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

Status:	Completed
Conditions:	Colorectal Cancer, Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	10/11/2017
Start Date:	December 2014
End Date:	June 23, 2017

A Phase Ib/II Multi-center, Open Label, Dose Escalation Study of WNT974, LGX818 and Cetuximab in Patients With BRAFV600-mutant KRAS Wild-type Metastatic Colorectal Cancer Harboring Wnt Pathway Mutations

The purpose of this study is to assess the safety and anti-tumor activity of the triple
combination of WNT974, LGX818 and cetuximab in BRAFV600-mutant mCRC with RNF43 mutations or
RSPO fusions.

The design of this study is based upon the translational and pre-clinical data that suggest
that Wnt pathway signals, increased due to RNF43 mutations or RSPO fusions, cooperate with
the EGFR and BRAF signals to maintain the growth of BRAFV600 CRCs. Inhibition of these
signals with the triple combination of WNT974, LGX818 and cetuximab may result in anti-tumor
activity.

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

We found this trial at

sites

Medical University of South Carolina Oncology Dept

Charleston, South Carolina 29425

Principal Investigator: Carolyn Britten

Phone: 843-792-9007

from

Charleston, SC