Overview

This is a single center non-blinded randomized multi-cohort non-comparative phase II trial with a Simon's two-stage design.

Eligibility

Inclusion Criteria:

• Metastatic or incurable locally advanced triple negative breast cancer (ER < 10%, HER2 IHC 0,1+ or 2+ with no amplification)
• Metastatic lesion accessible for histological biopsy
• 18 years or older
• Maximum of three lines of chemotherapy for metastatic disease and with evidence of progression of disease. Treatment with low-dose doxorubicin in the palliative setting is not allowed.
• WHO performance status of 0 or 1
• Measurable or evaluable disease according to RECIST 1.1
• Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year
• Subjects with brain metastases are eligible if these are not symptomatic and free of progression of at least 4 weeks
• A maximum dosage of 360 mg/m2 of anthracyclines and no previous anthracycline-related cardiac toxicity. In case of radiation in the cardiac area, hypertension, diabetes mellitus or hypercholesterolemia, the left ventricular ejection fraction must be 50% or higher.
• Adequate bone marrow, kidney and liver function

Exclusion Criteria:

• uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
• known history of leptomeningeal disease localization
• history of having received other anticancer therapies within 2 weeks of start of the study drug
• history of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (>10 mgl daily prednisone equivalents) or chronic infections.
• prior treatment with immune checkpoint inhibitors.
• active other cancer
• history of uncontrolled serious medical or psychiatric illness
• current pregnancy or breastfeeding