nivolumab + rigosertib

Nivolumab + rigosertib is an investigational combination therapy consisting of two distinct anticancer agents. Nivolumab is a monoclonal antibody that targets the programmed death-1 (PD-1) receptor, functioning as an immune checkpoint inhibitor to enhance T-cell mediated antitumor responses. Rigosertib is a small molecule inhibitor that disrupts RAS signaling pathways, specifically acting as a pan-RAS signaling inhibitor by competitively binding to RAS-binding domains and interfering with downstream oncogenic signaling. The combination has been studied primarily in patients with advanced or metastatic KRAS-mutated non–small cell lung cancer (NSCLC), particularly those who have progressed after standard therapies including prior immune checkpoint inhibitors. Early-phase clinical trials have shown the regimen to be well tolerated and have demonstrated preliminary evidence of efficacy, including partial responses in heavily pretreated patient populations[1][3][4][5][8]. The rationale for this combination lies in rigosertib’s potential to overcome resistance mechanisms to immune checkpoint blockade by modulating tumor cell surface molecules and enhancing immunogenicity.