Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02292550
• Date of registration: 12/11/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: Study of Safety and Efficacy of LEE011 and Ceritinib in Patients With ALK-positive Non-small Cell Lung Cancer.
• Scientific title: A Phase Ib/II Study of the ALK Inhibitor Ceritinib in Combination With the CDK4/6 Inhibitor LEE011 in Patients With ALK-positive Non-Small Cell Lung Cancer
• Date of first enrolment: May 14, 2015
• Target sample size: 27
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02292550
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

France, Italy, Korea, Republic of, Spain, Taiwan, United States

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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 naïve patients:

o A representative tumor sample must be submitted. An archival tumor specimen is acceptable

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.

Exclusion Criteria:

- For Phase I part:

o Patients who have not previously received at least one line of therapy for
ALK-positive NSCLC

- 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 been unable to tolerate ceritinib, in the opinion of the
investigator. Exceptions to this exclusion include nausea, vomiting and diarrhea in
patients taking ceritinib under fasted conditions.

- 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

- 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.

- Patient with impaired cardiac function or any clinically significant uncontrolled
cardiac disease, and/or, cardiac repolarization abnormality, including any of the
following:

Clinically significant heart disease such as CHF requiring treatment (NYH grade = 2),
history of angina pectoris, myocardial infarction, symptomatic pericarditis, or coronary
artery bypass graft (CABG) within 6 months prior to study entry, documented cardiomyopathy,
or left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition scan (MUGA) or echocardiogram (ECHO).

Uncontrolled systolic blood pressure (SBP) =160 mmHg and/or diastolic blood pressure (DBP)
=100 mmHg, with or without anti-hypertensive medication. Initiation or adjustment of
antihypertensive medication (s) is allowed prior to screening, Systolic blood pressure
(SBP) <90 mmHg Standard 12-lead ECG values defined as the mean of the triplicate ECGs and
assessed by central laboratory

- QTcF interval at screening >450 msec (using Fridericia's correction)

- Resting heart rate <50 bpm or > 90 bpm

Long QT syndrome or family history of idiopathic sudden death or congenital long QT
syndrome, or any of the following:

- Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or
hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia

- Concomitant medication(s) with a known risk to prolong the QT interval and/or known to
cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative
medication (e.g. within 5 half-lives or 7 days prior to starting study drug)

- Inability to determine the QTcF interval Clinically significant cardiac arrhythmias
(e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV
block (e.g., bifascicular block, Mobitz type II and third degree AV block).

Other protocol-defined inclusion/exclusion criteria may apply.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-small Cell Lung Cancer

Intervention(s)

Drug: Ribociclib

Drug: Ceritinib

Primary Outcome(s)

Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase Ib ) [Time Frame: 1 month]

Overall Response Rate (ORR) as per RECIST v1.1 [Time Frame: Up to 24 months]

Exposure to LEE011 and ceritinib (Phase Ib ) [Time Frame: Up to 6 months]

Secondary Outcome(s)

Time to response (TTR) - Phase Ib & II [Time Frame: Up to 24 months]

Disease Control Rate (DCR) - Phase Ib & II [Time Frame: Up to 24 months]

Progression free survival (PFS) per RECIST v1.1 - Phase Ib & II [Time Frame: Up to 24 months]

Duration of response (DOR) [Time Frame: Up to 24 months]

Frequency of adverse events/serious adverse events [Time Frame: Up to 24 months]

Overall survival (OS) - Phase Ib & II [Time Frame: Up to 24 months]

Frequency of dose interruptions and dose reductions (phase lb & ll) [Time Frame: Up to 24 months]

PK parameters of LEE011 and ceritinib [Time Frame: Up to 6 months]

Overall Response Rate (ORR) - Phase Ib & II [Time Frame: Up to 24 months]

Severity of adverse events/serious adverse events [Time Frame: Up to 24 months]

Secondary ID(s)

CLEE011X2110C

Source(s) of Monetary Support

Please refer to primary and secondary sponsors