Pembrolizumab and Carboplatin in Treating Patients with Circulating Tumor Cells Positive Metastatic Triple-Negative Breast Cancer

Inclusion Criteria

• Patients must be hormone receptor (HR) negative and HER-2 negative (TNBC) metastatic breast cancer and have not received prior chemotherapy for metastatic disease and should have been exposed to anthracyclines and taxane in neoadjuvant and adjuvant settings (first-line); demonstrated HER-2 negative MBC (0 or 1+ by immunohistochemistry [IHC] or non-amplified by fluorescence in situ hybridization [FISH]) according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPA) guidelines
• Patients should be either stage IV de-novo or develop recurrence after completion of neoadjuvant/adjuvant therapy
• Patients must be CTC positive (defined as CTCs >= 5)
• Be >= 18 years of age on day of signing informed consent
• Have measurable disease based on RECIST 1.1
• Be willing to provide archival tissue (if available) for correlative studies * Note: The archived tumor tissue specimens may be from metastatic tumor specimen (first choice); in alternative, we can consider tissue from prior surgery or from prior diagnostic biopsy (second choice); unavailability of archived tissue will not render subject ineligible for study
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance status
• Demonstrate adequate organ function, all screening labs should be performed within 14 days prior to registration
• Absolute neutrophil count (ANC) >= 1,500 /mcL (should be performed within 14 days prior to registration)
• Platelet >= 100,000 / mcL (should be performed within 14 days prior to registration)
• Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (should be performed within 14 days prior to registration)
• Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN (should be performed within 14 days prior to registration)
• Albumin >= 2.5 mg/dL (should be performed within 14 days prior to registration)
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (should be performed within 14 days prior to registration)
• Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (should be performed within 14 days prior to registration)
• For patients with a known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a known history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Female subject of childbearing potential (FOCBP) should have a negative urine or serum pregnancy within 7 days prior to registration; and must be repeated within 3 days (72 hours) prior to first dose of study drug; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * (Note: A FOCBP is any woman [regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice] who meets the following criteria: ** Has not undergone a hysterectomy or bilateral oophorectomy ** Has had menses at any time in the preceding 12 consecutive months [and therefore has not been naturally postmenopausal for > 12 months])
• Female subjects of childbearing potential must be willing to use an adequate method of contraception; contraception must be used 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
• 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 * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
• Be willing and able to provide written informed consent/assent for the trial

Exclusion Criteria

• Histologically or cytologically confirmed HER2-positive (3+ by IHC or amplified by FISH) according to ASCO/CAP guidelines * Note: A HER2 result of 2+ by ICH is equivocal and requires a reflex test (same specimen using the alternative test) or new test (new specimen, if available, using same or alternative test)
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device =< 28 days of registration
• Patients who had prior carboplatin in the metastatic setting are not eligible * Note: Prior carboplatin as neoadjuvant or adjuvant treatment is permitted
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy =< 7 days prior to registration
• Has a known history of active TB (bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• 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 baseline) from adverse events (AEs) due to agents administered more than 28 days earlier
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 14 days prior to registration or who has not recovered (i.e., =< grade 1 or at baseline) from AEs due to a previously administered agent * Note: Subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention and at least two weeks have to pass prior to starting therapy
• Has known additional malignancy that progressed or required treatment within last 5 years; 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 that has been adequately treated
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days prior to registration and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to registration; this exception does not include known carcinomatous meningitis which is excluded regardless of clinical stability * Note: steroids as premedication are permitted in this study
• 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 systemic treatment
• Patients who have evidence of active, noninfectious pneumonitis or have a history of severe pneumonitis that required treatment with steroids are not eligible for this study
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
• Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has received a live vaccine within 30 days of planned start of study therapy. Administration of killed vaccines is allowed * 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