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

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Brief Title

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

Official 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

Brief Summary

      This was 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.

      The purpose of the study was to determine the MTD/RP2D of the LEE011 and ceritinib
      combination and evaluate whether the combination was safe and had beneficial effects in
      ALK-positive advanced non-small cell lung cancer patients.

      This trial did not progress to Phase II. Trial population terminated before reaching Phase II

Detailed Description

      In Sep-2016, Novartis made a decision not to move into phase ll after the primary objective
      for this study was met. Because the study never made it to phase ll, the study phase has been
      changed from a phase l/ll to a phase l.

Study Phase

Phase 1

Study Type


Primary Outcome

Incidence rate of dose limiting toxicities (DLTs) during the first cycle of treatment (Phase Ib )

Secondary Outcome

 Overall Response Rate (ORR) - Phase Ib & II


Non-small Cell Lung Cancer



Study Arms / Comparison Groups

 Ribociclib 100 mg + Ceritinib 300 mg
Description:  LEE011 capsule for oral use (ribociclib) and Ceritinib for oral use


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

May 14, 2015

Completion Date

September 26, 2018

Primary Completion Date

September 26, 2018

Eligibility 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

        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.




18 Years - N/A

Accepts Healthy Volunteers



Novartis Pharmaceuticals, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party


Study Sponsor

Novartis Pharmaceuticals

Study Sponsor

Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals

Verification Date

July 2019