A Pilot and Phase II Study to Assess the Safety, Tolerability and Efficacy of Pembrolizumab Plus Chemotherapy in Metastatic Triple Negative Breast Cancer Patients

The goal of this study is to establish the safety and tolerability of pembrolizumab when administered in combination with either of two chemotherapy regimens (weekly paclitaxel or capecitabine) in unresectable/metastatic triple negative breast cancer (MTNBC) patients.

Inclusion Criteria:
• HER2-negative breast cancer (defined by immunohistochemistry (IHC) 0-1 (or) IHC 2 and in situ hybridization
• (ISH) HER2 / centromere on chromosome 17 (CEP17) < 2.0)ER and PR-negative breast cancer (defined by IHC<1%)
• Measurable metastatic or unresectable disease based on response evaluation criteria in solid tumors (RECIST) 1.1.
• Indicated for treatment with either weekly paclitaxel or oral capecitabine, as first or second-line chemotherapy in the metastatic/unresectable setting (as determined by the consenting investigator);
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained during screening. Archival tissue is acceptable if no intervening anti-neoplastic therapy has been administered, and if sufficient material is available for analysis

Exclusion Criteria:
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• 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 at baseline) from adverse events due to agents administered more than 4 weeks earlier. Denosumab is allowed.
• 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 and alopecia are an exception to this criterion and may qualify for the study.
• Has received the assigned chemotherapy regimen previously in the metastatic setting, or has received the assigned chemotherapy regimen previously in the (neo)adjuvant setting within 12 months of consent;
• 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 progressed or required active treatment in the last 5 years.
• 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has history of/active pneumonitis requiring treatment with steroids or history of/active interstitial lung disease.
• Has received prior therapy with an anti-programmed death 1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1), or anti-programmed death ligand 2 (anti-PD-L2) agent or has participated in a Merck-sponsored pembrolizumab study.

NOTE: Capecitabine cohort is now closed to enrollment
David Page, M.D.
Earle A Chiles Research Institute (EACRI)
Nikki Moxon
  • Cedar Sinai
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Franz Clinic