Study on Olaparib Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (China Cohort)

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with therequirements and restrictions listed in the informed consent form and in the studyprotocol.

2. Provision of signed and dated, written informed consent form prior to any mandatorystudy specific procedures, sampling, and analyses.

3. For inclusion in i) the optional exploratory genetic research and ii) the optionalbiomarker research, patients must fulfill the following criteria:

• Provision of informed consent for genetic research prior to collection ofsample.

• Provision of informed consent for biomarker research prior to collection ofsample. If a patient declines to participate in the optional exploratory genetic research orthe optional biomarker research, there will be no penalty or loss of benefit to thepatient. The patient will not be excluded from other aspects of the study.

4. Patients must be ≥18 years of age (or ≥19 years of age in South Korea) at the timeof signing the informed consent form. For patients enrolled in Japan who are <20years of age, written informed consent should be obtained from the patient and fromhis legally acceptable representative.

5. Histologically or cytologically confirmed prostate adenocarcinoma.

6. Metastatic status defined as at least 1 documented metastatic lesion on either abone scan or a computed tomography(CT)/ magnetic resonance imaging (MRI) scan.

7. First-line metastatic castration-resistant prostate cancer (mCRPC).

8. Ongoing androgen deprivation with gonadotropin-releasing hormone analogue orbilateral orchiectomy, with serum testosterone <50 nanograms per decilitre (ng/dL) (<2.0 nanomoles per litre (nmol/L)) within 28 days before randomisation. Patientsreceiving androgen deprivation therapy (ADT) at study entry should continue to do sothroughout the study.

9. Candidate for abiraterone therapy with documented evidence of progressive disease.

10. Patients must have normal organ and bone marrow function measured within 28 daysprior to administration of study treatment.

11. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, with nodeterioration over the previous 2 weeks.

12. The participant has, in the opinion of the investigator, a life expectancy of atleast 6 months.

13. Prior to randomisation, sites must confirm availability of either an archivalformalin fixed, paraffin embedded (FFPE) tumour tissue sample, or a new biopsy takenduring the screening window, which meets the minimum pathology and samplerequirements in order to enable homologous recombination repair (HRR) statussubgroup analysis of the primary endpoint radiographic progression-free survival (rPFS). If there is not written confirmation of the availability of tumour tissueprior to randomisation, the patient is not eligible for the study.

14. Male patients must use a condom during treatment and for 3 months after the lastdose of olaparib+abiraterone when having sexual intercourse with a pregnant woman orwith a woman of childbearing potential. Female partners of male patients should alsouse a highly effective form of contraception if they are of childbearing potential.

Exclusion Criteria:

1. Has a known additional malignancy that has had progression or has required activetreatment in the last 5 years.

2. Patients with myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML) or withfeatures suggestive of yelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).

3. Clinically significant cardiovascular disease Association Class II-IV heart failureor cardiac ejection fraction measurement of <50% during screening as assessed byechocardiography or multigated acquisition scan.

4. Planned or scheduled cardiac surgery or percutaneous coronary interventionprocedure.

5. Prior revascularisation procedure (significant coronary, carotid, or peripheralartery stenosis).

6. Uncontrolled hypertension (systolic blood pressure (BP) ≥160 millimeters of mercury (mmHg) or diastolic blood pressure (BP) ≥95 millimeters of mercury (mmHg)).

7. History of uncontrolled pituitary or adrenal dysfunction.

8. Active infection or other medical condition that would make prednisone/prednisoloneuse contraindicated.

9. Any chronic medical condition requiring a systemic dose of corticosteroid >10milligrams (mg) prednisone/prednisolone per day.

10. Patients who are considered a poor medical risk due to a serious, uncontrolledmedical disorder, non-malignant systemic disease or active, uncontrolled infection.

11. Persistent toxicities (Common Terminology Criteria for Adverse Events [CTCAEs] grade >2) caused by previous cancer therapy, excluding alopecia.

12. Patients with brain metastases. A scan to confirm the absence of brain metastases isnot required.

13. Patients with spinal cord compression are excluded unless they are considered tohave received definitive treatment for this and have evidence of clinically stabledisease for 4 weeks.

14. Patients who are unevaluable for both bone and soft tissue progression

15. Patients who are unable to swallow orally administered medication and patients withgastrointestinal disorders likely to interfere with absorption of the studymedication.

16. Immunocompromised patients

17. Patients with known active hepatitis infection (ie, hepatitis B or C).

18. Any previous treatment with Polyadenosine 5'diphosphoribose [poly (ADP ribose)]polymerase (PARP) inhibitor, including olaparib.

19. Patients receiving any systemic chemotherapy or radiotherapy (except for palliativereasons) within 3 weeks prior to study treatment. Patients who receive palliativeradiotherapy need to stop radiotherapy 1 week before randomisation.

20. Any previous exposure to a Cytochrome P450 (CYP) 17 (17α-hydroxylase/C17,20-lyase)inhibitor (eg, abiraterone, orteronel).

21. Concomitant use of known strong Cytochrome P450 (CYP) 3A inhibitors (eg,itraconazole, telithromycin, clarithromycin, protease inhibitors boosted withritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir)or moderate CYP3A inhibitors (eg, ciprofloxacin, erythromycin, diltiazem,fluconazole, verapamil). The required washout period prior to starting studytreatment is 2 weeks.

22. Concomitant use of known strong Cytochrome P450 (CYP) 3A inducers (eg,phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine,carbamazepine, nevirapine or St John's wort) or moderate Cytochrome P450 (CYP) 3Ainducers (eg, bosentan, efavirenz or modafinil). The required period prior tostarting study treatment is 5 weeks for phenobarbital and enzalutamide and 3 weeksfor other agents.

23. Major surgery within 2 weeks of starting study treatment and patients must haverecovered from any effects of any major surgery.

24. Previous allogenic bone marrow transplant or double umbilical cord bloodtransplantation (dUCBT).

25. Participation in another clinical study with an investigational product orinvestigational medical devices within 1 month of randomisation.

26. History of hypersensitivity to olaparib or abiraterone, any of the excipients ofolaparib or abiraterone, or drugs with a similar chemical structure or class toolaparib or abiraterone.

27. Involvement in the planning and/or conduct of the study (applies to both AstraZenecaand Merck staff and/or staff at the study site).

28. Judgment by the investigator that the patient should not participate in the study ifthe patient is unlikely to comply with study procedures, restrictions andrequirements.

29. Previous randomisation in the present study.