VITRAC Therapeutics Initiates a Phase 1 Clinical Trial for the Treatment of Non-Small Cell Lung Cancer
VITRAC Therapeutics initiated a Phase 1 Study of VIC-1911 as monotherapy and in combination with Sotorasib for the treatment of KRAS G12C-mutant non-small cell lung cancer (NSCLC). The study is being performed at Yale Cancer Center with Sarah Goldberg, MD, MPH, as Principal Investigator (PI) and Study Chair; New York University Perlmutter Cancer Center, Vamsidhar Velcheti, MD, PI; University of California Davis Comprehensive Cancer Center, Jonathan Riess, MD, PI; University of Maryland Cancer Center, Katherine Scilla, MD, PI; Emory University Winship Cancer Center, Jennifer Carlisle, MD, PI.
VIC-1911 is a novel, highly selective, and orally active small molecular inhibitor of aurora kinase A (AURKA). AURKA gene amplification/overexpression is reported in multiple tumors, including NSCLC. AURKA inhibition with VIC-1911 demonstrated monotherapy activity in KRAS G12C-mutant human NSCLC cells with intrinsic and acquired resistance to the G12C inhibitor sotorasib. In addition, 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 both 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 suggests both sotorasib and adagrasib are synergistic in combination with VIC-1911 in human KRAS G12C-mutant NSCLC cell line xenograft models.
Additionally, in vivo studies demonstrated the synergy of VIC-1911 plus sotorasib compared with their respective monotherapies in KRAS G12C-mutant 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 G12C-mutant NSCLC that is naïve to 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. “Although 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. In addition, many patients who do respond rapidly develop acquired resistance and relapse within months. With this new dual-targeted approach combining AURKA and KRAS G12C inhibitors, we hope to improve therapeutic outcomes for our patients with KRAS G12C-mutant NSCLC.”
“VIC-1911 is a potent, 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.“
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