daraxonrasib + TNG462

daraxonrasib + TNG462 is an investigational combination therapy under evaluation in a Phase 1/2 clinical trial for the treatment of metastatic pancreatic and lung cancers harboring both MTAP (methylthioadenosine phosphorylase) deletions and RAS mutations. Daraxonrasib is a RAS(ON) multi-selective inhibitor developed by Revolution Medicines, designed to target multiple active RAS mutant proteins. TNG462, developed by Tango Therapeutics, is a next-generation, potentially best-in-class MTA-cooperative PRMT5 (protein arginine methyltransferase 5) inhibitor that exploits synthetic lethality in cancers with MTAP loss. The combination seeks to simultaneously address two core oncogenic drivers—RAS signaling and PRMT5 dependency—potentially yielding synergistic antitumor effects specific to this genetically defined cancer population. The combination is currently being tested in patients with MTAP-deleted and RAS-mutant metastatic pancreatic or lung cancer[1][3][5][6].