Background: Activity of direct covalent KRAS^G12C inhibitors in NSCLC is limited by mutational and adaptive resistance. AURKA has roles in centrosome maturation and cytokinesis. AURKA amplification/overexpression is reported in multiple tumors, including NSCLC, and AURKA signaling may mediate adaptive resistance to KRAS inhibition. VIC-1911 is a highly selective, orally active small molecule inhibitor of AURKA. VIC-1911 demonstrated monotherapy activity in vitro in KRAS^G12C-mutant human NSCLC cells with intrinsic and acquired resistance to the KRAS^G12C inhibitor sotorasib, and combination VIC-1911 and sotorasib showed synergy in the same cell lines. Combination VIC-1911 and sotorasib delayed the emergence of adaptive resistance in vitro. These findings suggest that 1) AURKA activation is present in both intrinsic and acquired resistance to sotorasib in KRAS^G12C-mutant NSCLC and 2) the combination of VIC-1911 and sotorasib is a potential therapeutic approach for KRAS^G12C-mutant NSCLC with intrinsic or acquired resistance to sotorasib monotherapy. In addition, in vivo data suggest both sotorasib and adagrasib are synergistic in combination with VIC-1911 in human KRAS^G12C-mutant NSCLC cell line xenograft models. Methods: A non-randomized, open-label Phase 1a/1b study of VIC-1911, an aurora kinase A inhibitor, administered as monotherapy and in combination with sotorasib for the treatment of advanced KRAS^G12C-mutant NSCLC is in progress. Participants ≥18 years, with locally advanced or metastatic KRAS^G12C-mutant NSCLC, prior treatment with at least 1 line of PD-1/PD-L1 inhibitor therapy with or without platinum-based chemotherapy and have adequate organ function are eligible. Both KRAS^G12C inhibitor naïve and experienced patients are eligible. VIC-1911 monotherapy is given at oral doses of 25 – 90 mg twice daily in dose escalation and at the VIC-1911 maximum tolerated dose (MTD) in the expansion cohort in patients who are refractory/relapsed on prior KRAS^G12C inhibitor therapy. The combination regimen includes dose escalation with VIC-1911 at oral doses of 75, 150 or 200 mg twice daily on days 1-4, 8-11 and 15-18 every 28-day cycle plus sotorasib 960 mg daily in patients who are refractory/relapsed or naïve to prior KRAS^G12C inhibitor therapy. In dose escalation, a 3+3 schema is followed with dose limiting toxicity (DLT) criteria for toxicity and a sample size ≤ 36. For expansion cohorts, the sample size is based on Simon 2-stage optimal design, with a sample size ≤ 104. VIC-1911 and sotorasib dose modification criteria are provided. Supportive medications are allowed and early stopping rules for toxicity will be followed. VIC-1911 pharmacokinetics will be assessed. Pharmacodynamics will be determined from ctDNA and tumor biomarker analysis. Clinical trial information: NCT05374538.