Selected subjects will include males and females age ≥18 years; histologically confirmed locally advanced or metastatic KRAS G12C-mutated NSCLC; received at least 1 prior line of cancer therapy with a PD-1 or PD-L1 inhibitor with or without platinum-based chemotherapy; recovered from all acute toxicities (≤ Grade 1) due to prior therapy; adequate renal and hepatic function; and no known history of significant cardiac, hepatic or ocular disease.~Dose Escalation Phase:~Following screening, a total of up to 36 subjects are anticipated to establish the dose limiting toxicity (DLT) and maximum tolerated doses (MTDs) of VIC-1911 monotherapy and VIC-1911 in combination with sotorasib therapy.~Cohort 1a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 monotherapy. Up to 24 subjects are anticipated in this cohort.~Cohort 1b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy or are naïve to KRASG12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. Up to 12 subjects are anticipated in this cohort.~A 3+3 dose escalation schema will be followed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of VIC-1911 and VIC-1911 plus sotorasib combination. A total of at least 6 subjects will be treated at the MTD in each group before initiating the Expansion Phase.~Expansion Phase:~Following screening, a total of 104 subjects with KRAS G12C-mutated locally advanced or metastatic NSCLC are anticipated to expand the disease treatment settings of VIC-1911 as monotherapy or in combination with sotorasib. VIC-1911 monotherapy and VIC-1911 plus sotorasib combination therapy will be administered orally at the MTDs established during the Dose Escalation Phase.~Cohort 2a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 monotherapy. (n=29)~Cohort 2b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.(n=29)~Cohort 2c: Subjects who are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. (n=46)~VIC-1911 and sotorasib will be taken in the fasted state, 1 hour before or 2 hours after a meal.~Subjects who demonstrate clinical benefit (CR, PR or SD) will be allowed to continue therapy with VIC-1911 and sotorasib until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.~Disease response will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1).~Blood for hematology, coagulation parameters and serum chemistry determinations and urine will be collected, ECGs will be taken and ophthalmologic exams will be conducted during the study.~Blood will be taken for PK assessment of VIC-1911 and PD assessment of circulating tumor DNA biomarker determinations.~Tumor biopsies will be taken from consenting subjects at Screening and on-study for correlative biomarker determinations. Results will be correlated with clinical outcome.
This is a Phase 1a/1b study of aurora kinase A inhibitor VIC-1911 administered as monotherapy and in combination with sotorasib for the treatment of locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC).