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

Inclusion Criteria

• 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 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/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 Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes: - ≤ 4 weeks for radiation therapy or ≤ 2 weeks for limited field radiation for palliation prior to the first dose of study treatment. - ≤ 4 weeks or ≤ 5 half-life (whichever is shorter) for small molecule therapeutics. - ≤ 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors. Participants participating in additional parallel investigational drug or medical device studies. All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are neurologically unstable 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). Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures. Other protocol-defined exclusion criteria may apply

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Novartis Pharmaceuticals Corporation

• Primary ID CLXH254C12201
• Secondary IDs NCI-2020-07512
• Clinicaltrials.gov ID NCT04417621