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

A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.

To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.

In response to developments in the treatment of melanoma, the sponsor reviewed the data from the ongoing study and decided to halt further enrollment of patients in the Phase Ib part of the study. Consequently, the Phase II part of the study was not performed. Early termination of the study was not due to any safety concerns.

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.