GSK3326595 + pembrolizumab

GSK3326595 + pembrolizumab is a combination therapy under clinical investigation for select advanced solid tumors and non-Hodgkin lymphoma. GSK3326595 is an orally administered, potent, selective, reversible small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), while pembrolizumab is a monoclonal antibody immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1). The combined approach is hypothesized to enhance antitumor immune responses by combining the epigenetic modulation and antiproliferative effects of PRMT5 inhibition (GSK3326595) with immune activation through PD-1 blockade (pembrolizumab). Clinical trials tested the safety, tolerability, pharmacokinetics, and preliminary antitumor efficacy of this combination in patients with advanced cancers, particularly solid tumors and NHL. No responses were observed in the reported combination cohort, and development of GSK3326595 has faced challenges due to limited monotherapy efficacy[1][2][3][5].