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