AMG 193 + pembrolizumab

AMG 193 + pembrolizumab is a combination therapy currently in clinical development for the treatment of advanced solid tumors, especially non-small cell lung cancer (NSCLC) with homozygous MTAP deletion. AMG 193 is an oral, CNS-penetrant, methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor that selectively induces synthetic lethality in MTAP-deleted tumor cells by robustly inhibiting PRMT5, leading to tumor cell death[1][2][4][7]. Pembrolizumab is a monoclonal antibody targeting PD-1, a checkpoint protein on T cells, and functions as a checkpoint inhibitor to enhance antitumor immune responses. The rationale for the combination is to target tumor cell survival through two mechanisms: synthetic lethality via PRMT5 inhibition (AMG 193) and immune checkpoint inhibition (pembrolizumab). The combination is being evaluated as an investigational regimen, with some study arms including additional chemotherapy agents such as carboplatin, pemetrexed, and paclitaxel[3][5]. Currently, AMG 193 + pembrolizumab is in phase I clinical trials, primarily sponsored by Amgen, and is tested for safety, tolerability, pharmacokinetics, and efficacy in metastatic or locally advanced MTAP-deleted thoracic tumors, including NSCLC[3][5][6].

Other names

AMG 193 + pembrolizumab