Evaluating the Efficacy and Safety of Bevacizumab, Carboplatin, Gemcitabine and Atezolizumab in Breast Cancer (BELLA)

• Drug: Atezolizumab
• Drug: Bevacizumab
• Drug: Gemcitabine
• Drug: Carboplatin

Inclusion Criteria:

1. Have provided written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment.
2. Male or female aged 18 years or over
3. Histologically documented triple negative breast cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs (TNBC) that is locally advancedat a late stage, far along or metastatic and is not amenable to resectionsurgical removal of tissue or part/all of an organ with curative intent Receptor status at study entry should correspond to the evaluation of the most recent biopsyremoval of a section of tissue to analyse for cancer cells as assessed locally TNBC for this study is defined as human epidermal growth factor receptor 2 (HER2)-negative by ASCO-CAP 2018 guidelines, and estrogen receptor (ER) expression < 10%, and progesterone receptor (PgR) expression < 10%
4. PD-L1 positive tumoura tissue mass that forms from groups of unhealthy cells or tumour-infiltrating lymphocyte-positive defined as:Immune cell PD-L1 expression ≥ 1% via SP142 assay via local or central lab OR Stromal TILs ≥ 5% by assessment on H&E stained tumour sections via local laboratory Note: Where possible, local or central testing should be done on the most recently available tumour specimena sample for investigating (e.g. blood, stools, urine, sputum etc.) and must have been obtained within 12 months prior to the date of consent.
5. Documented disease progression (e.g., with biopsy sample, pathologythe study of disease, or imagingtests that create detailed images of areas inside the body report) occurring within 12 months (<12 months) from the last treatment with curative intent, which meets one of the following:Date of the last chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells administration or Date of last curative intent adjuvant radiation therapyradiation therapy given after primary treatment, such as surgery, to reduce the risk of your cancer coming back or Date of the primary breast tumour surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence after neoadjuvant treatment, whichever occurred last
6. Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrenceto occur or happen again Note: Prior radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells for recurrent disease is permitted. There is no required minimum washout period for radiation therapy; however, patients should have recovered from the effects of radiation prior to registration.
7. Measurable disease, as defined by RECIST 1.1 Note: previously irradiated lesions may be considered as measurable disease only if disease progression has been unequivocally documented at that site since radiation.
8. Availability of a representative FFPE tumour block (preferred) or at least 25 unstained slides collected within 12 months prior to registration Note: An FFPE block/slides will not be required for cases where tumour tissuea group of cells that work together to perform a function was previously sent to the Central Laboratory for PD-L1 status testing in pre-screening following discussion with the CPI.Note: If a tumour sample taken within 12 months before registration is not available and a tumour biopsy is not clinically feasible, the primary surgical resection sample or the most recent FFPE tumour biopsy sample may be used.Note: Patients with fewer than 25 unstained slides (but no fewer than 17) may be eligible following discussion with the CPI.
9. Patients with an ECOG performance status 0-1 (see Appendix 1)
10. Life expectancy ≥ 12 weeks
11. Adequate haematologic and end-organ function, defined by the following laboratory results obtained within 7 days prior to registration:ANC ≥ 1.5×109/L (without G-CSF support within 2 weeks prior to registration) Lymphocyte count ≥ 0.5×109/L Platelet count ≥ 100×109/L (without transfusion within 2 weeks prior to registration) Haemoglobin ≥ 80 g/L (patients may be transfused or receive erythropoietic treatment to meet this criterion)AST and ALT ≤ 2.5 x the ULN, with the following exceptions:
    • Patients with documented liver metastases: AST and ALT ≤ 5× ULN Serum bilirubin ≤ 1.5× ULN
    • Patients with known Gilbert’s disease who have serum bilirubin level ≤ 3× ULN may be enrolled.

    Patients who are not receiving therapeutic anticoagulation: INR and aPTT ≤ 1.5× ULN. Patients who are receiving an anticoagulantmedication used to prevent or reduce blood clots; also known as blood thinners medicinal product must be on a stable anticoagulant regimen and have an INR which is not above the target therapeutic range during the 7 days prior to registration Calculated CrCl ≥ 30 mL/min (Cockcroft-Gault formula; see Appendix 2).

12. Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 6 months after the last dosethe amount of medication taken of study treatment (see section 7.11.1.1)
13. Women of child bearing potential must have a negative serum pregnancy test within 7 days prior to registration to the study
14. Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm as defined in section 7.11.1.2
15. Patient is willing and able to comply with the protocol for the duration of the study including undergoing biopsies, treatment, and scheduled visits and examination including follow up