Atezolizumab With Nab-paclitaxel for Patients With Triple-negative Stage IV Breast Cancer

Women aged ≥ 18 with biopsy proven Triple Negative Breast Cancer locally advanced or stage IV at diagnosis.

Inclusion Criteria:

• Women aged ≥ 18 years who have provided written informed consent
• Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
• No prior chemotherapy, experimental or targeted systemic therapy for inoperable locally advanced or metastatic TNBC. Prior chemotherapy (including taxanes) in the neoadjuvant or adjuvant setting is allowable if treatment was completed ≥12 months prior to enter the compassionate use program
• PD-L1-positive tumour status defined as PD-L1 expression ≥1% on tumour-infiltrating immune cells as percentage per tumour area, assessed by the Ventana PD-L1 (SP142) assay based on the status of the primary tumor and/or the biopsy of metastatic disease before starting the treatment. Samples should be assessed by a qualified laboratory and different assays are not acceptable
• Patients eligible for ongoing atezolizumab clinical trials from which they may benefit are excluded
• Eligible for taxane monotherapy (i.e., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control)
• ECOG performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Measurable disease, as defined by RECIST v1.1
• Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1)
• ANC ≥1500 cells/µL (without granulocyte colony-stimulating factor [G-CSF] support within 2 weeks prior to Cycle 1, Day 1);
• Lymphocyte count ≥500/µL; Platelet count ≥100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1);
• Hemoglobin ≥9.0 g/dL; AST, ALT, and alkaline phosphatase ≤2.5x the upper limit of normal (ULN), with the following exceptions:
• Patients with documented liver metastases: AST and ALT ≤5x ULN
• Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5x ULN
• Serum bilirubin ≤1.25x ULN (patients with known Gilbert disease who have serum bilirubin level ≤3x ULN may be enrolled)
• INR and aPTT ≤1.5x ULN (this applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose)
• Calculated creatinine clearance ≥30 mL/min
• Absence of a positive test for HIV, active hepatitis B or hepatitis C, active tuberculosis
• Absence of significant cardiovascular disease (New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to treatment start, unstable arrhythmias, or unstable angina. Patients with a known left ventricular ejection fraction (LVEF) \<40% will be excluded. Patients with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF \<50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate)
• No known untreated, symptomatic or corticosteroid-dependent brain metastases
• Patients with any history of immune deficiencies or autoimmune disease are excluded from the treatment. Possible exceptions could be autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone, controlled type 1 diabetes mellitus on a stable insulin dosing regimen, eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only
• Patients must not be administered systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to start the treatment
• Patients must agree not to receive live, attenuated vaccine (e.g., FluMist®) within 28 days prior to the first dose of study treatment (Cycle 1, Day 1), during treatment, or within 5 months following the last dose of atezolizumab
• No known hypersensitivity or allergy to nab-paclitaxel, to any of the excipients, to biopharmaceuticals produced in Chinese hamster ovary cells, or to any component of the atezolizumab formulation
• Pregnancy or lactation are general medical exclusion criteria from the treatment
• Women of child bearing potential must agree to either use a contraceptive method with a failure rate of ≤ 1% per year or to remain abstinent (refrain from heterosexual intercourse) during the treatment period and for at least 5 months after the last dose of atezolizumab or 1 month after the last dose of nab-paclitaxel, whichever is later. For definition of postmenopausal status see the study protocol
• Women of child bearing potential must have a negative serum pregnancy test result prior to start the treatment

Esclusion Criteria:

• Patients who have not completed 1 cycle of treatment