naporafenib + rineterkib

Naporafenib + rineterkib is an investigational oral combination therapy consisting of two small molecule inhibitors targeting the MAPK pathway. Naporafenib (LXH254) is a type II pan-RAF inhibitor that selectively inhibits BRAF (including wild-type and V600-mutant forms) and CRAF kinases, thereby blocking RAF-mediated signaling without causing paradoxical activation in normal cells. Rineterkib (LTT462) is an ERK1/2 inhibitor that targets downstream effectors in the MAPK pathway. The combination aims to provide dual blockade of the MAPK cascade at different nodes to overcome resistance mechanisms seen with single-agent therapies. This regimen has been studied primarily in patients with advanced or metastatic KRAS- or BRAF-mutant non-small cell lung cancer (NSCLC) and NRAS-mutant unresectable/metastatic melanoma[1][2][5]. Clinical trials have demonstrated acceptable safety profiles for this combination, with common adverse events including skin toxicities and elevated lipase levels[1][2]. Antitumor activity has been observed particularly in NRAS-mutant melanoma, where partial responses and disease control have been reported; however, efficacy was limited in NSCLC despite on-target pharmacodynamic effects[1][5].

Other names

naporafenib and rineterkibLXH254 + LTT462