This is a Phase 1b/2 trial employing a Simon Two Stage design to evaluate the safety, feasibility, and efficacy (defined as 10% increase in Ki67+ peripheral CD8 T cells post-treatment) of a single pembrolizumab infusion with or without radiation boost prior to definitive surgery in patients with operable breast cancer. The study has four arms. Arms 1 and 2 differ by the order of radiation boost and pembrolizumab administration. In arm 3, patients will receive pembrolizumab alone. A minimum of 6 patients will be enrolled in the safety run-in portion of the study. An additional 30 patients will be enrolled once pembrolizumab with the combination radiation is considered feasible and additional funding is available. Arm 4 represents our control arm in which patients will follow usual care but will be consented for blood/tissue collection using a separate protocol (Penn IRB 801539).
The primary objective is to determine the feasibility of combining pembrolizumab with a single fraction radiation boost in patients with early/ operable breast cancer. The secondary objectives are to assess clinical response on pre- and post-treatment clinical, imaging, and histology exams, and to assess immune response on pre and post treatment blood and tissue samples by tracking change in Ki67 + CD8 T cells in peripheral blood and in extent of tumor infiltrating lymphocytes