A Randomized, Open-label, Multi-arm, Two-part, Phase II Study to Assess the Efficacy and Safety of Multiple LXH254 Combinations in Patients with Previously Treated Unresectable or Metastatic BRAFV600 or NRAS Mutant Melanoma
e primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma
1.The primary objective of this study is to evaluate the efficacy of each combination arm, as measured by confirmed objective response rate (ORR) by local investigator s assessment per RECIST v1.1 2.To characterize the safety and tolerability of each combination arm through the incidence and severity of AEs including changes in laboratory values, vital signs, cardiac assessment, dose interruptions, reduction and permanent discontinuations of study treatments. 3.To further evaluate the efficacy of each combination arm by duration of response (DOR), progression free survival (PFS) and disease control rate (DCR) using RECIST v1.1, per local assessment. Additionally, for the treatment combination arm(s) that expanded, DoR, PFS, DCR and ORR will be evaluated using RECIST v1.1 per central assessment. 4.To evaluate the overall survival (OS) of each combination arm To characterize the pharmacokinetics of each combination regimen through serum/plasma concentration and pharmacokinetic parameters of each combination regimen.
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.
Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
> > > 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
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