This is a phase I/II multi-center open-label proof of concept study, consisting of two parts. Part A of this study is designed to identify the recommended phase 2 dose (RP2D) of the combination regimen of dacomitinib plus PD-0325901 in patients with advanced KRAS mutant (KRASm) non-small cell lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the combination of dacomitinib and PD-0325901 versus standard of care therapy in patients with advanced KRASm NSCLC. It is hypothesized that with this combination strategy the progression free survival of patients with KRASm NSCLC will be doubled.

Inclusion Criteria:

• Histological or cytological proof of advanced non-small cell lung cancer
• Written documentation of KRAS (exon 2, 3 or 4) mutation
• At least 18 years of age or older
• Able and willing to give written informed consent
• WHO performance status of 0 or 1

Exclusion Criteria:

• Symptomatic or untreated leptomeningeal disease
• Symptomatic brain metastasis
• Impairment of gastrointestinal function
• Uncontrolled infectious disease
• Left ventricular ejection fraction < 50%
• Retinal degenerative disease or with history of uveitis, retinal vein occlusion or retinal detachment

Other protocol-defined inclusion/exclusion criteria may apply