RO5126766 for Patients With Advanced KRAS-Mutant Lung Cancer

Inclusion Criteria: * Histologically or cytologically proven diagnosis of advanced NSCLC * Documented presence of KRAS mutation * Prior treatment with a PD-1/L1 inhibitor. Patients who were deemed not eligible for therapy with a PD-1/L1 inhibitor by their treating physician will also be eligible in the dose expansion phase. * Prior treatment with chemotherapy * Able to take oral medications * Measurable and/or evaluable disease (RECIST 1.1) indicator lesion not previously irradiated * Karnofsky performance status (KPS) ≥ 70% (ECOG of 0 or 1 also acceptable) * Age≥ 18 years old * Hematological and biochemical indices within the ranges shown below Hematological and biochemical indices within the ranges shown below (These measurements must be performed within two weeks \[Day 14 to Day 1\] before the patient is entered into the trial). * AST, ALT ≤ 2.5 x ULN - Total bilirubin ≤ 1.5 x ULN -Albumin≥2.5g/dL * Creatinine \< 1.5 x ULN OR calculated creatinine clearance ≥50mL/min * Absolute neutrophil count (ANC) ≥ 1,200 cells/mm3 * Hemoglobin ≥9.0 g/dL * Platelets ≥100,000/mm\^3. * A negative serum pregnancy test obtained within two weeks prior to the administration of the study drug in all women of child bearing potential Exclusion Criteria: * Patients with symptomatic brain metastasis requiring escalating doses of steroids * Patients with grade 2 or greater diarrhea prior to study initiation despite maximal medical management * History of any bowel disease including abdominal fistula, gastro-intestinal perforation * History of acute pancreatitis within 1 year of study entry or history of chronic pancreatitis * History of or ongoing alcohol abuse that, in the opinion of the treating physician, would compromise compliance or impart excess risks associated with study participation. * Pregnant or lactating women * Any type of systemic therapy (chemotherapy or experimental drugs) within 3 weeks of starting treatment on protocol (within 6 weeks for for nitrosoureas and mitomycin C) * Radiotherapy within 2 weeks of starting treatment on protocol * Prior treatment with MEK, RAF, or ERK inhibitor(s) * Significant uncontrolled or active cardiovascular disease, specifically including, but not restricted to: * History of clinically significant (as determined by the treating physician) atrial arrhythmia * Any ventricular arrhythmia * History of congenital long QT syndrome. * Abnormal QTc (≥ 450 msec in males and ≥ 470 msec in females) * Ejection fraction ≤ 50% as assessed by echocardiogram * Concurrent congestive heart failure * Prior history of class III/ IV heart failure (New York Heart Association \[NYHA\] * Myocardial infarction within the last 6 months * Unstable angina or severe obstructive pulmonary disease * Patients with baseline risk factors for central serous retinopathy or retinal vein occlusion such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure \>21 mmHg Uncontrolled hypertension (Diastolic blood pressure \> 100 mmHg; Systolic blood pressure \> 150 mmHg). * History of central serous retinopathy or retinal vein occlusion * History of prior malignancy within 2 years that requires/ed treatment. Patients who are considered NED from a malignancy may be considered on a case by case basis. * Known active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infections * Patients exposed to CYP3A4 inhibitors within 7 days prior to the first dose and CYP3A4 inducers 7 days prior to the first dose. RO5126766 (CH5126766) is metabolised mainly by CYP3A4 therefore concomitant administration of strong inhibitors and inducers of cytochrome p450 3A4 enzymes is forbidden during study treatment (for a complete list please see Appendix A). * Any other condition that, in the opinion of the investigator, may compromise the safety, compliance of the patient, or would preclude the patient from successful completion of the study