Critères d'inclusion : 1.Provision of informed consent prior to any study specific procedures
2.Patients must be male or female ≥18 years of age.
3.Progressive cancer at the time of study entry with a life expectancy of ≥16 weeks
4.Histologically or cytologically confirmed TNBC with evidence of metastatic disease as per ASCO-CAP HER2 guideline recommendations 2013
5.Patients must have received at least 1 and no more than 2 prior lines of treatment for metastatic disease with an anthracycline (eg, doxorubicin, epirubicin) and/or a taxane (eg, paclitaxel, docetaxel) unless contraindicated, in either the neo-adjuvant, adjuvant or metastatic setting.
6.Confirmed presence of qualifying HRR mutation or absence of any HRR mutation in tumour tissue by the Lynparza HRR assay.
7.At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging [MRI] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
8.Patients must have normal organ and bone marrow function measured within 28 days prior to randomisation as defined by protocol
9.ECOG PS 0-1 within 28 days of randomisation.
10.Patients must be willing to comply with the protocol requirements
Critères de non-inclusion : 1. Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy within 21 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 21 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to study treatment.
2. More than 2 prior lines of cytotoxic chemotherapy for metastatic disease.
3. Previous randomisation in the present study.
4. Previous treatment with a PARP inhibitor (including olaparib) or other DDR inhibitor (unless treatment was for less than 3 weeks duration and at least 12 months have elapsed between the last dose and randomisation. Patients that did not tolerate prior treatment are excluded).
5. Exposure to a small molecule IP within 30 days or 5 half-lives (whichever is longer) prior to randomisation.The minimum washout period for immunotherapy shall be 42 days.
6. Patients with MDS/AML or with features suggestive of MDS/AML.
7. Patients with second primary cancer, EXCEPTIONS: adequately treated non melanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years prior to study entry.
8. Mean resting corrected QTc interval using the Fridericia formula (QTcF) >470 msec/female patients and >450 msec for male patients or congenital long QT syndrome.
9. Any of the protocol specified cardiac diseases currently or within the last 6 months defined by New York Heart Association (NYHA) ≥ Class 2:
10. Concomitant use of known strong cytochrome P (CYP) 3A inhibitors or use of known strong or moderate CYP3A inducers.
11. Persistent toxicities (≥ CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE grade 2 peripheral neuropathy.
12. Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
13. Immunocompromised patients, eg,human immunodeficiency virus (HIV) patients.
14. Patients with known active hepatitis (B or C).
15. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non malignant systemic disease or active, uncontrolled infection.
16. Patients with symptomatic uncontrolled brain metastases.
17. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
18. Patients with a known hypersensitivity to olaparib, AZD1775, AZD6738, or any of the excipients of the products.
19. Pregnant or breast feeding women.