Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.
Locally Advanced Metastatic BRAF Mutant Melanoma

About this trial
This is an interventional treatment trial for Locally Advanced Metastatic BRAF Mutant Melanoma focused on measuring Open-label dose escalation, BRAF inhibitor, LEE011, CDK4/6, LGX818, RAF kinase inhibitor, Metastatic melanoma, BRAF, V600
Eligibility Criteria
Inclusion Criteria:
- Age ≥18 years.
- Diagnosis of locally advanced or metastatic melanoma along with written documentation of BRAF V600 mutation.
- ECOG performance status of 0 - 2.
- Patients enrolled into Phase Ib must have evidence of evaluable and/or measurable disease as determined by RECIST v1.1.
- Patients enrolled into Phase II (BRAFi naïve and resistant) must have evidence of measurable disease as determined by RECIST v1.1.
- Archival tumor tissue must be obtained for patients enrolled in Phase Ib and Phase II arm 1a/b- BRAFi naïve patients. If an archival tumor tissue is not available, a fresh tumor sample is acceptable.
- For patients enrolled in the phase II arm 2, patients must agree to undergo a fresh tumor biopsy unless one was collected prior to study entry but at the time of disease relapse from the most recent BRAFi treatment.
Exclusion Criteria:
- Symptomatic brain metastases.
- Symptomatic or untreated leptomeningeal disease.
- Patients with inadequate laboratory values during screening.
- In the phase II BRAFi naïve arms (1a/b), prior exposure to CDK4/6 inhibitor (e.g., PD 0332991)
- Impaired cardiac function or clinically significant cardiac diseases.
- Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 or LGX818.
- Patients with concurrent severe and/or uncontrolled concurrent medical conditions.
- Previous or concurrent malignancy.
- Major surgery < 2 weeks before starting study treatment
- Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C.
Other protocol-defined inclusion/exclusion criteria may apply.
Sites / Locations
- University of Colorado Dept of Oncology
- Karmanos Cancer Institute Dept of Oncology
- Memorial Sloan Kettering Cancer Center Dept Oncology
- Oregon Health & Science University Dept. of OHSU (3)
- Vanderbilt University Medical Center SC - Dept of Oncology .
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Phase Ib
Phase II arm 1a
Phase II arm 1b
Phase II arm 2
Phase Ib will randomize 18 patients with BRAF mutant melanoma, who are naïve or who have progressed on prior therapy to evaluate the safety and tolerability of the combination of LEE011 and LGX818.
Phase II arm 1a will randomize 60 patients that are naïve to prior BRAF inhibitor therapy to LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.
Phase II arm 1b will randomize 30 patients to LGX818. Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials. This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.
Phase II arm 2 will evaluate a single arm LEE011+LGX818 in 40 patients resistant to prior BRAF inhibitor therapy. Single agent LGX818 has shown limited activity in patients with melanoma who have failed prior BRAF inhibitor treatment; the contribution of LEE011 in this combination will be evaluated.