Clinical Trials /

Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations

NCT02607813

Description:

A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations
  • Official Title: A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations

Clinical Trial IDs

  • ORG STUDY ID: CLXH254X2101
  • SECONDARY ID: 2015-003421-33
  • NCT ID: NCT02607813

Conditions

  • NSCLC
  • Ovarian Cancer
  • Melanoma
  • Other Solid Tumors

Interventions

DrugSynonymsArms
LXH254Dose escalation LXH254
PDR001Dose expansion: LXH254 + PDR001

Purpose

A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.

Trial Arms

NameTypeDescriptionInterventions
Dose escalation LXH254Experimental
  • LXH254
Dose expansion LXH254: Group 1Experimental
  • LXH254
Dose expansion LXH254: Group 2Experimental
  • LXH254
Dose expansion LXH254: Group 3Experimental
  • LXH254
Dose expansion: LXH254 + PDR001Experimental
  • LXH254
  • PDR001
Dose escalation LXH254 + PDR001Experimental
  • LXH254
  • PDR001

Eligibility Criteria

        Inclusion Criteria:

          -  All patients participating in this clinical trial must have progressed following
             standard therapy, or for whom, in the opinion of the Investigator, no effective
             standard therapy exists, is tolerated or appropriate.

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

          -  Presence of at least one measurable lesion according to RECIST v1.1.

          -  Documented MAPK alteration

        Exclusion Criteria:

        - Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled
        in group 1 and 2 in the dose expansion part.

        Exceptions may be made after documented agreement between Novartis and Investigator.

          -  History or current evidence of retinal vein occlusion (RVO) or current risk factors
             for RVO.

          -  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.

          -  Patients receiving proton pump inhibitors which cannot be discontinued 3 days prior to
             the start study treatment and for the duration of the study.

          -  Pregnant or nursing (lactating) women

        Additional exclusion criteria for LXH254 in combination with PDR001

          -  History of severe hypersensitivity reactions, which in the opinion of the investigator
             may cause in increased risk of serious infusion reaction.

          -  Known human immunodeficiency virus (HIV).

          -  Any positive test for hepatitis B virus or hepatitis C virus indicating acute or
             chronic infection.

          -  Active, known or suspected autoimmune disease.

          -  Active infection requiring systemic antibiotic therapy

          -  Patients requiring systemic steroid therapy or any immunosuppressive therapy
             (≥10mg/day prednisone or equivalent) which cannot be discontinued at least 7 days
             prior to first dose of study treatment.

          -  Use of any live vaccines against infectious diseases within 4 weeks of initiation of
             study treatment.

        Other inclusion/exclusion criteria as per protocol may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity.
Time Frame:From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)
Safety Issue:
Description:cycle = 28 days

Secondary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Safety Issue:
Description:cycle = 28 days
Measure:Disease control rate (DCR)
Time Frame:Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Safety Issue:
Description:cycle = 28 days
Measure:Duration of response (DoR)
Time Frame:Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Safety Issue:
Description:cycle = 28 days
Measure:Progression-free survival (PFS)
Time Frame:Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months
Safety Issue:
Description:cycle = 28 days
Measure:Overall survival (OS) - only for dose expansion
Time Frame:From time of start treatment until the date of death; expected duration approximately 12 months
Safety Issue:
Description:cycle = 28 days
Measure:Plasma concentrations of LXH254
Time Frame:Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of LXH254: Area Under the Curve (AUC)
Time Frame:Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of LXH254: Peak Plasma Concentration (Cmax)
Time Frame:Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of LXH254: Time to Peak Plasma Concentration (Tmax)
Time Frame:Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of LXH254: half-life (T1/2)
Time Frame:Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor tissue and in blood
Time Frame:Cycle 1 day 1, 2, 3, 15, and 16; upon disease progression (expected duration approximately 12 months)
Safety Issue:
Description:cycle = 28 days
Measure:Plasma concentrations of PDR001
Time Frame:Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of PDR001: Area Under the Curve (AUC)
Time Frame:Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of PDR001: Peak Plasma Concentration (Cmax)
Time Frame:Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of PDR001: Time to Peak Plasma Concentration (Tmax)
Time Frame:Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Safety Issue:
Description:cycle = 28 days
Measure:Derived PK parameters of PDR001: half-life (T1/2)
Time Frame:Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Safety Issue:
Description:cycle = 28 days

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • LXH254, CRAF, MAPK, solid tumor, PDR001

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