A Phase I, Open-Label, Dose Escalation Study of Oral LGK974 in Patients with Malignancies Dependent on Wnt Ligands

The primary purpose of this study is to find the recommended dose of LGK974 as a single agent
and in combination with PDR001 that can be safely given to adult patients with selected solid
malignancies that have progressed despite standard therapy or for which no effective standard
therapy exists

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:

- cutaneous melanoma that was primary refractory to prior anti-PD-1 therapy, defined as
a best response of progressive disease or stable disease for <= 4 months, or disease
recurrence with the first 6 months of adjuvant therapy. Patients with BRAF V600-mutant
melanoma must have also received and been failed by prior systemic therapy with BRAF
V600 inhibitor, with or without a MEK inhibitor.

- Cutaneous melanoma with acquired resistance to prior anti-PD-1 therapy, defined as
progressive disease following response (PR or CR) or following stable disease for > 4
months. Patients with BRAF V600-mutant melanoma must have also received and been
failed by prior systemic therapy with a BRAF V600 inhibitor, with or without a MEK
inhibitor.

Exclusion Criteria:

- Impaired cardiac function

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of 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, 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