Study of Neoadjuvant Olaparib Monotherapy and Olaparib and Durvalumab Combination in HER2 Negative BRCAm Breast Cancer

Inclusion Criteria:

* Males or Females ≥18 years
* Minimum body weight of 30 kg
* Capable of giving signed informed consent.
* Male and Female participants of childbearing potential must use effective methods of contraception
* Histologically confirmed, newly diagnosed, primary, operable, nonmetastatic invasive breast cancer with the following characteristics:

  --ER-negative or ER-low defined as IHC nuclear staining ≤10%
* HER2-negative (not eligible for anti-HER2 therapy) defined as:

  * IHC 0, 1+ without in situ hybridization OR
  * In situ hybridization non-amplified with ratio less than 2.0 OR
  * In situ hybridization average HER2 copy number \< 6 signals/cells
* Clinical TNM staging (per AJCC 8th Edition) as follows:

  * T1b (\>5 mm but ≤10 mm), N0, no known metastases (M0 or MX); OR
  * T1c (\>10 mm but ≤20 mm), N0, no known metastases (M0 or MX); OR
  * T1 (\>1 mm but ≤20 mm), N1, no known metastases (M0 or MX); OR
  * T2 (\>20 mm but ≤50 mm), N0, no known metastases (M0 or MX).).
* Documented deleterious or suspected deleterious mutation in BRCA1 or BRCA2 from local BRCA testing using either a germline or tumour test.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Participants must have adequate organ and bone marrow function
* Participant must be willing to undergo a baseline research biopsy prior to start of study treatment.
* Participant must be willing to have any leftover tumour tissue/FFPE from the diagnostic biopsy submitted for research purposes, if available.

Exclusion Criteria:

* Any evidence of other diseases (such as severe or uncontrolled systemic diseases or active, uncontrolled infections, including but not limited to, uncontrolled ventricular arrhythmia, uncontrolled hypertension, recent \[within 3 months\] myocardial infarction, uncontrolled major seizure disorder, renal transplant, active bleeding diseases, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan
* Refractory nausea and vomiting, chronic gastrointestinal disease likely to interfere with absorption of the study medication, inability to swallow the formulated product
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease for ≥5 years before the first dose of study intervention and of low potential risk for recurrence
* Participants with MDS or AML
* For higher risk (Cohort B) participants only: Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc), autoimmune pneumonitis, and autoimmune myocarditis
* Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody
* Known to have tested positive for human immunodeficiency virus unless currently on effective anti-retroviral therapy with an undetectable viral load within 6 months
* History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
* Participant must not have had any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation, or experimental therapy
* For higher risk (Cohort B) participants only: Prior exposure to anti-PD1, anti-PD-L1, or anti-CTLA4 agents (ICIs); OR an agent directed to other co-inhibitory or co-stimulatory T-cell receptors
* Any concurrent anticancer treatment
* Major surgical procedure (excluding placement of vascular access, local surgery of isolated lesions, or diagnostic staging) within 2 weeks of the first dose of study intervention
* For higher risk (Cohort B) participants only: Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
* Concomitant use of:

  * Known strong cytochrome P450 (CYP3A) inhibitors or moderate CYP3A inhibitors within 2 weeks prior to first dose of study intervention
  * Known strong CYP3A inducers or moderate CYP3A inducers .The required washout period prior to starting study therapy is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents