Core Concepts
A reversible, tri-complex RAS inhibitor, RMC-7977, demonstrates potent activity against RAS-addicted tumors carrying various RAS genotypes, particularly KRAS codon 12 mutations, and can inhibit the growth of KRAS(G12C) cancer models resistant to existing KRAS(G12C) inhibitors.
Abstract
The content discusses the development and preclinical evaluation of a novel RAS inhibitor, RMC-7977, which has broad-spectrum activity against both mutant and wild-type RAS isoforms. Key highlights:
RAS oncogenes, particularly KRAS, are among the most frequently mutated genes in cancer, but existing KRAS(G12C) inhibitors only target a subset of KRAS-mutated cancers.
RMC-7977 is a reversible, tri-complex RAS inhibitor that can target the active state of various RAS isoforms, including KRAS, NRAS, and HRAS.
Preclinically, RMC-7977 demonstrated potent activity against RAS-addicted tumors carrying diverse RAS genotypes, especially those with KRAS codon 12 mutations (KRAS(G12X)).
Treatment with RMC-7977 led to tumor regression and was well-tolerated in various RAS-addicted preclinical cancer models.
RMC-7977 was also able to inhibit the growth of KRAS(G12C) cancer models that are resistant to existing KRAS(G12C) inhibitors due to restoration of RAS pathway signaling.
A related RAS(ON) multi-selective inhibitor, RMC-6236, is currently under clinical evaluation in patients with KRAS-mutant solid tumors.
Stats
RAS oncogenes are among the most frequently mutated genes in cancer.
KRAS(G12C) mutations account for only around 15% of KRAS-mutated cancers.
RMC-7977 demonstrated potent activity against RAS-addicted tumors carrying various RAS genotypes, particularly KRAS codon 12 mutations.
Quotes
"RAS(ON) multi-selective inhibitors can target multiple oncogenic and wild-type RAS isoforms and have the potential to treat a wide range of RAS-addicted cancers with high unmet clinical need."