Pembrolizumab in Combination with Binimetinib in Patients with Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer

Purpose: Activation of the RAS/MAPK pathway is associated patients who achieved objective responses, 80% had a duration of with reduced tumor-infiltrating lymphocytes and poor outcomes response >12 months and ongoing even after stopping treatment in triple-negative breast cancer. Previous studies demonstrated (5.4–69.0 months). Patients with PD-L1–positive tumors (modified that inhibition of the MAPK pathway with a MEK inhibitor is proportion score ≥10) were more likely to respond with an ORR of synergistic with immune checkpoint inhibitors. 66.7%. However, clinical benefit was observed in 25% of patients Patients and Methods: We conducted a phase I/II trial of with PD-L1–negative tumors. Consistent with preclinical studies, pembrolizumab and binimetinib in patients with metastatic four of six patients with clinical benefit had either increased PD-L1 triple-negative breast cancer with ≤3 prior lines of therapy. There or decreased p-ERK expressions in serial circulating cancer-were two dose levels (DL) with binimetinib at 45 mg at DL 0 and associated macrophage-like cells after starting binimetinib. 30 mg at DL -1. Conclusions: Pembrolizumab and binimetinib at 30 mg are safe Results: The recommended phase II dose was the standard with manageable toxicities. Promising activity was observed in dose of pembrolizumab with binimetinib 30 mg twice daily. The patients without liver metastases. Future larger clinical trials are objective response rate (ORR) was 30.4%, with a numerically warranted to further evaluate the efficacy of this chemotherapy-free higher ORR in patients without liver metastasis at 45.5%. Among combination.