RMC-6236 is a noncovalent inhibitor of the GTP-bound state of multiple RAS variants, showing potent anticancer activity in RAS-driven cancers. It effectively inhibits RAS-GTP, leading to tumor regression in preclinical models and clinical trials. RMC-6236 demonstrated significant tumor control and objective responses in patients with advanced KRAS G12X lung and pancreatic adenocarcinoma. It is well-tolerated and effective across various RAS mutations, including KRAS G12C, G12D, and G12V. RMC-6236 inhibits RAS signaling, leading to sustained pathway inhibition and tumor regression in vivo. It showed broad antitumor activity in preclinical models of RAS-driven cancers, including NSCLC, PDAC, and colorectal cancer. RMC-6236 also demonstrated the ability to penetrate the blood-brain barrier and showed synergy with immune-checkpoint inhibitors. PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses in patients with RAS-driven tumors. RMC-6236 is currently being evaluated in a phase I/Ib clinical trial (NCT05379985) for the treatment of advanced solid tumors with KRAS G12X mutations. The compound showed durable antitumor activity, with significant improvements in progression-free survival and tumor regression in multiple preclinical models. RMC-6236's broad-spectrum activity and tolerability make it a promising therapeutic option for RAS-driven cancers.RMC-6236 is a noncovalent inhibitor of the GTP-bound state of multiple RAS variants, showing potent anticancer activity in RAS-driven cancers. It effectively inhibits RAS-GTP, leading to tumor regression in preclinical models and clinical trials. RMC-6236 demonstrated significant tumor control and objective responses in patients with advanced KRAS G12X lung and pancreatic adenocarcinoma. It is well-tolerated and effective across various RAS mutations, including KRAS G12C, G12D, and G12V. RMC-6236 inhibits RAS signaling, leading to sustained pathway inhibition and tumor regression in vivo. It showed broad antitumor activity in preclinical models of RAS-driven cancers, including NSCLC, PDAC, and colorectal cancer. RMC-6236 also demonstrated the ability to penetrate the blood-brain barrier and showed synergy with immune-checkpoint inhibitors. PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses in patients with RAS-driven tumors. RMC-6236 is currently being evaluated in a phase I/Ib clinical trial (NCT05379985) for the treatment of advanced solid tumors with KRAS G12X mutations. The compound showed durable antitumor activity, with significant improvements in progression-free survival and tumor regression in multiple preclinical models. RMC-6236's broad-spectrum activity and tolerability make it a promising therapeutic option for RAS-driven cancers.