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

Inclusion Criteria

• Age ≥ 21 years of age
• ECOG performance status 0-2
• 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 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 51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
• 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.
• 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.
• Subjects willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examination.
• 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

• 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.
• Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
• 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.
• Is taking chronic systemic steroids in doses > 10mg of prednisolone or equivalent within 7 days prior to the first dose of trial treatment.
• Previous treatment with PARP inhibitors including olaparib.
• 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.
• Known active central nervous system metastasis and / or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they have:
• 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**,
• No evidence of new or enlarging brain metastases; any neurologic symptoms should have returned to baseline,
• 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.
• History and/or confirmed pneumonitis, or extensive bilateral lung disease on high resolution/spiral CT scan.
• Patient