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LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma
LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma
CompletedPhase 2
Sponsor: Pfizer
Conditions: Melanoma
Interventions: LGX818, MEK162, LEE011, BGJ398, BKM120
Countries: United States, Australia, Canada, Germany, Italy, Netherlands, Spain, Switzerland
The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations.
Eligibility overview
Sex: ALL
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
Eligibility criteria
INCLUSION CRITERIA: * Age ≥ 18 years * Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer \[AJCC\]) * Documented evidence of BRAF V600 mutation. * Newly obtained tumor biopsy at baseline, and patient agrees to a mandatory biopsy at the time of progression, if not medically contraindicated. * Evidence of measurable disease, as determined by RECIST v1.1. INCLUSION CRITERIA for triple combinations: Progressive disease following prior treatment with LGX818/MEK162 combination. PRINCIPAL EXCLUSION CRITERIA Symptomatic or untreated leptomeningeal disease. * Symptomatic brain metastases. Patients previously treated or untreated for brain metastases that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for four weeks are allowed to enroll. Brain metastases must be stable at least 4 weeks with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs. * Patients who have developed brain metastases during Part I of the study may continue to Part II upon discussion with Novartis Medical Monitor. The brain metastasis must be either asymptomatic or treated and stable for at least 4 weeks and on a stable or tapering dose of steroids for at least 2 weeks. Patients with brain metastasis are not eligible for the combination with LEE011. * Known acute or chronic pancreatitis. * 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); * Clinically significant cardiac disease including any of the following: * CHF requiring treatment (NYH grade ≥ 2), * LVEF \< 50% as determined by MUGA scan or ECHO * History or presence of clinically significant ventricular arrhythmias or atrial fibrillation * Clinically significant resting bradycardia * Unstable angina pectoris ≤ 3 months prior to starting study drug * Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug, * QTcF \> 480 msec. Patients with any of the following laboratory values at Screening/baseline: * Absolute neutrophil count (ANC) \<1,500/mm3 \[1.5 x 109/L\] * Platelets \< 100,000/mm3 \[100 x 109/L\] * Hemoglobin \< 9.0 g/dL * Serum creatinine \>1.5 x ULN or calculated or directly measured CrCl \< 50% LLN (lower limit of normal) * Serum total bilirubin \>1.5 x ULN * AST/SGOT or ALT/SGPT \> 2.5 x ULN, or \> 5 x ULN if liver metastases are present Additional exclusion criteria for the triple combinations: LGX818/MEK162/BKM120: * Patients with fasting glucose \> 120 mg/dL or 6.7 mmol/L, and HbA1c \> 8 %. * Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist: * Patient has a score ≥ 12 on the PHQ-9 questionnaire * Patient has ≥ CTCAE grade 3 anxiety LGX818/MEK162/BGJ398: * History and/or current evidence of significant ectopic mineralization/ calcification with the exception of calcified lymph nodes and asymptomatic vascular calcification. * Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivits etc., confirmed by ophthalmologic examination LGX818/MEK162/LEE011: * Patients with uncontrolled hypertension (please refer to WHO-ISHguidelines) are excluded from study. * QTcF \>450 ms for males and \>470 ms for females Congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3 and magnesium levels below the clinically relevant lower limits at study entry * Current evidence of brain metastasis or brain metastasis detected by mandatory CT/MRI at screening * PT/INR or aPTT \> 1.5xULN Other protocol-defined inclusion/exclusion criteria may apply.
Locations (32)
- Los Angeles, California, United States
- Los Angeles, California, United States
- Los Angeles, California, United States
- Los Angeles, California, United States
- Los Angeles, California, United States
- Los Angeles, California, United States
- Los Angeles, California, United States
- New York, New York, United States
- New York, New York, United States
- New York, New York, United States
- Portland, Oregon, United States
- Portland, Oregon, United States
- Portland, Oregon, United States
- Portland, Oregon, United States
- Portland, Oregon, United States
- Nashville, Tennessee, United States
- Nashville, Tennessee, United States
- Melbourne, Victoria, Australia
- Melbourne, Victoria, Australia
- Toronto, Ontario, Canada
- Monteral, Quebec, Canada
- Heidelberg, Baden-Wurttemberg, Germany
- Würzburg, Bavaria, Germany
- Cologne, Germany
- München, Germany
- Würzburg, Germany
- Naples, Campania, Italy
- Naples, Italy
- Amsterdam, Netherlands
- Barcelona Cataluna, Barcelona, Spain
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