Inclusion Criteria:

• Male or female must be ≥ 12 years.
• For adolescent participants only (12-17 years): body weight > 40kg.
• Histologically confirmed unresectable or metastatic cutaneous melanoma.
• Documentation of BRAFV600 or NRAS mutation in tumor tissue prior to study treatment as determined by local assay agreed by Novartis or as determined by central pre-screening assessment performed at a Novartis designated laboratory.
• Previously treated for unresectable or metastatic melanoma.
• Participants with NRAS mutation:
  • Participants must have received prior systemic therapy for unresectable or metastatic melanoma with an anti-PD-1/PD-L1 checkpoint inhibitor as a single agent or in combination with anti-CTLA-4. No additional systemic treatment is allowed for unresectable or metastatic melanoma.
  • A maximum of two prior lines of systemic immunotherapy for unresectable or metastatic melanoma are allowed.
  • The last dose of prior therapy (anti-PD-1, anti-PD-L1 or anti-CTLA-4 must have been received more than four weeks before randomization.
  • Participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. The last progression must have occurred within 12 weeks prior to randomization in the study.
• Participants with BRAFV600 mutant disease:
  • Participants must have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1 or an PD-L1 as a single agent or in combination with anti-CTLA-4. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi as the last prior therapy. No additional systemic treatment is allowed for advanced or metastatic melanoma.
• A maximum of three prior lines of systemic therapy for unresectable or metastatic melanoma are allowed.
• The last dose of targeted therapy (last prior therapy) must have been received more than 2 weeks prior to randomization.
• Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy. The last progression must have occurred within 12 weeks prior to randomization in the study.
• Participants must have a site of disease amenable to repeated biopsies and must be willing to undergo a new tumor biopsy at baseline and during treatment according to the treating institution’s own guidelines and requirements for such procedure. Bone metastases are not acceptable as a site for biopsy.

Exclusion Criteria:

• All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are neurologically unstable.
• Insufficient bone marrow, hepatic or renal function at the screening visit.
• Abnormal ECG as determined by the mean of a triplicate ECG and assessed locally.
• Cardiac disease or cardiac repolarization abnormality.
• Presence of ≥ CTCAE grade 2 toxicity (except alopecia and ototoxicity, which are excluded if ≥ CTCAE grade 3) due to prior anti-cancer therapy.
• 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).