Clinical Trials /

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

NCT04417621

Description:

The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma

Related Conditions:
  • Cutaneous Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
  • Official Title: A Randomized, Open-label, Multi-arm, Two-part, Phase II Study to Assess Efficacy and Safety of Multiple LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic BRAFV600 or NRAS Mutant Melanoma

Clinical Trial IDs

  • ORG STUDY ID: CLXH254C12201
  • NCT ID: NCT04417621

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
LXH254LXH254 + LTT462
LTT462LXH254 + LTT462
TrametinibLXH254 + trametinib
RibociclibLXH254 + ribociclib

Purpose

The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma

Trial Arms

NameTypeDescriptionInterventions
LXH254 + LTT462Experimental
  • LXH254
  • LTT462
LXH254 + trametinibExperimental
  • Trametinib
LXH254 + ribociclibExperimental
  • Ribociclib

Eligibility 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
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate
Time Frame:35 months
Safety Issue:
Description:Confirmed ORR using RECIST v1.1, per local assessment

Secondary Outcome Measures

Measure:Duration of Reposnse (DOR)
Time Frame:4 years
Safety Issue:
Description:Local and central assessment
Measure:Progression Free Survival (PFS)
Time Frame:4 years
Safety Issue:
Description:
Measure:Disease Control Rate (DCR)
Time Frame:3 years
Safety Issue:
Description:Using RECIST v1.1, per local and central assessment
Measure:Overall Survival (OS)
Time Frame:4 years
Safety Issue:
Description:
Measure:Derived PK parameter (Cmax) for LXH254 & LTT462
Time Frame:Up to 5 months
Safety Issue:
Description:
Measure:Derived PK parameter (Cmax) for LXH254 & trametinib
Time Frame:Up to 5 months
Safety Issue:
Description:
Measure:Derived PK parameter (Cmax) for LXH254 & ribociclib
Time Frame:Up to 5 months
Safety Issue:
Description:
Measure:Derived PK parameter (AUC) for LXH254 & LTT462
Time Frame:Up to 5 months
Safety Issue:
Description:
Measure:Derived PK parameter (AUC) for LXH254 & trametinib
Time Frame:Up to 5 months
Safety Issue:
Description:
Measure:Derived PK parameter (AUC) for LXH254 & ribociclib
Time Frame:Up to 5 months
Safety Issue:
Description:
Measure:Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:35 months
Safety Issue:
Description:Number of participants with Adverse Events (AEs) and SAEs as a measure of safety and tolerability
Measure:Dose Interruptions
Time Frame:35 months
Safety Issue:
Description:Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Measure:Dose reductions
Time Frame:35 months
Safety Issue:
Description:Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • LXH254
  • Melanoma
  • NRAS
  • BRAF
  • LTT462
  • Trametinib
  • Ribocliclib

Last Updated

September 8, 2020