A Study of LGK974 in Patients With Malignancies Dependent on Wnt Ligands

Inclusion Criteria:

Diagnosis of locally advanced or metastatic cancer that has progressed despite standard
therapy or for which no effective standard therapy exists and histological confirmation of
one of the following diseases indicated below:

Single Agent Dose escalation part:documented B-RAF mutant colorectal cancer or pancreatic
adenocarcinoma. In addition, tumors of any histological origin with documented genetic
alterations upstream in the Wnt signaling pathway are eligible with prior agreement with
Novartis.

Single Agent Dose expansion part: documented B-RAF mutant colorectal cancer with documented
RNF43 mutation and/or RSPO fusion or pancreatic adenocarcinoma with documented RNF43
mutation. In addition, patients with tumors of any histological origin with documented
genetic alterations upstream in the Wnt signaling pathway (e.g. RNF43 or RSPO fusion) are
eligible with prior agreement with Novartis

LGK974 with PDR001: Dose escalation: patients with the following cancers that were
previously treated with anti-PD-1 therapy and whose best response on that therapy was
progressive disease (i.e. primary refractory): melanoma, lung SCC, HNSCC. Patients with
esophageal SCC, cervical SCC or TNBC who are either naïve or primary refractory to prior
anti-PD-1 therapy.

LGK974 with PDR001: Dose expansion: patients with pancreatic cancer, or TNBC, or melanoma,
or head and neck cancer.

Exclusion Criteria:

- Impaired cardiac function

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of oral LGK974 (e.g., ulcerative diseases,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel
resection)

- Brain metastases that have not been adequately treated

- Malignant disease other than that being treated in this study

- Laboratory abnormalities as specified in the protocol

- Osteoporosis, severe or untreated osteopenia

- Bone fractures within the past year

- Pathologic bone fracture

- Active, known or suspected autoimmune disease or severe hypersensitivity reactions to
other monoclonal antibodies

Other protocol-defined inclusion/exclusion criteria may apply