Phase Ib/II Study of Efficacy and Safety of MEK162 and Panitumumab, in Adult mCRC Patients With Mutant or Wild-type RAS Tumors

A Phase Ib/II, Open-label, Multi-center, Dose Escalation Study of MEK162 in Combination With Panitumumab in Adult Patients With Mutant RAS or Wild-type RAS Metastatic Colorectal Cancer

The primary purpose of the phase Ib is to estimate the MTD/RPD2 and of the phase II is to assess the anti-tumor activity of MEK162 in combination with panitumumab.

Inclusion Criteria:

• Age ≥ 18 years
• Metastatic colorectal cancer
• Progression on or following standard therapy, or no standard therapy (phase Ib). Progression on or following at least 2-prior fluoropyrimidine-containing chemotherapy regimens (phase II)
• Written documentation of mutant or wild-type RAS
• Life expectancy ≥ 3 months
• ECOG performance status ≤ 2

Exclusion Criteria:

Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors

• Previous treatment with MEK-inhibitors
• History of severe infusion reactions to monoclonal antibodies.
• Symptomatic or untreated leptomeningeal disease
• Symptomatic brain metastasis
• Current evidence of retinal disease; history of CSR, RVO or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO and history of keratitis.
• Acute or chronic pancreatitis
• Clinically significant cardiac disease
• Not adequate hematologic, renal and hepatic function