Immune Induction Strategies to Improve Response to Immune Checkpoint Blockade in Triple Negative Breast Cancer (TNBC) Patients

In the first stage, 13 evaluable patients will be accrued per cohort. Evaluable is defined as: at least one administration of nivolumab and availability of paired biopsies for immunohistochemistry (for induction treatment cohorts pre-induction and pre-nivolumab biopsies).

If there are 1 or no responses observed in these 13 patients, the cohort will be stopped. Otherwise, 21 additional patients will be accrued for a total of 34.

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