A Study to Investigate the Biological Effects of Saruparib (AZD5305), Darolutamide, and in Combination in Men With Newly Diagnosed Prostate Cancer.

Inclusion Criteria:

• male participants >/= 18 years old

• participants deemed suitable for radical prostatectomy

• participants with localised prostate cancer with unfavourable intermediate/high/veryhigh risk eligible for prostatectomy

• adequate organ and marrow function as per protocol

• capable of giving signed informed consent

• For participants participating in the Optional Genetic Research Only: Provision ofsigned and dated written Optional Genetic Research Information

• Available FFPE diagnostic tumour biopsy samples

• Participants must use a condom (with spermicide) from screening to 6 months afterscreening and refrain from fathering a child or donating sperm

Exclusion Criteria:

• As judged by the Investigator, any evidence of severe or uncontrolled systemicdiseases, including, active bleeding diatheses, or active infection including HepB,hepatitis C and HIV. Screening for chronic conditions is not required.

1. Active HBV is defined by a known positive HBsAg result. Participants with apast or resolved HBV infection (defined as the presence of HepB antibody andabsence of HBsAg) are eligible.

2. Participants positive for HCV antibody are eligible only if PCR is negative forHCV RNA.

• Participants with any known predisposition to bleeding (eg, active pepticulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabeticretinopathy).

• Participants with history of MDS/AML or with features suggestive of MDS/AML (asdetermined by prior diagnostic investigation). In case there is no Clinical MDS/AMLsuspicion, no specific screening for MDS/AML (by bone marrow/bone biopsy) isrequired.

• Prior malignancy within 3 years of screening whose natural history, in theInvestigator's opinion, has the potential to interfere with safety and efficacyassessments of the investigational regimen.

• Concomitant use of drugs that are known to prolong or shorten QT and have a knownrisk of TdP.

• Any of the following cardiac criteria:

1. Mean resting corrected QT interval (QTcF) > 450 milliseconds or QTcF < 340milliseconds obtained from triplicate ECGs and averaged, recorded within 5minutes.

2. Any factors that increase the risk of QT prolongation, shortening or risk ofarrhythmic events such as hypokalaemia, congenital long or short QT syndrome,family history of long QT syndrome, familial short QT syndrome or unexplainedsudden death under 40 years of age or any concomitant medication known toprolong or shorten the QT interval.

3. Any clinically important abnormalities in rhythm, conduction or morphology ofresting ECG eg, complete left bundle branch block, second or third degreeatrioventricular block and clinically significant sinus node dysfunction nottreated with pacemaker.

• Other CVS diseases as defined by any of the following:

1. Symptomatic heart failure (as defined by NYHA class ≥ 2).

2. uncontrolled hypertension.

3. hypertensive heart disease with significant left ventricular hypertrophy.

4. History of acute coronary syndrome/acute myocardial infarction, unstable anginapectoris, coronary intervention procedure with percutaneous coronaryintervention or coronary artery bypass grafting within 6 months prior toscreening.

5. cardiomyopathy of any aetiology.

6. presence of clinically significant valvular heart disease.

7. history of atrial or ventricular arrhythmia requiring acute treatment;participants with atrial fibrillation and optimally controlled ventricular rate (heart rate < 100 bpm) are permitted.

8. transient ischaemic attack, or stroke within 6 months prior to screening.

9. participants with symptomatic hypotension at screening.

• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability toswallow the formulated product or previous significant bowel resection that wouldpreclude adequate absorption of Saruparib (AZD5305).

• History of prior malignancy, treated with chemotherapy, biological therapy,radiation therapy, androgens, thalidomide, immunotherapy, or other anticancer agentwithin 3 years of screening. Previously localised surgically treated malignancy isacceptable, if no evidence of recurrence.

• Known allergy or hypersensitivity to investigational product(s) or any of theexcipients of the investigational product(s).

• Prior treatment with any systemic or localised anti-cancer treatment for thelocalised prostate cancer.

• During the 4 weeks prior to the first dose, receiving immune modulatory agentsincluding but not limited to, continuous corticosteroids at a dose of > 10 mgprednisone/day or equivalent.

• Concomitant use of medications or herbal supplements known to be:

1. Strong CYP3A4 inducers/inhibitors (applies for Saruparib (AZD5305) andSaruparib (AZD5305) + darolutamide arms)

2. Strong or moderate CYP3A4 and P-glycoprotein inducers (applies to darolutamidearm and Saruparib (AZD5305) + darolutamide arm) This is including, but notlimited to, the prohibited medications listed in CSP Appendix G, or inabilityto stop the use thereof, at least 21 days or at least 5 half-lives (whicheveris longer) before the first dose of study treatment until 30 days after thelast dose of study treatment.

• Treatment with any investigational agents or study interventions from a previousclinical study within 5 half-lives or 3 weeks (whichever is longer) of the firstdose of study treatment.

• Participants with contraindication to darolutamide for treatment arms

• Unable to comply with the visits and assessments.

• In the opinion of the Investigators should not be included in this study.

No treatment arm only: if any participant meets exclusion 4, 9 or 11, they are not to be included in the study.