Introduction
tumor, melanoma, breast cancer, renal cell cancer, lung cancer, hepatocellular cancer, herpes simplex
VIRUS, TUMOR, MELANOMA, BREAST CANCER, MALIGNANCIES, HER2-NEGATIVE BREAST CANCER, ADVERSE EVENT, LOCALLY ADVANCED BREAST CANCER, HERPES SIMPLEX
Neoadjuvant therapy is a frequently employed strategy for the treatment of patients with high-risk localized breast cancer because it can improve resectability and serve as a benchmark for response to therapy. Moreover, patients with a pathologic complete response (pCR) after neoadjuvant therapy have longer event-free and overall survival (OS; refs. Nivolumab, an anti-PD-1 mAb, and ipilimumab, an anti–CTL-associated antigen 4 (CTLA-4) mAb, are immune checkpoint inhibitors that have shown antitumor activity in several malignancies, including melanoma, renal cell cancer, lung cancer, and hepatocellular cancer (Talimogene laherparepvec (T-VEC) is a genetically engineered herpes simplex virus type 1 (HSV-1), which lacks genes essential for replication in normal tissue and is still sensitive to HSV-1–directed drugs like acyclovir (We reasoned that intralesional injection of T-VEC would induce local immune activation that would prime the activity of combined immune checkpoint blockade with nivolumab and ipilimumab, resulting in tumor responses in patients with locally advanced breast cancer. Therefore, we designed a phase Ib trial with a chemotherapy-free regimen of nivolumab and ipilimumab combined with intralesional T-VEC for neoadjuvant treatment of localized, operable HER2-negative breast cancer. The primary objective was to evaluate the safety and adverse event profile of immunotherapy combined with T-VEC in patients with localized, HER2-negative breast cancer.