VITRAC Therapeutics, LLC (VITRAC) 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.“

About VITRAC Therapeutics, LLC:
VITRAC is an integrated oncology research and development company with experience developing, managing, and optimizing global pharmaceutical drug development programs from late discovery, translational research, and clinical development through market authorization and post-marketing life-cycle management.

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