- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of
0 - 1.
- Patients enrolled into phase Ib may be enrolled with evaluable disease only. Patients
enrolled into the phase II expansion must have at least one measurable lesion as
defined by RECIST 1.1 criteria for solid tumors.
- Patients must have adequate organ function, as defined by the following parameter
1. Absolute Neutrophil Count (ANC) 1.5 x 109/L.
2. Hemoglobin (Hgb) 9 g/dL.
3. Platelets 75 x 109/L without transfusions within 21 days before 1st treatment.
4. PT/INR and aPTT 1.5 ULN.
5. Serum creatinine 1.5 ULN.
6. Serum total bilirubin 1.5 x upper limit of normal (ULN).
7. AST and ALT 3 x ULN, except in patients with tumor involvement of the liver
who must have AST and ALT 5 x ULN.
- Presence of any brain metastases detected by MRI or CT with i.v. contrast of the
brain at screening.
- Uncontrolled arterial hypertension despite medical treatment
- Impaired cardiac function or clinically significant cardiac diseases, including any
of the following:
1. Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition scan (MUGA) or echocardiogram (ECHO).
2. Congenital long QT syndrome or family history of unexpected sudden cardiac
3. QTcF corrected with Frederica's or Bazett's formula QTcB >450 ms for males and
>470 ms for females on screening ECG.
4. Angina pectoris 3 months prior to starting study drug
5. Acute myocardial infarction 3 months prior to starting study drug
6. Clinically significant resting bradycardia
7. History or presence of ventricular tachyarrhythmia
8. Unstable atrial fibrillation (ventricular response >100 bpm)
9. Complete left bundle branch block
10. Right bundle branch block and left anterior hemi block (bifascicular block)
11. Obligate use of a cardiac pacemaker or implantable cardioverter defibrillator
12. Any other clinically significant heart disease
- Patients who are currently receiving treatment with agents that are known to cause
QTc prolongation in humans.
- Patients who have neuromuscular disorders that are associated with elevated CK (e.g.,
inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal
muscular atrophy) or elevated baseline CK levels ( Grade 2)
- Patients who are currently receiving treatment with agents that are metabolized
predominantly through CYP3A4 and that have a narrow therapeutic window.
- Patients with concurrent severe and/or uncontrolled concurrent medical conditions
that could compromise participation in the study (i.e. uncontrolled diabetes
mellitus, clinically significant pulmonary disease, clinically significant
neurological disorder, active or uncontrolled infection).
- History or current evidence of retinal vein occlusion (RVO) or current risk factors
for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity
or hypercoagulability syndromes).
Other protocol related inclusion/exclusion criteria may apply.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Plasma concentration-time profile (AUCtau) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (AUCtau,ss) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (Cmin,ss) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profiles of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (Cmax) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (Cmax,ss) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (Tmax) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (Tmax,ss) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (accumulation ration, Racc) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (T1/2, acc) of LEE011 and MEK162 (phase Ib)
Plasma concentration-time profile (CL/F) of LEE011 and MEK162 (phase Ib)
Incidence of adverse drug reactions
Duration of Response (DoR) - Phase ll
Time to Progression (TTP) - Phase ll
Progression Free Survival (PFS) - Phase ll
Overall Survival (OS) - Phase ll
Best Overall Response (BOR) - Phase ll