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Clinical Trial Results:
TRITON3: A Multicenter, Randomized, Open-label Phase 3 Study of Rucaparib Versus Physician’s Choice of Therapy for Patients with Metastatic Castration-resistant Prostate Cancer Associated with Homologous Recombination Deficiency

Summary
EudraCT number	2016-003163-20
Trial protocol	GB IE BE ES DK DE IT
Global end of trial date	08 Aug 2024

Results information
Results version number	v1(current)
This version publication date	23 Aug 2025
First version publication date	23 Aug 2025
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

CO-338-063

ISRCTN number

US NCT number

NCT02975934

WHO universal trial number (UTN)

Sponsor organisation name

pharmaand GmbH

Sponsor organisation address

Taborstraße 1, Wien, Austria, 1020

Public contact

Medical Information Department, pharmaand GmbH, +43 13560006, medinfo@pharmaand.com

Scientific contact

Medical Information Department, pharmaand GmbH, +43 13560006, medinfo@pharmaand.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

08 Aug 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

08 Aug 2024

Was the trial ended prematurely?

Main objective of the trial

To assess the efficacy of rucaparib versus physician’s choice of treatment based on independent radiology review (IRR) of radiographic progression free survival (rPFS) in metastatic castration-resistant prostate cancer (mCRPC) participants with homologous recombination deficiency (HRD) who progressed on prior androgen receptor (AR)-directed therapy and had not yet received chemotherapy in the castration-resistant setting.

Protection of trial subjects

The study was conducted in accordance with the protocol and applicable standard operating procedures (SOPs); and in compliance with the Declaration of Helsinki, the International Council on Harmonisation Guidelines for Good Clinical Practice, and regulatory requirements as applicable.

Background therapy

Evidence for comparator

Actual start date of recruitment

13 Jun 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 13

Country: Number of subjects enrolled

Belgium: 5

Country: Number of subjects enrolled

Canada: 60

Country: Number of subjects enrolled

Denmark: 11

Country: Number of subjects enrolled

France: 36

Country: Number of subjects enrolled

Germany: 12

Country: Number of subjects enrolled

Ireland: 27

Country: Number of subjects enrolled

Israel: 11

Country: Number of subjects enrolled

Italy: 15

Country: Number of subjects enrolled

Spain: 52

Country: Number of subjects enrolled

United Kingdom: 56

Country: Number of subjects enrolled

United States: 107

Worldwide total number of subjects

405

EEA total number of subjects

158

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)

116

From 65 to 84 years

273

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants were randomized to receive rucaparib or physician’s choice of docetaxel or AR-directed therapy (abiraterone acetate or enzalutamide, whichever the participant had not yet received).

Period 1 title

Treatment Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Rucaparib

Arm description

Oral rucaparib (monotherapy).

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

CO-338

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Rucaparib was administered daily.

Abiraterone Acetate or Enzalutamide or Docetaxel

Arm description

Oral abiraterone acetate (monotherapy, given in combination with prednisone). Oral enzalutamide (monotherapy). Intravenous docetaxel (monotherapy, given in combination with prednisone or prednisolone).

Arm type

Active comparator

Investigational medicinal product name

Abiraterone acetate

Investigational medicinal product code

Other name

Zytiga

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Abiraterone acetate was administered daily.

Investigational medicinal product name

Enzalutamide

Investigational medicinal product code

Other name

Xtandi

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Enzalutamide was administered daily.

Investigational medicinal product name

Docetaxel

Investigational medicinal product code

Other name

Taxotere

Pharmaceutical forms

Solution for injection

Routes of administration

Intravenous use

Dosage and administration details

Docetaxel was administered daily.

Number of subjects in period 1	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Started	270	135
Received at least 1 dose of study drug	270	130
Safety Population	270	130
Completed	270	130
Not completed	0	5
Never initiated study drug	-	5

Period 2 title

Cross-Over Phase

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Rucaparib (Cross-Over Phase)

Arm description

Oral rucaparib (monotherapy). Rucaparib: Rucaparib was administered daily. Participants from the Abiraterone Acetate/Enzalutamide/Docetaxel arm who completed the Treatment Phase and radiographically progressed by IRR received rucaparib treatment during the Cross-Over Phase. After analysis of the primary endpoint, investigator-assessed radiographic disease progression was used for cross-over eligibility evaluation.

Arm type

Experimental

Investigational medicinal product name

Rucaparib

Investigational medicinal product code

CO-338

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Rucaparib was administered daily.

Number of subjects in period 2 ^[1]	Rucaparib (Cross-Over Phase)
Started	70
Received at least 1 dose of study drug	70
Safety Population	70
Completed	70

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Not all participants who completed Period 1 proceeded to Period 2.

Baseline characteristics

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Reporting group title

Rucaparib

Reporting group description

Oral rucaparib (monotherapy).

Reporting group title

Abiraterone Acetate or Enzalutamide or Docetaxel

Reporting group description

Reporting group values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel	Total
Number of subjects	270	135	405
Age categorical
Units: Subjects
<=18 years	0	0	0
Between 18 and 65 years	84	32	116
>=65 years	186	103	289
Age continuous
Units: years
median (full range (min-max))	70 (45 to 90)	71 (47 to 92)	-
Gender categorical
Units: Subjects
Female	0	0	0
Male	270	135	405
Ethnicity
Units: Subjects
Hispanic or Latino	3	4	7
Not Hispanic or Latino	216	103	319
Unknown or Not Reported	51	28	79
Race
Units: Subjects
American Indian or Alaska Native	1	0	1
Asian	4	1	5
Native Hawaiian or Other Pacific Islander	0	0	0
Black or African American	10	4	14
White	199	103	302
More than one race	3	0	3
Unknown or Not Reported	53	27	80
Region of Enrollment
Units: Subjects
North America	111	56	167
Europe	141	73	214
Australia	10	3	13
Israel	8	3	11
Eastern Cooperative Oncology Group (ECOG) Performance Status (at Stratification)
ECOG Performance Status Scale. ECOG 0 = Fully active, able to carry on all pre-disease performance without restriction. ECOG 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (for example, light house work or office work).
Units: Subjects
ECOG 0	132	68	200
ECOG 1	138	67	205
Gene Alteration (at stratification)
BRCA1 =  Breast Cancer 1 Gene BRCA2 =  Breast Cancer 2 Gene ATM = Ataxia Telangiectasia Mutated Serine/Threonine Kinase
Units: Subjects
BRCA1	29	15	44
BRCA2	172	86	258
ATM	69	34	103
Prior Therapies for Castration-resistant Prostate Cancer (CRPC)
Units: Subjects
0 therapy	48	26	74
≥1 therapy	222	109	331
Gleason score ≥8 at diagnosis
Units: Subjects
Gleason score ≥8	173	96	269
Gleason score <8	97	39	136
Measurable Disease per IRR
Units: Subjects
Yes	106	55	161
No	164	80	244
Baseline prostate specific antigen (PSA)
Units: nanograms (ng)/milliliter (mL)
median (full range (min-max))	26.9 (0.1 to 1247)	28.8 (0 to 1039)	-

End points

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Reporting group title

Rucaparib

Reporting group description

Oral rucaparib (monotherapy).

Reporting group title

Abiraterone Acetate or Enzalutamide or Docetaxel

Reporting group description

Reporting group title

Rucaparib (Cross-Over Phase)

Reporting group description

Primary: rPFS by IRR in Participants With a Breast Cancer Gene (BRCA) Alteration

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End point title

rPFS by IRR in Participants With a Breast Cancer Gene (BRCA) Alteration

End point description

rPFSirr was defined as time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurred first). Radiographic disease progression included confirmed soft tissue disease progression and confirmed bone disease progression per modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (≥20% increase in sum of the longest diameter [LD] of target lesions or appearance of ≥1 new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or progression by bone determined by Prostate Cancer Working Group 3 (PCWG3) criteria (≥2 new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in confirmatory scan appearing after 12-week flare window; or after the 12-week flare window, ≥2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan). Intent-to-treat (ITT) Population with BRCA mutated mCRPC.

End point type

Primary

End point timeframe

From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	201	101
Units: months
median (confidence interval 95%)	11.2 (9.2 to 13.8)	6.4 (5.4 to 8.3)

Statistical Analysis 1

Comparison groups

Rucaparib v Abiraterone Acetate or Enzalutamide or Docetaxel

Number of subjects included in analysis

302

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

0.69

Primary: rPFS by IRR in Participants With a BRCA or ATM Alteration Combined

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End point title

rPFS by IRR in Participants With a BRCA or ATM Alteration Combined

End point description

rPFSirr was defined as time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurred first). Radiographic disease progression included confirmed soft tissue disease progression and confirmed bone disease progression per modified RECIST Version 1.1 (≥20% increase in sum of the LD of target lesions or appearance of ≥1 new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or progression by bone determined by PCWG3 criteria (≥2 new lesions appearing during first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window; or after the 12-week flare window, ≥2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan). ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC).

End point type

Primary

End point timeframe

From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	270	135
Units: months
median (confidence interval 95%)	10.2 (8.3 to 11.2)	6.4 (5.6 to 8.2)

Statistical Analysis 1

Comparison groups

Rucaparib v Abiraterone Acetate or Enzalutamide or Docetaxel

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.47

upper limit

0.8

Secondary: Overall Survival (OS) in Participants With a BRCA Alteration

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End point title

Overall Survival (OS) in Participants With a BRCA Alteration

End point description

The OS time was calculated as the time from randomization to death (by any cause) +1 day. Participants who did not die were censored on the date the participant was last known to be alive. ITT Population with BRCA mutated mCRPC.

End point type

Secondary

End point timeframe

From enrollment to completion of study (up to approximately 7 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	201	101
Units: months
median (confidence interval 95%)	23.2 (19.1 to 25.2)	21.2 (18.0 to 23.1)

Statistical Analysis 1

Comparison groups

Rucaparib v Abiraterone Acetate or Enzalutamide or Docetaxel

Number of subjects included in analysis

302

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5044

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.91

Confidence interval

level

95%

sides

2-sided

lower limit

0.68

upper limit

1.2

Secondary: OS in Participants With a BRCA or ATM Alteration Combined

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End point title

OS in Participants With a BRCA or ATM Alteration Combined

End point description

The OS time was calculated as the time from randomization to death (by any cause) +1 day. Participants who did not die were censored on the date the participants was last known to be alive. ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC).

End point type

Secondary

End point timeframe

From enrollment to completion of study (up to approximately 7 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	270	135
Units: months
median (confidence interval 95%)	22.8 (19.0 to 24.2)	21.7 (18.9 to 23.3)

Statistical Analysis 1

Comparison groups

Rucaparib v Abiraterone Acetate or Enzalutamide or Docetaxel

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9368

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.99

Confidence interval

level

95%

sides

2-sided

lower limit

0.78

upper limit

1.26

Secondary: Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration

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End point title

Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration

End point description

ORR was defined as the percentage of participants with a confirmed best response of Complete Response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria was used to determine ORR (that is, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment). CR was disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). PR was at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. ITT Population with BRCA mutated mCRPC and measurable disease at baseline.

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	82	41
Units: participants	37	7

No statistical analyses for this end point

Secondary: ORR by IRR in Participants With a BRCA or ATM Alteration Combined

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End point title

ORR by IRR in Participants With a BRCA or ATM Alteration Combined

End point description

ORR was defined as the percentage of participants with a confirmed best response of CR or PR in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria was used to determine ORR (that is, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment). CR was disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm. PR was at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC) with measurable disease at baseline.

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	106	55
Units: participants	37	9

No statistical analyses for this end point

Secondary: Duration of Response (DOR) by IRR in Participants With a BRCA Alteration

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End point title

Duration of Response (DOR) by IRR in Participants With a BRCA Alteration

End point description

DOR was defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) was documented. ITT Population with BRCA mutated mCRPC and measurable disease at baseline. ‘Overall number of participants analyzed’ = participants with objective response. '9999' signifies 'the upper limit of the confidence interval (CI) is inestimable likely due to the small number of participants in this treatment group'.

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	37	7
Units: months
median (confidence interval 95%)	7.4 (6.4 to 12.7)	7.4 (3.5 to 9999)

No statistical analyses for this end point

Secondary: DOR by IRR in Participants With a BRCA or ATM Alteration Combined

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End point title

DOR by IRR in Participants With a BRCA or ATM Alteration Combined

End point description

DOR was defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that PD (using the same criteria) was documented. ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC) with measurable disease at baseline. ‘Overall number of participants analyzed’ = participants with objective response.

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	37	9
Units: months
median (confidence interval 95%)	7.4 (6.4 to 12.7)	7.4 (3.5 to 14.5)

No statistical analyses for this end point

Secondary: PSA Response in Participants With a BRCA Alteration

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End point title

PSA Response in Participants With a BRCA Alteration

End point description

Confirmed PSA response was defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response was calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA was assessed by a local laboratory. ITT Population with BRCA mutated mCRPC.

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (up to approximately 5 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	201	101
Units: percentage of participants
number (not applicable)	54.7	26.7

No statistical analyses for this end point

Secondary: PSA Response in Participants With a BRCA or ATM Alteration Combined

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End point title

PSA Response in Participants With a BRCA or ATM Alteration Combined

End point description

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (up to approximately 5 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	270	135
Units: percentage of participants
number (not applicable)	41.9	26.7

No statistical analyses for this end point

Secondary: Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration

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End point title

Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration

End point description

Defined as the percentage of participants with a CR, PR, and stable disease (SD) according to modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria. The Safety Population included all participants with BRCA mutated mCRPC who received at least one dose of protocol-specified treatment and had 6 months of follow-up prior to the data cutoff.

End point type

Secondary

End point timeframe

From enrollment to 6 months

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	200	97
Units: percentage of participants
number (not applicable)	63.0	22.7

No statistical analyses for this end point

Secondary: CBR by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined

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End point title

CBR by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined

End point description

Defined as the percentage of participants with a CR, PR, and SD, according to Modified RECIST Version 1.1 with no progression in bone per PCWG3 Criteria. The Safety Population included all participants who received at least one dose of protocol-specified treatment and had 6 months of follow-up prior to the data cutoff.

End point type

Secondary

End point timeframe

From enrollment to 6 months

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	269	130
Units: percentage of participants
number (not applicable)	57.6	25.4

No statistical analyses for this end point

Secondary: Time to PSA Progression in Participants With a BRCA Alteration

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End point title

Time to PSA Progression in Participants With a BRCA Alteration

End point description

Time to PSA progression was defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA). The increase was confirmed by a second consecutive assessment conducted at least 3 weeks later. ITT Population with BRCA mutated mCRPC.

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (up to approximately 5 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	201	101
Units: months
median (confidence interval 95%)	6.6 (5.9 to 7.7)	3.8 (3.1 to 4.5)

No statistical analyses for this end point

Secondary: Time to PSA Progression in Participants With a BRCA or ATM Alteration Combined

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End point title

Time to PSA Progression in Participants With a BRCA or ATM Alteration Combined

End point description

End point type

Secondary

End point timeframe

From enrollment to primary completion of study (up to approximately 5 years)

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	270	135
Units: months
median (confidence interval 95%)	5.7 (4.6 to 6.5)	3.6 (3.5 to 4.5)

No statistical analyses for this end point

Secondary: Change From Baseline in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: Functional Assessment of Cancer Therapy–Prostate (FACT-P)

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End point title

Change From Baseline in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: Functional Assessment of Cancer Therapy–Prostate (FACT-P)

End point description

Changes in health and pain status from baseline to Week 25 using: FACT-P total score (on a scale of 0 to 156 where a higher score is better quality of life). The greater the decrease in score (that is, more negative) from baseline to Week 25 the greater the decrease in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter), during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase. ITT Population with BRCA mutated mCRPC. Here, ‘Overall number of participants analyzed’ = participants evaluable for this outcome measure.

End point type

Secondary

End point timeframe

From enrollment to up to approximately 25 weeks

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	136	35
Units: units on a scale
least squares mean (standard error)	-0.8 ( 1.13 )	-3.9 ( 2.23 )

No statistical analyses for this end point

Secondary: Change from Baseline in PRO in Participants With a BRCA Alteration: Brief Pain Inventory–Short Form (BPI-SF)

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End point title

Change from Baseline in PRO in Participants With a BRCA Alteration: Brief Pain Inventory–Short Form (BPI-SF)

End point description

Changes in health and pain status from baseline to week 25 using BPI-SF questionnaire (on a scale of 1 to 10, from mild to severe, for pain and pain-interference scores). A decrease indicates less severe pain/interference. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter), during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase. ITT Population with BRCA mutated mCRPC. Here, ‘Overall number of participants analyzed’ = participants evaluable for this outcome measure. ‘n’ = participants evaluable for specified category.

End point type

Secondary

End point timeframe

From enrollment to up to approximately 25 weeks

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	133	32
Units: units on a scale
arithmetic mean (standard error)
BPI-SF Pain Score (n=133,32)	-0.32 ( 0.139 )	0.14 ( 0.285 )
BPI-SF Interference Score (n=130,31)	-0.28 ( 0.147 )	0.65 ( 0.302 )

No statistical analyses for this end point

Secondary: Change From Baseline in PRO in Participants With a BRCA Alteration: EuroQol 5 Dimensions 5 Level Questionnaire (EQ-5D-5L)

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End point title

Change From Baseline in PRO in Participants With a BRCA Alteration: EuroQol 5 Dimensions 5 Level Questionnaire (EQ-5D-5L)

End point description

Changes in health and pain status from baseline to Week 25 using EuroQol-5D-5L Visual Analogue Scale (VAS); on a scale from 100 to 0, from best to worst health status). The greater the increase in score (including more negative) from baseline to Week 25 the greater the increase in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter), during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase. ITT Population with BRCA mutated mCRPC. Here, ‘Overall number of participants analyzed’ = participants evaluable for this outcome measure.

End point type

Secondary

End point timeframe

From enrollment to up to approximately 25 weeks

End point values	Rucaparib	Abiraterone Acetate or Enzalutamide or Docetaxel
Number of subjects analysed	136	36
Units: units on a scale
least squares mean (standard error)	2.4 ( 1.23 )	1.8 ( 2.39 )

No statistical analyses for this end point

Secondary: Trough Plasma Pharmacokinetic (PK) (Cmin) of Rucaparib Based on Sparse Sampling

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End point title

Trough Plasma Pharmacokinetic (PK) (Cmin) of Rucaparib Based on Sparse Sampling ^[1]

End point description

Mean trough PK plasma concentration over time in the safety population with at least one PK sample collected at timepoints Week 5, 9, 13 and 17; only Week 5 data presented. Safety Population with at least 1 PK sample collected.

End point type

Secondary

End point timeframe

From enrollment to Week 5 of dosing

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The endpoint is reporting statistics for the specified arm only.

End point values	Rucaparib
Number of subjects analysed	228
Units: ng/mL
median (full range (min-max))	1310 (5.5 to 4180)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose of study drug through 28 days after receiving the last dose of study drug (approximately 7 years). The Safety Population included all participants who received at least 1 dose of study drug.

Adverse event reporting additional description

SAEs and AEs were assessed in the Safety Population. After 28 days following last dose of study drug, only SAEs assessed as potentially related to study drug are reported. Events of progression of the participant's underlying cancer, and progression of disease leading to death are not reported as an AE or SAE.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Rucaparib (Treatment Phase)

Reporting group description

Oral rucaparib (monotherapy).

Reporting group title

Abiraterone Acetate/Enzalutamide/Docetaxel (Treatment Phase)

Reporting group description

Reporting group title

Rucaparib (Cross-over Phase)

Reporting group description

Serious adverse events	Rucaparib (Treatment Phase)	Abiraterone Acetate/Enzalutamide/Docetaxel (Treatment Phase)	Rucaparib (Cross-over Phase)
Total subjects affected by serious adverse events
subjects affected / exposed	81 / 270 (30.00%)	36 / 130 (27.69%)	18 / 70 (25.71%)
number of deaths (all causes)	6	3	1
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malignant melanoma
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malignant neoplasm of eyelid
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metastatic malignant melanoma
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophageal squamous cell carcinoma
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombophlebitis superficial
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0
Fatigue
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Systemic inflammatory response syndrome
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Bronchopneumopathy
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 270 (0.00%)	2 / 130 (1.54%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	5 / 270 (1.85%)	4 / 130 (3.08%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 5	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Investigations
Blood bilirubin increased
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutrophil count decreased
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Subdural haemorrhage
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	3 / 270 (1.11%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic cardiomyopathy
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	2 / 70 (2.86%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neuralgia
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sacral radiculopathy
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal cord compression
subjects affected / exposed	0 / 270 (0.00%)	2 / 130 (1.54%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	2 / 70 (2.86%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	2 / 270 (0.74%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	9 / 270 (3.33%)	0 / 130 (0.00%)	2 / 70 (2.86%)
occurrences causally related to treatment / all	8 / 9	0 / 0	3 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	1 / 270 (0.37%)	8 / 130 (6.15%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 1	11 / 11	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Splenic haematoma
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal detachment
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	3 / 270 (1.11%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophageal fistula
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophageal perforation
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	2 / 2	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholangitis
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatic cirrhosis
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatotoxicity
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	8 / 270 (2.96%)	0 / 130 (0.00%)	2 / 70 (2.86%)
occurrences causally related to treatment / all	4 / 9	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 270 (0.37%)	2 / 130 (1.54%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bone pain
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Compartment syndrome
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	2 / 270 (0.74%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Spinal stenosis
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 270 (0.00%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Blastocystis infection
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	3 / 270 (1.11%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 270 (0.00%)	2 / 130 (1.54%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Campylobacter infection
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dermo-hypodermitis
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	8 / 270 (2.96%)	1 / 130 (0.77%)	3 / 70 (4.29%)
occurrences causally related to treatment / all	0 / 8	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	2 / 270 (0.74%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Salmonella bacteraemia
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 270 (0.74%)	2 / 130 (1.54%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 2	1 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	7 / 270 (2.59%)	1 / 130 (0.77%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	2 / 10	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	0 / 270 (0.00%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	3 / 270 (1.11%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 270 (0.37%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	5 / 270 (1.85%)	0 / 130 (0.00%)	1 / 70 (1.43%)
occurrences causally related to treatment / all	0 / 5	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 270 (0.37%)	1 / 130 (0.77%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Malnutrition
subjects affected / exposed	2 / 270 (0.74%)	0 / 130 (0.00%)	0 / 70 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Rucaparib (Treatment Phase)	Abiraterone Acetate/Enzalutamide/Docetaxel (Treatment Phase)	Rucaparib (Cross-over Phase)
Total subjects affected by non serious adverse events
subjects affected / exposed	270 / 270 (100.00%)	127 / 130 (97.69%)	67 / 70 (95.71%)
Vascular disorders
Hot flush
subjects affected / exposed	17 / 270 (6.30%)	3 / 130 (2.31%)	3 / 70 (4.29%)
occurrences all number	18	5	3
Hypertension
subjects affected / exposed	18 / 270 (6.67%)	11 / 130 (8.46%)	5 / 70 (7.14%)
occurrences all number	36	16	15
General disorders and administration site conditions
Asthenia
subjects affected / exposed	58 / 270 (21.48%)	20 / 130 (15.38%)	9 / 70 (12.86%)
occurrences all number	136	36	12
Fatigue
subjects affected / exposed	117 / 270 (43.33%)	63 / 130 (48.46%)	23 / 70 (32.86%)
occurrences all number	203	123	41
Oedema peripheral
subjects affected / exposed	55 / 270 (20.37%)	21 / 130 (16.15%)	14 / 70 (20.00%)
occurrences all number	70	29	15
Pyrexia
subjects affected / exposed	15 / 270 (5.56%)	7 / 130 (5.38%)	6 / 70 (8.57%)
occurrences all number	17	11	6
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	27 / 270 (10.00%)	17 / 130 (13.08%)	8 / 70 (11.43%)
occurrences all number	28	17	10
Dyspnoea
subjects affected / exposed	45 / 270 (16.67%)	15 / 130 (11.54%)	6 / 70 (8.57%)
occurrences all number	66	21	6
Pulmonary embolism
subjects affected / exposed	6 / 270 (2.22%)	7 / 130 (5.38%)	1 / 70 (1.43%)
occurrences all number	6	7	1
Psychiatric disorders
Insomnia
subjects affected / exposed	22 / 270 (8.15%)	14 / 130 (10.77%)	2 / 70 (2.86%)
occurrences all number	23	16	2
Investigations
Alanine aminotransferase increased
subjects affected / exposed	67 / 270 (24.81%)	3 / 130 (2.31%)	19 / 70 (27.14%)
occurrences all number	146	3	44
Aspartate aminotransferase increased
subjects affected / exposed	65 / 270 (24.07%)	4 / 130 (3.08%)	20 / 70 (28.57%)
occurrences all number	120	5	46
Blood alkaline phosphatase increased
subjects affected / exposed	17 / 270 (6.30%)	2 / 130 (1.54%)	2 / 70 (2.86%)
occurrences all number	19	2	3
Blood bilirubin increased
subjects affected / exposed	13 / 270 (4.81%)	1 / 130 (0.77%)	7 / 70 (10.00%)
occurrences all number	43	1	17
Blood creatinine increased
subjects affected / exposed	55 / 270 (20.37%)	6 / 130 (4.62%)	8 / 70 (11.43%)
occurrences all number	97	8	10
Lymphocyte count decreased
subjects affected / exposed	11 / 270 (4.07%)	7 / 130 (5.38%)	4 / 70 (5.71%)
occurrences all number	27	10	9
Neutrophil count decreased
subjects affected / exposed	17 / 270 (6.30%)	5 / 130 (3.85%)	4 / 70 (5.71%)
occurrences all number	64	5	11
Platelet count decreased
subjects affected / exposed	29 / 270 (10.74%)	0 / 130 (0.00%)	4 / 70 (5.71%)
occurrences all number	103	0	20
Weight decreased
subjects affected / exposed	40 / 270 (14.81%)	15 / 130 (11.54%)	10 / 70 (14.29%)
occurrences all number	65	21	18
White blood cell count decreased
subjects affected / exposed	18 / 270 (6.67%)	3 / 130 (2.31%)	7 / 70 (10.00%)
occurrences all number	52	7	27
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	11 / 270 (4.07%)	7 / 130 (5.38%)	1 / 70 (1.43%)
occurrences all number	11	7	1
Fall
subjects affected / exposed	15 / 270 (5.56%)	6 / 130 (4.62%)	3 / 70 (4.29%)
occurrences all number	22	7	3
Nervous system disorders
Dizziness
subjects affected / exposed	37 / 270 (13.70%)	11 / 130 (8.46%)	6 / 70 (8.57%)
occurrences all number	44	12	6
Dysgeusia
subjects affected / exposed	45 / 270 (16.67%)	18 / 130 (13.85%)	7 / 70 (10.00%)
occurrences all number	48	22	8
Headache
subjects affected / exposed	31 / 270 (11.48%)	9 / 130 (6.92%)	5 / 70 (7.14%)
occurrences all number	42	10	6
Neuropathy peripheral
subjects affected / exposed	9 / 270 (3.33%)	18 / 130 (13.85%)	1 / 70 (1.43%)
occurrences all number	9	20	1
Peripheral sensory neuropathy
subjects affected / exposed	8 / 270 (2.96%)	11 / 130 (8.46%)	2 / 70 (2.86%)
occurrences all number	8	16	2
Taste disorder
subjects affected / exposed	7 / 270 (2.59%)	7 / 130 (5.38%)	2 / 70 (2.86%)
occurrences all number	7	8	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	121 / 270 (44.81%)	24 / 130 (18.46%)	26 / 70 (37.14%)
occurrences all number	435	30	90
Neutropenia
subjects affected / exposed	17 / 270 (6.30%)	6 / 130 (4.62%)	4 / 70 (5.71%)
occurrences all number	37	6	5
Thrombocytopenia
subjects affected / exposed	24 / 270 (8.89%)	0 / 130 (0.00%)	6 / 70 (8.57%)
occurrences all number	44	0	8
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	21 / 270 (7.78%)	10 / 130 (7.69%)	3 / 70 (4.29%)
occurrences all number	23	11	6
Abdominal pain upper
subjects affected / exposed	15 / 270 (5.56%)	3 / 130 (2.31%)	3 / 70 (4.29%)
occurrences all number	15	4	3
Constipation
subjects affected / exposed	76 / 270 (28.15%)	19 / 130 (14.62%)	12 / 70 (17.14%)
occurrences all number	101	23	16
Diarrhoea
subjects affected / exposed	85 / 270 (31.48%)	36 / 130 (27.69%)	10 / 70 (14.29%)
occurrences all number	118	49	11
Dyspepsia
subjects affected / exposed	18 / 270 (6.67%)	5 / 130 (3.85%)	0 / 70 (0.00%)
occurrences all number	25	6	0
Nausea
subjects affected / exposed	137 / 270 (50.74%)	25 / 130 (19.23%)	26 / 70 (37.14%)
occurrences all number	222	44	41
Stomatitis
subjects affected / exposed	12 / 270 (4.44%)	10 / 130 (7.69%)	0 / 70 (0.00%)
occurrences all number	20	15	0
Vomiting
subjects affected / exposed	65 / 270 (24.07%)	11 / 130 (8.46%)	12 / 70 (17.14%)
occurrences all number	98	16	25
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	5 / 270 (1.85%)	26 / 130 (20.00%)	2 / 70 (2.86%)
occurrences all number	5	28	2
Dry skin
subjects affected / exposed	23 / 270 (8.52%)	10 / 130 (7.69%)	2 / 70 (2.86%)
occurrences all number	24	12	2
Photosensitivity reaction
subjects affected / exposed	27 / 270 (10.00%)	0 / 130 (0.00%)	6 / 70 (8.57%)
occurrences all number	39	0	7
Pruritus
subjects affected / exposed	22 / 270 (8.15%)	5 / 130 (3.85%)	2 / 70 (2.86%)
occurrences all number	24	9	2
Rash
subjects affected / exposed	19 / 270 (7.04%)	4 / 130 (3.08%)	5 / 70 (7.14%)
occurrences all number	27	4	6
Renal and urinary disorders
Haematuria
subjects affected / exposed	15 / 270 (5.56%)	8 / 130 (6.15%)	4 / 70 (5.71%)
occurrences all number	17	9	4
Urinary retention
subjects affected / exposed	5 / 270 (1.85%)	1 / 130 (0.77%)	5 / 70 (7.14%)
occurrences all number	5	1	7
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	52 / 270 (19.26%)	28 / 130 (21.54%)	9 / 70 (12.86%)
occurrences all number	69	41	11
Back pain
subjects affected / exposed	65 / 270 (24.07%)	26 / 130 (20.00%)	13 / 70 (18.57%)
occurrences all number	97	31	19
Bone pain
subjects affected / exposed	15 / 270 (5.56%)	4 / 130 (3.08%)	3 / 70 (4.29%)
occurrences all number	19	4	3
Muscular weakness
subjects affected / exposed	13 / 270 (4.81%)	4 / 130 (3.08%)	4 / 70 (5.71%)
occurrences all number	15	4	6
Musculoskeletal chest pain
subjects affected / exposed	16 / 270 (5.93%)	6 / 130 (4.62%)	6 / 70 (8.57%)
occurrences all number	20	8	7
Musculoskeletal pain
subjects affected / exposed	26 / 270 (9.63%)	11 / 130 (8.46%)	5 / 70 (7.14%)
occurrences all number	29	15	5
Myalgia
subjects affected / exposed	14 / 270 (5.19%)	9 / 130 (6.92%)	1 / 70 (1.43%)
occurrences all number	15	10	1
Pain in extremity
subjects affected / exposed	34 / 270 (12.59%)	14 / 130 (10.77%)	8 / 70 (11.43%)
occurrences all number	48	18	17
Infections and infestations
COVID-19
subjects affected / exposed	16 / 270 (5.93%)	5 / 130 (3.85%)	3 / 70 (4.29%)
occurrences all number	17	5	3
Urinary tract infection
subjects affected / exposed	20 / 270 (7.41%)	3 / 130 (2.31%)	7 / 70 (10.00%)
occurrences all number	29	3	11
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	99 / 270 (36.67%)	29 / 130 (22.31%)	18 / 70 (25.71%)
occurrences all number	139	43	27
Dehydration
subjects affected / exposed	9 / 270 (3.33%)	3 / 130 (2.31%)	4 / 70 (5.71%)
occurrences all number	9	4	4
Hypertriglyceridaemia
subjects affected / exposed	17 / 270 (6.30%)	4 / 130 (3.08%)	3 / 70 (4.29%)
occurrences all number	51	5	16
Hypokalaemia
subjects affected / exposed	12 / 270 (4.44%)	10 / 130 (7.69%)	2 / 70 (2.86%)
occurrences all number	16	17	2
Hypophosphataemia
subjects affected / exposed	19 / 270 (7.04%)	7 / 130 (5.38%)	2 / 70 (2.86%)
occurrences all number	34	13	3

More information

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Were there any global substantial amendments to the protocol? Yes

07 Dec 2017

It included following changes: - Updated the inclusion criterion for renal function to remove the requirement for serum creatinine ≤1.5 * upper limit of normal (ULN), as glomerular filtration rate (calculated by Cockcroft-Gault) was considered a more appropriate measure (age corrected) for older participants. - Added details and updates to the description of modified RECIST response evaluation and to the PCWG3 criteria for confirmation of disease progression in bone. - Updated version of the EQ-5D-5L Health Questionnaire provided to clarify version to be used in this study. - Clarification that progressive disease was not an adverse event. - Provided requirements on age of archival tissue for homologous recombination repair (HRR) gene testing to improve the probability of satisfactory testing results. Additionally, reinforced that if archival tissue testing in Pre-screening failed, that participant should provide tissue during Screening.

19 Jun 2018

It included following changes: - Agents that target the AR pathway that were given for metastatic hormone-sensitive prostate cancer and for non-metastatic castrate-resistant cancer were now considered to meet prior AR-therapy requirements. - Implemented a stand-alone Pre-Screening Phase for the confirmation of deleterious BRCA1/2 and ATM gene mutation in tumor tissue. - Allowed participants to be eligible if they had received radiation therapy within 14 days prior to enrolment, since the use of palliative radiotherapy for treatment of bony metastases was allowed during the study, and since separate eligibility criteria required recovery from any toxicities related to prior treatment. - Included clarifications in dose modification that investigators might judge when participants should resume study drug cases of disease-related anemia. - Re-treatment criteria had been integrated with dose modification guidelines.

27 Aug 2020

It included following changes: - To achieve a better understanding of whether there was a relationship between pneumonitis and rucaparib treatment, Clovis was designating pneumonitis as an adverse events of special interests (AESI) to gather information on all reported cases. - Updated the interval after the last dose of study drug for which men must use contraceptive measures or abstinence or refrain from donating semen, including the specifications for female partners of the men in the study. The interval changed from 6 months to 3 months and was correspond with the latest approved Investigator’s Brochure and product information. - There was clarification throughout the protocol that participants in the Cross-over Phase will not be evaluated by IRR, just by investigator assessment of radiography, and that the interval to initiate treatment with rucaparib in the Cross-over Phase might be >28 days, with sponsor approval. - Clarified that participants might be permitted to cross over to rucaparib treatment if intervening systemic anticancer therapy was administered urgently after Treatment of Physician’s Choice. - Decreased the acceptable level of hemoglobin from ≥10 grams (g)/deciliter (dL) to ≥9 g/dL as part of a participant having adequate bone marrow function to be eligible to cross over from the comparator Treatment of Physician’s Choice to rucaparib. - Changes were made in relation to removing timepoints for collection of blood samples that were not needed for the analysis of circulating cell-free tumor deoxyribonucleic acid (ctDNA).

18 Feb 2022

Amendment 4 replaced Amendment 3 of the study CO-338-063 protocol, globally, including the Germany-specific version. Significant changes are summarized as follows: • Statistical analyses in the amendment were revised to align with the SAP and following consultation with the FDA. Changes incorporated in the amendment included: • Elevating the OS endpoint to the first secondary endpoint in the step-down analysis procedure. • Adding the Haybittle-Peto stopping rule to adjust for multiple OS analyses since OS data at the time of the primary PFS analysis are anticipated to be immature. A final OS analysis will be performed when these data are mature. • Clarifying the official statistical test used in the hierarchical testing of PFS and OS will be the log-rank test. • Removing the DOR and PSA endpoints from the step-down procedure. The revised step-down procedure will include rPFS by central IRR, OS, then ORR. • Incorporating description of adjustment to eliminate small stratification analyses (eg, < 5 patients). • Clarifying that the ORR endpoint will be analyzed using a CMH test. • Clarified that rPFS assessments specifically by IRR would be removed after patient data unblinding for the primary endpoint analysis, to facilitate subsequent analyses and long-term follow-up of patients using rPFS assessed by investigator only. Radiographic scans would no longer be necessary and did not need to be submitted for IRR after unblinding patient data. • Clarified that after the analysis of the primary endpoint was completed, for patients remaining on TPC, the eligibility for cross over (to rucaparib) would be determined by radiographic progression as assessed by the investigator and scans no longer needed to be read by IRR. • Revised the End-of-Study language. • Aligned the contraceptive measures with the current version of the rucaparib IB. • Clarified the collection of pneumonitis and similar events if they occur after the 28-day safety follow-up period.

27 Nov 2023

Amendment 5 updated the Study Responsibility and Sponsorship from Clovis Oncology to pharmaand GmbH and Removal of the requirement to collect the following research samples as the primary analysis has been conducted: Biomarker Analysis – ctDNA/genomic DNA from Blood, Pharmacokinetics Evaluation and Post-progression Tumor Biopsy (Optional).

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: TRITON3: A Multicenter, Randomized, Open-label Phase 3 Study of Rucaparib Versus Physician’s Choice of Therapy for Patients with Metastatic Castration-resistant Prostate Cancer Associated with Homologous Recombination Deficiency

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: rPFS by IRR in Participants With a Breast Cancer Gene (BRCA) Alteration

Primary: rPFS by IRR in Participants With a Breast Cancer Gene (BRCA) Alteration

Primary: rPFS by IRR in Participants With a BRCA or ATM Alteration Combined

Primary: rPFS by IRR in Participants With a BRCA or ATM Alteration Combined

Secondary: Overall Survival (OS) in Participants With a BRCA Alteration

Secondary: Overall Survival (OS) in Participants With a BRCA Alteration

Secondary: OS in Participants With a BRCA or ATM Alteration Combined

Secondary: OS in Participants With a BRCA or ATM Alteration Combined

Secondary: Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration

Secondary: Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration

Secondary: ORR by IRR in Participants With a BRCA or ATM Alteration Combined

Secondary: ORR by IRR in Participants With a BRCA or ATM Alteration Combined

Secondary: Duration of Response (DOR) by IRR in Participants With a BRCA Alteration

Secondary: Duration of Response (DOR) by IRR in Participants With a BRCA Alteration

Secondary: DOR by IRR in Participants With a BRCA or ATM Alteration Combined

Secondary: DOR by IRR in Participants With a BRCA or ATM Alteration Combined

Secondary: PSA Response in Participants With a BRCA Alteration

Secondary: PSA Response in Participants With a BRCA Alteration

Secondary: PSA Response in Participants With a BRCA or ATM Alteration Combined

Secondary: PSA Response in Participants With a BRCA or ATM Alteration Combined

Secondary: Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration

Secondary: Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration

Secondary: CBR by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined

Secondary: CBR by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined

Secondary: Time to PSA Progression in Participants With a BRCA Alteration

Secondary: Time to PSA Progression in Participants With a BRCA Alteration

Secondary: Time to PSA Progression in Participants With a BRCA or ATM Alteration Combined

Secondary: Time to PSA Progression in Participants With a BRCA or ATM Alteration Combined

Secondary: Change From Baseline in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: Functional Assessment of Cancer Therapy–Prostate (FACT-P)

Secondary: Change From Baseline in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: Functional Assessment of Cancer Therapy–Prostate (FACT-P)

Secondary: Change from Baseline in PRO in Participants With a BRCA Alteration: Brief Pain Inventory–Short Form (BPI-SF)

Secondary: Change from Baseline in PRO in Participants With a BRCA Alteration: Brief Pain Inventory–Short Form (BPI-SF)

Secondary: Change From Baseline in PRO in Participants With a BRCA Alteration: EuroQol 5 Dimensions 5 Level Questionnaire (EQ-5D-5L)

Secondary: Change From Baseline in PRO in Participants With a BRCA Alteration: EuroQol 5 Dimensions 5 Level Questionnaire (EQ-5D-5L)

Secondary: Trough Plasma Pharmacokinetic (PK) (Cmin) of Rucaparib Based on Sparse Sampling

Secondary: Trough Plasma Pharmacokinetic (PK) (Cmin) of Rucaparib Based on Sparse Sampling

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
TRITON3: A Multicenter, Randomized, Open-label Phase 3 Study of Rucaparib Versus Physician’s Choice of Therapy for Patients with Metastatic Castration-resistant Prostate Cancer Associated with Homologous Recombination Deficiency