Neoadjuvant BO-112 and Hypofractionated Radiation Therapy with or without Nivolumab in Soft-Tissue Sarcoma: Preclinical and Phase I Results
Mené à l'aide de lignées cellulaires et de modèles murins puis mené sur 14 patients atteints d'un sarcome des tissus mous à haut risque de récidive, cet essai de phase I évalue la toxicité d'un traitement comportant une administration intratumorale néoadjuvante de BO-112 (un ARN double brin non codant synthétique sous forme de nanoplex capable d'activer des récepteurs du système immunitaire inné, notamment TLR3, RIG-I et MDA5) ainsi qu'une radiothérapie hypofractionnée, le tout en combinaison ou non avec le nivolumab
Neoadjuvant immune checkpoint blockade (ICB) and radiotherapy (RT) improve disease-free survival in select patients with soft-tissue sarcoma (STS). However, most STS are myeloid-rich and lack preexisting 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 14 patients with high-risk STS in a phase I 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 with standard RT. These immunologic changes coincided with encouraging disease control in a small, high-risk cohort, supporting further clinical development.
Cancer Discovery , article en libre accès, 2026