Pembrolizumab With Carboplatin Compared to Carboplatin Alone in Breast Cancer Patients With Chest Wall Disease

Inclusion Criteria

• Advanced breast cancer with locally recurrent chest wall disease not amenable to surgical excision with curative intent.
• Distant sites of disease are allowed
• Prior radiation to the chest wall is not required
• The following disease subtypes are eligible:
• Triple negative disease (defined as ER = institutional lower limit of normal (LLN) using echo or multiple gated acquisition scan (MUGA).
• Any number of prior lines of therapy are allowed. a Prior platinum based therapy is allowed in the following settings:
• Treatment in the neoadjuvant and/or adjuvant setting without clear progression of disease.
• Treatment in the metastatic setting without clear progression of disease. b Neo/adjuvant treatment with a checkpoint inhibitor is allowed if the last treatment was at least 12 months from the diagnosis of metastatic disease.
• At least two weeks from last systemic therapy for breast cancer, with recovery of all treatment related toxicity to grade 1 or less. Subjects with =1,000 /microliter (mcL)
• Platelets>=100,000 / mcL
• Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine OR Measured or calculated* creatinine clearance (GFR can also be used in place of creatinine or CrCl) =60 mL/min for subject with creatinine levels > 1.5 X institutional ULN. Creatinine clearance should be calculated per institutional standard.
• Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin 1.5 ULN
• Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Albumin >2.5 g/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria

• Treatment with an investigational agent within 4 weeks of the first dose of treatment.
• A diagnosis of immunodeficiency or is currently receiving systemic steroid therapy at any dose or is receiving any other form of immunosuppressive therapy. Steroid therapy is not allowed within 7 days prior to the first dose of trial treatment. However, topical and intranasal corticosteroids are allowed, and not an exclusion for participation.
• Known active TB (Bacillus Tuberculosis). Patients with a distant history of tuberculosis that was appropriately treated and have no evidence of active infection are eligible to participate. Patients with a history of latent tuberculosis that was appropriately treated are also eligible to participate.
• Hypersensitivity to pembrolizumab or any of its excipients.
• Hypersensitivity to carboplatin or cisplatin
• 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: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of system