OT-101 + pembrolizumab

**OT-101 + pembrolizumab** is an investigational combination therapy composed of OT-101 (Trabedersen), a synthetic antisense oligodeoxynucleotide targeting and inhibiting the expression of transforming growth factor-beta 2 (TGF-β2), and pembrolizumab, a humanized monoclonal antibody that inhibits programmed cell death 1 (PD-1). OT-101 antagonizes TGF-β2, a cytokine that can promote tumor immune evasion and progression, while pembrolizumab blocks PD-1, a checkpoint that restricts T-cell activation against tumors. The rationale for the combination is to synergistically enhance anti-tumor immunity by targeting two pathways of immune suppression. The main indications under clinical investigation are non-small cell lung cancer (NSCLC) with PD-L1 positivity and malignant pleural mesothelioma, particularly in patients previously treated with checkpoint inhibitors[1][2][3][5].