VIC-1911 is a novel, highly selective, orally active, small molecular inhibitor of aurora kinase A (AURKA). AURKA gene amplification/overexpression is reported in multiple tumors, including NSCLC. Inhibition of AURKA with VIC-1911 has demonstrated monotherapy activity in KRAS G12C-mutant human NSCLC cells with intrinsic and acquired resistance to the G12C inhibitor sotorasib. Furthermore, the combination of VIC-1911 and sotorasib showed synergy in the same cell lines. Interestingly, NSCLC cells with intrinsic resistance to sotorasib showed the most profound synergistic effects with the combination of VIC-1911 and sotorasib. These findings suggested that 1) AURKA activation led to intrinsic and acquired resistance to sotorasib in KRAS G12C-mutant NSCLC and 2) the combination of VIC-1911 and sotorasib may be a potential therapeutic approach for KRAS G12C-mutant patients with intrinsic and acquired resistance to sotorasib. In vivo data suggest that sotorasib and adagrasib are synergistic in combination with VIC-1911 in humans KRAS G12Cmutant NSCLC cell line xenograft models.
Additionally, to live studies have demonstrated the synergy of VIC-1911 plus sotorasib compared to their respective monotherapies in KRAS G12Cmutant NSCLC xenograft models and a KRAS G12C-mutant PDX model. The combination of VIC-1911 plus sotorasib may be more active than sotorasib alone in KRAS G12CNaive mutant NSCLC for G12C inhibitors.
“We now have two approved KRAS G12C inhibitors, sotorasib and adagrasib, available to treat our patients with KRAS G12C-mutated NSCLC,” said Sarah Goldberg, MD, Study Chair. “While response rates are considered good for patients naïve to KRAS G12C inhibitor therapy, more than 50% of patients have primary resistance and do not respond. Furthermore, many patients who respond quickly develop acquired resistance and relapse within months. With this new dual-target approach combining AURKA and KRAS G12C inhibitors, we hope to improve therapeutic outcomes for our patients with KRAS G12C-mutate NSCLC.”
“VIC-1911 is a potent and selective AURKA inhibitor. Preclinical studies strongly support the combination of AURKA inhibition with VIC-1911 and KRAS G12C inhibitors in KRAS G12C-mutant NSCLC,” said Thomas Myers, MD, Chief Medical Officer. “By utilizing this multi-targeted approach, we hope to provide a more effective therapeutic outcome for patients with KRAS G12C– Mutant NSCLC.
About VITRAC Therapeutics, LLC:
VITRAC is an integrated oncology research and development company with expertise in developing, managing and optimizing global pharmaceutical drug development programs from late discovery, translational research and clinical development to market authorization and post-marketing lifecycle management.