- Patients must be diagnosed with ALK-positive advanced NSCLC. The tumor must be
ALK-positive as determined by ALK rearrangement in 15% of cells (as measured by FISH
using the Vysis break-apart ALK probe) or by using the Ventana ALK IHC test. The
analysis may be performed locally.
- Eastern cooperative oncology group (ECOG) performance status 2.
- Measurable disease as per RECIST v1.1
- Availability of tumor sample:
For ALK inhibitor nave patients:
o A representative tumor sample must be submitted. An archival tumor specimen is
For patients after progression on an ALK inhibitor:
o A new tumor biopsy is required unless a biopsy performed after progression on the
patient's most recent ALK inhibitor is available for submission For all patients a newly
obtained tumor specimen must be submitted if no appropriate archival sample is available.
In the event that no sample is available and a new biopsy cannot be obtained, enrollment
may be considered after discussion with the sponsor.
- For Phase II part:
- Group A: prior therapy with any ALK inhibitor is not permitted.
- Group B: progression following any ALK inhibitor(s) other than ceritinib is
required and the last dose of the ALK inhibitor must be no more than 60 days
prior to the first dose of study drug. Prior ceritinib is not permitted.
- Group C: progression following ceritinib is required and the last dose of
ceritinib must be no more than 60 days prior to the first dose of study drug.
- Patients who have previously received ceritinib must have tolerated a dose of
ceritinib 600 mg QD, or greater.
- Patients with symptomatic central nervous system (CNS) metastases who are
neurologically unstable or require increasing doses of steroids or local CNS-directed
therapy to control their CNS disease
- Impaired cardiac function or any clinically significant cardiac disease
- Patients with abnormal laboratory values during screening and on day 1 of pre-dose
- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of ceritinib or LEE011
- Patients who are currently receiving treatment (that cannot be discontinued at least
1 week prior to the initiation of the study) with agents that are known to be any of
the following: strong inducers or inhibitors of CYP3A4/5; sensitive substrates of
CYP3A; substrates of CYP3A4/5 or CYP2C9 with a narrow therapeutic index.
- Patient has a history of pancreatitis or history of increased amylase or lipase that
was due to pancreatic disease.
Other protocol-defined inclusion/exclusion criteria may apply.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Overall Response Rate (ORR) - Phase Ib & II
Frequency of adverse events/serious adverse events
PK parameters of LEE011 and ceritinib
Frequency of dose interruptions and dose reductions (phase lb & ll)
Progression free survival (PFS) per RECIST v1.1 - Phase Ib & II
Duration of response (DOR)
Time to response (TTR) - Phase Ib & II
Disease Control Rate (DCR) - Phase Ib & II
Overall survival (OS) - Phase Ib & II
Severity of adverse events/serious adverse events