Study of WNT974 in Combination With LGX818 and Cetuximab in Patients With BRAF-mutant Metastatic Colorectal Cancer (mCRC) and Wnt Pathway Mutations

Inclusion criteria

• Male or female aged ≥ 18 years
• Histological or cytological confirmed metastatic colorectal cancer
• Written documentation of KRAS wild-type status and BRAFV600-mutation with RNF43 mutation and/or RSPO fusion
• Progression of disease after at least one prior standard of care regimen or intolerant to irinotecan based regimens
• Availability of a representative tumor specimen (primary or metastatic, archival or newly obtained)
• Measurable disease as per RECIST v1.1
• Eastern cooperative oncology group (ECOG) performance status ≤ 2

Exclusion criteria

• Phase II only: Prior treatment with RAF inhibitors, Wnt pathway inhibitors, cetuximab, panitumumab, and/or other EGFR inhibitors
• Symptomatic brain metastasis. Patients previously treated or untreated for these conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic therapy are allowed to enroll
• Current treatment with medications or consuming foods that are strong inhibitors or inducers of CYP3A4/5 or herbal medications and that cannot be discontinued at least one week prior to the start of treatment.
• Symptomatic or untreated leptomeningeal disease
• Acute or chronic pancreatitis
• Clinically significant cardiac disease
• Patients with any of the following laboratory values at Screening/baseline

• Absolute neutrophil count (ANC) <1,500/mm3
• Platelets < 100,000/mm3
• Hemoglobin < 9.0 g/dL
• Serum creatinine >1.5 x ULN or calculated or directly measured CrCl < 50% lower limit of normal
• Serum total bilirubin >1.5 x ULN
• AST/SGOT and/or ALT/SGPT > 2.5 x ULN, (> 5 x ULN if liver metastases present)
• Patients with impaired hepatic function as defined by Childs-Pugh class B or C
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral WNT974/LGX818

Other protocol-defined inclusion/exclusion criteria may apply