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