Trial to Evaluate Efficacy and Safety of Pembrolizumab and Gemcitabine in HER2-negative ABC

Inclusion Criteria

• The patient has signed and dated the informed consent document and it has been obtained before conducting any procedure specifically for the study.
• Female ≥ 18 years of age on day of signing informed consent.
• Histological/cytological confirmation of breast cancer with evidence of advanced disease, not amenable to resection or radiation therapy with curative intent.
• Documented luminal A, luminal B (HER2-negative) or triple negative disease by immunohistochemistry (IHQ) and/or in situ hybridization (FISH/CISH/SISH) based on local testing on the most recent tumour biopsy defined as follows:

Luminal A: tumour with positive oestrogen receptor (ER) status (≥1% of tumour cells with ER expression) and HER2-negative status (IHQ score 0/1+ or negative by in situ hybridization defined as a HER2/chromosome enumeration probe 17 (CEP17) ratio 1.5 x ULN

Coagulation:

International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.

Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.

• Prior treatment with anthracyclines and taxanes (unless clinically contraindicated) and two or more prior lines of hormone therapy in hormone receptor positive disease.
• At least 3 months life expectancy.
• Patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study drug/medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Patients of childbearing potential (see section 4.4. for definition) must be willing to use an adequate method of contraception as outlined in Section 4.4. - Contraception, for the course of the study through 120 days after the last dose of study medication.

Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria

• HER2-positive disease by immunohistochemistry or in situ hybridation (FISH-SISH-CISH).
• Patient is currently participating or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug/medication.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Patients with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has received prior therapy with an anti-Programmed death-1 (PD), anti-PD-L1, or anti-PD-L2 agent.
• Has received a live vaccine within 30 days of planned start of study therapy.

o Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed.

• Has hypersensitivity to pembrolizumab, gemcitabine or any of theirs excipients.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are s