Clinical Trial - NCT02607813

       

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

Recruiting

Sponsor: Novartis Pharmaceuticals

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02607813

Protocol Info

Short Description: Phase I of Oral LXH254 in Advanced Solid Tumors Harboring MAPK Pathway Alterations
Long Description: A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations
MGH Status: Open
Sponsor: Novartis
Disease Program: Thoracic

Next Steps


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Purpose

A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.
Condition Title Intervention Phase
NSCLC Ovarian Cancer Melanoma Other Solid Tumors LXH254 PDR001 Phase 1
Study Type Interventional
Official Title A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations

Primary Outcome Measures

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)] [Designated as safety issue: ]

Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only) [Time Frame: 28 days] [Designated as safety issue: ]

Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only) [Time Frame: 56 days] [Designated as safety issue: ]


Secondary Outcome Measures

Overall response rate (ORR) [Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months] [Designated as safety issue: ]

Disease control rate (DCR) [Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months] [Designated as safety issue: ]

Duration of response (DoR) [Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months] [Designated as safety issue: ]

Progression-free survival (PFS) [Time Frame: Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months] [Designated as safety issue: ]

Overall survival (OS) - only for dose expansion [Time Frame: From time of start treatment until the date of death; expected duration approximately 12 months] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Estimated Enrollment: 152
Study Start Date: January 2016
Estimated Study Completion Date: August 2020
Estimated Primary Completion Date: August 2020
Arms Assigned Interventions

Experimental:Dose escalation LXH254
Drug:LXH254
pan-RAF inhibitor

Experimental:Dose expansion LXH254: Group 1

Experimental:Dose expansion LXH254: Group 2

Experimental:Dose expansion LXH254: Group 3

Experimental:Dose expansion: LXH254 + PDR001
Drug:PDR001
Biological: PDR001 anti-PD1 antibody

Experimental:Dose escalation LXH254 + PDR001

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Additional inclusion criteria for the Dose Expansion part: LXH254 in combination with PDR001:

  • • Patients with confirmed KRAS-mutated NSCLC
  • • Patients with confirmed NRAS-mutated melanoma

Exclusion Criteria:

  • • Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled 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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02607813

Locations

  • United States, Massachusetts
    • Novartis Investigative Site Boston, Massachusetts, United States, 02114
  • United States, New York
    • Novartis Investigative Site New York, New York, United States, 10065
  • United States, Texas
    • UT M.D Anderson Cancer Center SC - LXH254X2101 Houston, Texas, United States, 77030
  • Canada, Ontario
    • Novartis Investigative Site Toronto, Ontario, Canada, M6G 1Z5
  • France,
    • Novartis Investigative Site Paris, , France, 75010
    • Novartis Investigative Site Toulouse Cedex 9, , France, 31059
  • Germany,
    • Novartis Investigative Site Essen, , Germany, 45147
    • Novartis Investigative Site Heidelberg, , Germany, 69120
  • Italy, MO
    • Novartis Investigative Site Modena, MO, Italy, 41124
  • Italy,
    • Novartis Investigative Site Napoli, , Italy, 80131
  • Japan, Tokyo
    • Novartis Investigative Site Chuo ku, Tokyo, Japan, 104 0045
  • Korea, Republic of,
    • Novartis Investigative Site Seoul, , Korea, Republic of, 03080
  • Netherlands,
    • Novartis Investigative Site Groningen, , Netherlands, 9713 GZ
    • Medical Oncology, Erasmus MC Rotterdam, , Netherlands, 3075 CE
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08035
  • Spain,
    • Novartis Investigative Site Madrid, , Spain, 28009
  • Switzerland,
    • Novartis Investigative Site Zuerich, , Switzerland, 8091

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02607813
Other Study ID Numbers: 2015-003421-33
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

LXH254, CRAF, MAPK, solid tumor, PDR001

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019