A Dose Escalation/Expansion Study of LDK378 in Patients With Tumors Characterized by Genetic Abnormalities in Anaplastic Lymphoma Kinase

Inclusion Criteria:

- ECOG Performance Status of ≤ 2 and life expectancy of ≥ 12 weeks.

- Diagnosed with a locally advanced or metastatic malignancy that has progressed despite
standard therapy, or for which no effective standard therapy exists. Only patients
with tumors characterized by genetic abnormalities in ALK were enrolled.

- For NSCLC, an ALK translocation must be detected by FISH in ≥ 15% of tumor cells.

- In patients with diseases other than NSCLC, ALK translocation is not required and
overexpression of ALK protein may be considered indicative of a genetic abnormality in
ALK.

- Patients with measurable or non-measurable disease as determined by modified RECIST
version 1.0 in dose-escalation phase, and patients with at least one measurable lesion
as determined by RECIST 1.0 in expansion phase.

Exclusion Criteria:

- Patients with symptomatic central nervous system (CNS) metastases who were
neurologically unstable or required increasing doses of steroids to control their CNS
disease were excluded.

- Patients with a prior or current history of a second malignancy, impaired GI function,
history of pancreatitis or increased amylase or lipase, known diagnosis of HIV, and
clinically significant cardiac disease were excluded.

- Patients treated with chemotherapy or biologic therapy or other investigational agent
< 2 weeks prior to starting study drug for compounds with a half-life ≤ 3 days, and <
4 weeks prior to starting study drug for compounds with a prolonged half-life were
excluded.

- Further, patients treated with medications that were known to be strong inhibitors or
inducers of CYP3A4/5 that could not be discontinued at least a week prior to start of
treatment with LDK378 and for the duration of the study were also excluded.

Other protocol-defined inclusion/exclusion criteria may apply