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

• DOI: 10.1158/1078-0432.c.7819831
• Publication Date: 2025-05-15T13:11:43Z
• Authors: Saranya Chumsri; Joseph J. Larson; Emily Liu; Kathleen S. Tenner; Daniel Adams; Morgan T. Weidner; Amanda N. Arnold; Dana L. Haley; Pooja Advani; Kostandinos Sideras; Alvaro Moreno-Asp...; E. Aubrey Thompson; Edith A. Perez; Keith L. Knutson
• Keywords: Triple-negative breast cancer

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