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