastatic Prostate Cancer (CheckMate 9KD: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 9KD)