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Genital Diseases, Male

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

Abiraterone acetate and enzalutamide will be administered daily. Docetaxel will be administered every 3 weeks.

Abiraterone acetate or Enzalutamide or Docetaxel

The purpose of this study is to determine how participants with metastatic castration-resistant prostate cancer, and evidence of a homologous recombination gene deficiency, respond to treatment with rucaparib versus treatment with physician's choice of abiraterone acetate, enzalutamide, or docetaxel.

A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency

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

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by zr pharma\& Austria GmbH

The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).

Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the 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, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).

The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).

Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria (Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the 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, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan).

Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participant was last known to be alive.

Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participants was last known to be alive.

ORR is 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 is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).

CR is 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 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

DOR is 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) is documented.

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

Defined as the percentage of participants with a complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria.

Defined as the percentage of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD), according to Modified RECIST Version 1.1 with no progression in bone per PCWG3 Criteria.

Time to PSA progression is 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) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later.

Changes in health and pain status from baseline to week 25 using: Functional Assessment of Cancer Therapy-Prostate questionnaire (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 (ie 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.

Changes in health and pain status from baseline to week 25 using: Brief Pain Inventory-Short Form (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.

Changes in health and pain status from baseline to week 25 using: EuroQol-5D-5L Visual Analogue Scale (EQ-5D-5L 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.

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.

Foundation Medicine

pharmaand GmbH

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 as well as events clearly related to progression of the participant's cancer (signs and symptoms of progression) and progression of disease leading to death are not reported as an AE or SAE.

Oral rucaparib (monotherapy).

Rucaparib: Rucaparib will be administered daily.

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

Abiraterone acetate or Enzalutamide or Docetaxel: Abiraterone acetate and enzalutamide will be administered daily.

Docetaxel will be administered every 3 weeks.

Abiraterone Acetate or Enzalutamide or Docetaxel

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

North America

Europe

Australia

Israel

Region of Enrollment

Measure Description: Eastern Cooperative Oncology Group (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 (eg, light house work or office work)

ECOG Performance Status (at stratification)

Gene Alteration (at stratification)

Baseline prostate specific antigen (PSA)

The scale for the Gleason score ranges from 2 to 10, with higher scores indicating a worse prognosis

Gleason score ≥8 at diagnosis

Measurable Disease per Independent Radiological Review (IRR)

Bone

Nodal

Visceral

Participants may be counted in more than one category

Metastases site(s) by IRR

Prior Therapies for CRPC

Abiraterone acetate

Apalutamide

Enzalutamide

Docetaxel for hormone-sensitive prostate cancer

Prior therapy (2nd generation androgen receptor pathway inhibitor (ARPI) or docetaxel only)

Intent-to-Treat (ITT) Population included all randomized participants (participants with breast cancer gene \[BRCA\] mutated metastatic castration-resistant prostate cancer \[mCRPC\] and participants with ataxia- telangiectasia mutated serine/threonine kinase \[ATM\] mutated mCRPC).

Medical Information Department

Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration

ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC).

Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined

Interim Overall Survival in Participants With a BRCA Alteration

Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined

ITT Population with BRCA mutated mCRPC and measurable disease at baseline.

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

ITT Population included all randomized participants (participants with BRCA mutated mCRPC and participants with ATM mutated mCRPC) with measurable disease at baseline.

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

ITT Population with BRCA mutated mCRPC and measurable disease at baseline. 'Overall number of participants analyzed' = participants with objective response.

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

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.

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

PSA Response in Participants With a BRCA Alteration

PSA Response in Participants With a BRCA or ATM Alteration Combined

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.

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

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.

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

Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration

Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined

ITT Population with BRCA mutated mCRPC. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P

BPI-SF Pain Score

BPI-SF Interference Score

ITT Population with BRCA mutated mCRPC. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable for specified category.

Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF

Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L

Safety Population with at least 1 PK sample collected.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency	NCT02975934	Metastatic Cast...	Rucaparib Abiraterone ace...	18 Years -	pharmaand GmbH
A Study of Rucaparib Versus Physician's Choice of Therapy in Participants With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency	NCT02975934	Metastatic Cast...	Rucaparib Abiraterone ace...	18 Years -	pharmaand GmbH

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