Olaparib with Cediranib or Ceralasertib for People with Advanced or Metastatic Breast Cancer and with a BRCA1 or BRCA2 Mutation

Assigned female at birth aged 18 years and older, who meet the following criteria:

All groups

• Have advanced or metastatic breast cancer that is HER2 negative with a BRCA1 or BRCA2 mutation. People with Estrogen receptor positive (ER+) breast cancer must have disease progression after previous endocrine therapy or these treatments are inappropriate.
• Have a life expectancy of more than 16 weeks
• Have a negative pregnancy test prior to study treatment and during study
• Use contraception 30 days prior to first treatment, for duration of the treatment, and at least 1 month after finishing the trial treatment
• Are willing to follow study schedule and instructions
• Have measurable diseases that can be detected with a CT or MRI scan
• Are willing to have a biopsy of the metastatic lesion before starting trial treatment
• Are willing to provide blood samples before starting treatment and at the end of the study
• Have been treated with any PARP inhibitor for at least 4 months
• Are able to swallow oral medication
• Do not have gastrointestinal illnesses that interfere with the absorption of medications
• Have adequate kidney and thyroid function

Group1

• Have adequate blood pressure (systolic blood pressure [SBP] =< 140 mmHg; diastolic blood pressure [DBP] =< 90 mmHg) that is checked within 2 weeks prior to the trial study and on maximum of 3 antihypertensive medications.

People under 18 years old and who:

• Had surgery, chemotherapy or radiation therapy within 3 weeks prior to start the study treatment
• Have had previous treatment with Ceralasertib and Cediranib
• Had severe side effects from previous treatment
• Have not recovered from side effects of treatments that they received more than 3 weeks
• Receive any other investigational treatment within the past 4 weeks
• Have untreated brain metastases, symptoms of brain metastases, or spinal cord compression
• Have received prior treatment with a drug known as a VEGF inhibitor
• Have history of allergic reactions to the ingredients of Olaparib or Cediranib or Ceralasertib
• Use complementary alternative medications including natural herbal products within 7 days prior to study treatment
• Have other invasive cancers within the past 5 years except skin cancer, breast cancer and cervix cancer on early stages
• Have other uncontrolled illness including heart disease, lung disease, active infection or a severe mental illness that would limit the ability to participate in the study
• Undergone surgery, open biopsy, or injury within 28 days prior to starting Cediranib
• Have bowel obstruction, something blocks your intestines and causes pain and discomfort, within 3 months before the study treatment
• Have significant bleeding within the last 1 month prior to study enrollment
• Have an infection in the stomach, within the 3 months prior to study enrollment
• Need intravenous (IV) fluids or total parenteral nutrition
• Have myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) 
• Have infections including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
• Have uncontrolled seizures
• Are pregnant or are breast feeding
• Have prior bone marrow transplant
• Have progression disease within 1 months after finishing platinum-based chemotherapy
• (Group1) Have a bleeding disease
• (Group2) diagnosis with ataxia telangiectasia (Louis-Bar syndrome)