Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma

Inclusion Criteria

• •Male or female must be ≥ 12 years For adolescents only (12-17 years): body weight \> 40kg Histologically confirmed unresectable or metastatic cutaneous melanoma
• •Previously treated for unresectable or metastatic melanoma:
• •Participants with NRAS mutation:
• •Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents.
• •A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents administered with CPI are permitted.
• •To rule out pseudo-progression, participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. Confirmation is not required for patients who remained on treatment for \>6 months.
• •Participants with BRAFV600 mutant disease:
• •Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi (+/- CPI allowed) as the last prior therapy.
• •A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents with CPI are permitted.
• •A maximum of one line of targeted therapy is allowed, and it must be the most recent line of therapy.
• •Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy.