Investigation of Anti-tumour Effect and Tolerability of the PARP Inhibitor 2X-121 in Patients With Metastatic Breast Cancer Selected by the 2X-121 DRP

Inclusion criteria

• Signed informed consent form.
• Age 18 years or older.
• Histologically or cytological documented mBC (independent of hormone receptor, HER2 status and BRCA1 or 2 status) relapsed in 2 or more different prior therapies.
• Measurable disease by CT scan or MRI.
• With a drug response prediction (DRP) for 2X-121 with an outcome measured as being in the upper 20% likelihood of response.
• Prior chemotherapy or hormone therapy for metastatic breast cancer is allowed.
• Performance status of ECOG <= 1
• Recovered to Grade 1 or less from prior surgery or from acute toxicities of prior radiotherapy, or from treatment with cytotoxic, hormonal or biologic agents).
• >= 2 weeks must have elapsed since any prior surgery or therapy with G-CSF and GM-CSF.
• Patients with intracranial disease must be on stable or decreased level of steroid therapy (e.g. dexamethasone) for at least 7 days prior to baseline MRI. Non-enzymatic inducing ant-epileptic drugs are allowed.
• Adequate conditions as evidenced by the following clinical laboratory values:

• Absolute neutrophils count (ANC) >= 1.5 x 10E9/L
• Haemoglobin is at least 4.6 mmol/L
• Platelets >= 100 x 10E9 /L
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 x ULN*
• Serum bilirubin <= 1.5 ULN
• Alkaline phosphatase <= 2.5 x ULN*
• Creatinine <= 1.5 ULN
• Blood urea within normal limits
• Creatinine clearance within normal limits. *In case of known liver metastases with ALT and AST <= 5 x ULN and/or alkaline phosphatase <= 5 x ULN. Patients who do not conform to the transaminase and/or alkaline phosphatase inclusion criteria, but who by the PI are considered in good PS and otherwise eligible for inclusion, and where the transaminase and/or alkaline phosphatase levels are considered elevated due to other reasons than deteriorated lever capacity, may be considered for inclusion based on conferred agreement between PI and sponsor.
• Life expectancy equal or longer than 3 months.
• Sexually active females of child-producing potential must use adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception) for the study duration and at least six months afterwards.

Exclusion criteria

• - Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period.
• Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study.
• Previous treatment with PARP inhibitors
• Any active infection requiring parenteral or oral antibiotic treatment.
• Has known HIV positivity.
• Has known active hepatitis B or C.
• Has clinical significant (i.e. active) cardiovascular disease:

• Stroke within <= 6 months prior to day 1
• Transient ischemic attach (TIA) within <= 6 months prior to day 1
• Myocardial infarction within <= 6 months prior to day 1
• Unstable angina
• New York Hart Association (NYHA) Grade II or greater congestive heart failure (CHF)
• Serious cardiac arrhythmia requiring medication
• Mental status is not fit for clinical study or CNS disease including symptomatic epilepsy.
• Other medications or conditions, including surgery, that in the Investigator's opinion would contraindicate study participation of safety reasons or interfere with the interpretation of study results
• Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of 2X-121.
• Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
• Female patients who are pregnant or breast-feeding (pregnancy test with a positive result before study entry)