Phase I Study of LDK378 in Pediatric, Malignancies With a Genetic Alteration in Anaplastic Lymphoma Kinase (ALK)

LDK378 is a novel inhibitor of ALK that is active in a broad range of ALK-activated tumor
models, including models driven by mutated versions of ALK known to be resistant to
crizotinib, and by ALK gene amplification.

The primary purpose of this study is to determine the maximum tolerated dose and/or
recommended dose for expansion in pediatric patients, and to delineate a clinical dose to be
used in any future pediatric studies, with and without food. This study will also assess the
safety, tolerability, PK and preliminary evidence of antitumor activity of LDK378 in
pediatric patients with neuroblastoma, and other ALK-activated tumors.

Inclusion Criteria:

- Diagnosed with a locally advanced or metastatic malignancy that has progressed despite
standard therapy, or for which no effective standard therapy exists

- Age ≥ 12 months and < 18 years

- The tumor must carry a genetic alteration of ALK

- Patients must have evaluable or measurable disease

Exclusion criteria:

- Symptomatic central nervous system (CNS) metastases who are neurologically unstable or
require increasing doses of steroids or local CNS-directed therapy (such as
radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease

- Clinically significant, uncontrolled heart disease

- Inadequate end organ function as defined by specified laboratory values

- Use of medications that are known to be strong inhibitors or inducers of CYP3A4/5 that
cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for
the duration of the study

- Use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be
discontinued at least 1 week prior to start of treatment with LDK378 and for the
duration of the study.

- History of interstitial lung disease or interstitial pneumonitis, including clinically
significant radiation pneumonitis

- History of pancreatitis or history of increased amylase or lipase that was due to
pancreatic disease.

- Medications with a known risk of prolongation of QT interval

Other protocol defined inclusion and exclusion criteria may apply