Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer

Primary Objective - Determine overall response rate (ORR) in patients treated with CNP

Secondary Objective(s)

• Determine progression-free survival (PFS), and disease control rate (DCR) in patients treated with CNP.
• Determine duration of response in patients treated with CNP.
• Determine safety/tolerability of CNP.

Correlative Endpoints

• Identify pathologic and genomic correlates of response to CNP.

Study design including dose escalation / cohorts This is prospective pilot clinical trial of CNP in up to 30 patients with mTNBC

Inclusion criteria

• Subjects must have histologically or cytologically confirmed metastatic triple negative breast cancer
• Subjects must have received no more than 2 prior therapies for this disease
• ECOG Performance Status 0-1
• Subjects must have normal organ and marrow function as defined below:

• Hemoglobin ≥ 10.0 g/dl
• Absolute neutrophil count ≥ 1,000/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin within normal institutional limits
• AST (SGOT) ≤ 2.5 X institutional upper limit of normal
• ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
• Serum creatinine ≤ 1.5 normal institutional limits
• Life expectancy of 12 weeks or more
• Subjects must have the ability to understand and the willingness to sign a written informed consent document
• Subjects must have measurable disease per RECIST v1.1
• Subjects must be willing to undergo a preliminary biopsy of a metastatic focus for research purposes. A second post-treatment biopsy will be offered but will not be mandated

Exclusion criteria

• Prior treatment toxicities have not resolved to ≤ Grade 1 according to NCI CTCAE Version 4.0 (except for alopecia and neuropathy)
• Subjects receiving any other investigational agents
• Subjects with radiographically stable treated brain metastases are eligible but must not have been on steroid therapy for at least 4 weeks
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, carboplatin, pembrolizumab, or other agents used in this study
• Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women are excluded from this study
• Patients with conditions requiring immunosuppressive medications or chronic infections (including HIV infection, hepatitis B and C)
• Patients with chronic autoimmune disease
• Patients with prior therapy with antibodies that modulate T-cell function (e.g., anti-PD-1, anti-PD-L1)
• Patients with evidence of active, non-infectious pneumonia
• Patients active infection requiring intravenous systemic therapy
• Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with requirements of the trial
• Patients who have received a live vaccine within 30 days prior to the first dose of pembrolizumab
• Patients with a known additional malignancy that is progressing or requires active treatment (within the last 5 years). Exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy
• Patients who have received monoclonal anti-cancer antibody within 4 weeks of first dose of study drugs
• Patients who have received chemotherapy, small molecule targeted therapy or radiation within the 2 weeks of first dose of study drugs
• Patients who have participated in MK-3475 Merck studies
• Patients with carcinomatous meningitis