Conditions: Locally Advanced Metastatic BRAF Mutant Melanoma
Keywords: Open-label dose escalation BRAF inhibitor LEE011 CDK4/6 LGX818 RAF kinase inhibitor Metastatic melanoma BRAF V600
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 28
Healthy volunteers: no

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

Detailed description:
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.

Arms:
arm 1: 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. arm 2: 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. arm 3: 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. arm 4: 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.

Interventions: intervention 1: LEE011 intervention 2: LGX818
Intervention descriptions: intervention 1: LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle). intervention 2: LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).

Protocol document: