Phase II Multicenter Study of Durvalumab and Olaparib in Platinum tReated Advanced Triple Negative Breast Cancer (DORA)

Inclusion Criteria: 1. Age ≥ 21 years of age 2. ECOG performance status 0-2 3. Inoperable locally advanced or metastatic breast cancer not amenable to resection with curative intent and histologically confirmed to be estrogen receptor (ER) negative, progesterone receptor (PR) negative, and HER2 negative: * ER negative status is defined as \< 1% tumor cells positive for ER by immunohistochemistry (IHC), irrespective of staining intensity * PR negative status is defined as \< 1% tumor cells positive for PR by IHC, irrespective of staining intensity NOTE: Enrollment is permitted for ER/PR low-expression subjects (defined as ≤ 10%) who are expected to benefit from this trial at the investigator's discretion. * HER2 negative status is determined by: * IHC 1+, as defined by incomplete membrane staining that is faint/barely perceptible and within \> 10% of invasive tumor cells, or * IHC 0, as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within ≤ 10% of the invasive tumor cells, or * FISH negative based on: * Single-probe average HER2 copy number \< 4.0 signals / cell, or * Dual-probe HER2/CEP17 ratio \< 2.0 with an average HER2 copy number \< 4.0 signals / cell 4. Minimum six 1-weekly doses or three 3-weekly doses of platinum chemotherapy (monotherapy or combination therapy at investigator's discretion) with stable disease (SD), partial response (PR) or complete response (CR) to the platinum therapy as assessed by investigator. 5. Has received no more than 2 prior chemotherapy regimens for metastatic breast cancer including current platinum based chemotherapy. 6. Able to provide a representative formalin-fixed, paraffin embedded tumour specimen archival or fresh tissue for correlative studies and biomarker analysis. 7. Hemoglobin ≥ 9.0 g/dL and no blood transfusions in the 28 days prior to study entry. Absolute neutrophil count ≥1,500/mm3. Platelet count ≥100 x 10\^9/L. 8. Total bilirubin \<1.5 x the upper limit of normal (ULN) with the following exception: subjects with known Gilbert's disease who have serum bilirubin \<3 x ULN may be enrolled. 9. Aspartate transaminase (AST) and alanine transaminase (ALT) \<2.5 x ULN with the following exceptions: subjects with documented liver or bone metastases may have AST and ALT \<5 x ULN. 10. Alkaline phosphatase (ALP) \<2 x ULN (\<5 x ULN in subjects with known liver involvement and \<7 ULN in subjects with known bone involvement). 11. Serum creatinine \<1.5 x ULN or creatinine clearance \>51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. 12. For subjects of childbearing potential, agreement (by both subject and partner) to use two effective forms of contraception, including surgical sterilization, reliable barrier method, birth control pills, contraceptive hormone implants, or true abstinence and to continue its use for the duration of the study and for 3 months after last dose of study treatment. 13. Subjects of childbearing potential should have a negative urine or serum pregnancy test during their screening visit. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 14. Subjects willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examination. 15. For inclusion in genetic research, subjects must provide informed consent for genetic research collection of specimens to be stored at repository for future research. Exclusion Criteria: 1. Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of first dose of treatment. Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device. 2. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study. 3. Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, or similar treatment) is not considered a form of systemic treatment. 4. Is taking chronic systemic steroids in doses \> 10mg of prednisolone or equivalent within 7 days prior to the first dose of trial treatment. 5. Previous treatment with PARP inhibitors including olaparib. 6. Patients that have required discontinuation of treatment due to treatment-related toxicities from prior therapy with PD-1, PDL-1 or CTLA-4 inhibitors or previous history of immune-related grade 3 or 4 adverse event. 7. Known active central nervous system metastasis and / or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they have: 1. Stable brain metastases \[without evidence of progression by imaging (confirmed by computerized tomography {CT} scan if CT used at prior imaging) for at least four weeks prior to the first dose of trial treatment\*\*, 2. No evidence of new or enlarging brain metastases; any neurologic symptoms should have returned to baseline, 3. Not used steroids for brain metastases in the 7 days prior to trial initiation. Taking chronic systemic steroids in doses ≤ 10mg of prednisolone is allowed. * This exception does not include carcinomatous meningitis, as subjects with carcinomatous meningitis are excluded regardless of clinical stability. 8. History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan. 9. Patients with suspected or confirmed myelodysplastic syndrome/acute myeloid leukemia. 10. History of another primary malignancy except for: 1. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence. 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ. 11. Major surgery within 2 weeks of starting the study, and subjects must have recovered from any effects of any major surgery. 12. Receipt of radiation therapy within 4 weeks prior to starting study drug(s). Limited field of radiation for palliation within 2 weeks of the first dose of study treatment is allowed provided: 1. The lung is not in the radiation field 2. Irradiated lesion(s) cannot be used as target lesions 13. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, active bleeding diatheses including any subjects known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness / social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent. 14. Subjects unable to swallow orally administered medication, and subjects with gastrointestinal disorders likely to interfere with absorption of the study medication. 15. Subjects requiring treatment with potent inhibitors or inducers of CYP3A4. 16. Pregnant or breast-feeding women. If breastfeeding can be stopped prior to study enrollment until 1 month after the last study dose, then the patient could be allowed to enter the study. 17. Immunodeficient subjects, eg, subjects who are known to be serologically positive for human immunodeficiency virus (HIV). 18. Received a live vaccine within 30 days of planned start of study therapy. 19. Subjects with a known hypersensitivity to olaparib or durvalumab, or any of the excipients of the product. 20. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) 21. History of allogeneic organ transplant 22. Active bleeding diatheses 23. Patients with known active hepatic disease (ie, Hepatitis B or C) 24. Known history of previous clinical diagnosis of tuberculosis.