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

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02607813
First received: November 5, 2015
Last updated: June 30, 2017
Last verified: June 2017
  Purpose
A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.

Condition Intervention Phase
NSCLC Ovarian Cancer Melanoma Other Solid Tumors Drug: LXH254 Drug: PDR001 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

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) ]
    cycle = 28 days

  • Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only) [ Time Frame: 28 days ]
    cycle = 28 days

  • Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only) [ Time Frame: 56 days ]
    cycle =28 days


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 ]
    cycle = 28 days

  • Disease control rate (DCR) [ Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months ]
    cycle = 28 days

  • Duration of response (DoR) [ Time Frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months ]
    cycle = 28 days

  • Progression-free survival (PFS) [ Time Frame: Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months ]
    cycle = 28 days

  • Overall survival (OS) - only for dose expansion [ Time Frame: From time of start treatment until the date of death; expected duration approximately 12 months ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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) ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days

  • 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 ]
    cycle = 28 days


Estimated Enrollment: 174
Actual Study Start Date: January 18, 2016
Estimated Study Completion Date: March 14, 2019
Estimated Primary Completion Date: March 14, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escalation LXH254 Drug: LXH254
pan-RAF inhibitor
Experimental: Dose expansion LXH254: Group 1 Drug: LXH254
pan-RAF inhibitor
Experimental: Dose expansion LXH254: Group 2 Drug: LXH254
pan-RAF inhibitor
Experimental: Dose expansion LXH254: Group 3 Drug: LXH254
pan-RAF inhibitor
Experimental: Dose expansion: LXH254 + PDR001 Drug: LXH254
pan-RAF inhibitor
Drug: PDR001
Biological: PDR001 anti-PD1 antibody
Experimental: Dose escalation LXH254 + PDR001 Drug: LXH254
pan-RAF inhibitor
Drug: PDR001
Biological: PDR001 anti-PD1 antibody

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
United States, New York
Memorial Sloan Kettering Cancer Center SC - LXH254X2101 Recruiting
New York, New York, United States, 10021
Contact: Thrusha Chauhan       chauhant@mskcc.org   
Principal Investigator: Gopakumar Iyer         
United States, Texas
UT M.D Anderson Cancer Center SC - LXH254X2101 Recruiting
Houston, Texas, United States, 77030
Contact: Zehra Maloo    713-563-4426    zmaloo@mdanderson.org   
Principal Investigator: Filip Janku         
Canada, Ontario
Novartis Investigative Site Recruiting
Toronto, Ontario, Canada, M6G 1Z5
France
Novartis Investigative Site Recruiting
Toulouse Cedex 9, France, 31059
Germany
Novartis Investigative Site Recruiting
Heidelberg, Germany, 69120
Japan
Novartis Investigative Site Recruiting
Chuo-ku, Tokyo, Japan, 104-0045
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 03080
Netherlands
Novartis Investigative Site Recruiting
Groningen, Netherlands, 9713 GZ
Contact: Department of Pulmonary Diseases University Medical Center Groningen    +31 503611546    h.j.m.groen@umcg.nl   
Principal Investigator: H.J.M. Groen, M.D.         
Medical Oncology, Erasmus MC Recruiting
Rotterdam, Netherlands, 3075 CE
Contact       m.dejonge@erasmusmc.nl   
Principal Investigator: M. de Jonge, M.D.         
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Switzerland
Novartis Investigative Site Recruiting
Zuerich, Switzerland, 8091
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02607813     History of Changes
Other Study ID Numbers: CLXH254X2101
2015-003421-33 ( EudraCT Number )
Study First Received: November 5, 2015
Last Updated: June 30, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
LXH254, CRAF, MAPK, solid tumor, PDR001

ClinicalTrials.gov processed this record on July 21, 2017