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 one week [Day -7 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 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