Neoadjuvant BO-112 en hypogefractioneerde bestraling met of zonder nivolumab bij wekedelensarcoom

Neoadjuvant immune checkpoint blockade (ICB) and radiation therapy (RT) improve disease-free survival in select patients with soft tissue sarcoma (STS). However, most STS are myeloid-rich and lack pre-existing T cells associated with ICB response. In preclinical models, we observed that intratumoral BO-112 (nanoplexed polyinosinic: polycytidylic acid (poly I:C)) engages myeloid cells that persist after RT, ultimately enhancing T cell-dependent tumor control. We evaluated BO-112 and hypofractionated RT, with or without nivolumab, in fourteen patients with high-risk STS in a phase 1 neoadjuvant trial. Consistent with its immunologic potency, the triple combination induced rare immune-related adverse events (myositis-myocarditis-myasthenia gravis spectrum), mitigated by BO-112 and nivolumab dose adjustment. BO-112 and RT reprogrammed tumor-associated myeloid cells toward antigen-presenting states, promoted clonal replacement by less exhausted T cells, and enhanced malignant cell depletion compared to standard RT. These immunologic changes coincided with encouraging disease control in a small, high-risk cohort, supporting further clinical development.