Clinical Trial - NCT02974725

       

A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma

Recruiting

Sponsor: Novartis Pharmaceuticals

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02974725

Protocol Info

Short Description: Phase 1 b LXH254 + TT462 in KRAS or BRAF mutant NSCLC
Long Description: A Phase Ib, open-label, multicenter study of oral LXH254-centric combinations in adult patients with advanced or metastatic KRAS or BRAF mutant Non-Small Cell Lung Cancer or NRAS mutant melanoma
MGH Status: Open
Sponsor: Novartis
Disease Program: Thoracic

Next Steps


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Purpose

To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.
Condition Title Intervention Phase
Non-Small Cell Lung Cancer Melanoma LXH254 LTT462 Trametinib LXH254 Ribociclib Phase 1
Study Type Interventional
Official Title A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma

Primary Outcome Measures

Number of participants with Adverse Events (AEs) as a measure of safety and tolerability [Time Frame: up to 5 years] [Designated as safety issue: ]

Dose limiting toxicities (DLTs) (dose escalation only) [Time Frame: up to 3 years] [Designated as safety issue: ]

Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions [Time Frame: up to 5 years] [Designated as safety issue: ]

Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity [Time Frame: Up to 5 years] [Designated as safety issue: ]


Secondary Outcome Measures

Overall Response Rate (ORR) [Time Frame: Up to 5 years] [Designated as safety issue: ]

Duration of response (DOR) [Time Frame: Up to 5 years] [Designated as safety issue: ]

Disease Control Rate (DCR) [Time Frame: Up to 5 years] [Designated as safety issue: ]

Progression Free Survival (PFS) [Time Frame: Up to 5 years] [Designated as safety issue: ]

Overall Survival (OS) - (dose expansion part only) [Time Frame: Up to 6 years] [Designated as safety issue: ]

Derived PK parameter (Cmax) for LXH254 & LTT462: [Time Frame: Up to 5 years] [Designated as safety issue: ]

Derived PK parameter (AUC) for LXH254 & LTT462 [Time Frame: Up to 5 years] [Designated as safety issue: ]

Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples [Time Frame: up to 5 years] [Designated as safety issue: ]

Derived PK parameter (Cmax) for LXH254 & trametinib [Time Frame: up to 5 years] [Designated as safety issue: ]

Derived PK parameter (AUC) for LXH254 & trametinib [Time Frame: Up to 5 years] [Designated as safety issue: ]

Derived PK parameter (Cmax) for LXH254 & ribociclib [Time Frame: Up to 5 years] [Designated as safety issue: ]

Derived PK parameter (AUC) for LXH254 & ribociclib [Time Frame: Up to 5 years] [Designated as safety issue: ]

Estimated Enrollment: 315
Study Start Date: February 2017
Estimated Study Completion Date: May 2022
Estimated Primary Completion Date: January 2022
Arms Assigned Interventions

Experimental:LXH254+LTT462
Drug:LTT462
LTT462 will be supplied as hard gelatin capsule for oral use.

Experimental:LXH254+Trametinib
Drug:LXH254
Trametinib will be supplied as film-coated tablet for oral use

Experimental:LXH254+Ribociclib
Drug:Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules.

Eligibility

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

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • • Patients must have advanced or metastatic NSCLC or cutaneous melanoma
  • • Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (cutaneous melanoma) in tumor tissue
  • • All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
  • • ECOG (Eastern Cooperative Oncology Group) performance status = 2

Exclusion Criteria:

  • • Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. BRAF mutant patients group: Prior treatment with an ERKi and/or a pan-RAFi.
  • • 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 (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
  • • Patients with Gilbert's syndrome or other heritable diseases of bile processing.

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02974725

Locations

  • United States, California
    • University of California San Diego San Diego, California, United States, 92103
    • UCSF Medical Center San Francisco, California, United States, 94143
  • United States, Massachusetts
    • Massachusetts General Hospital SC Boston, Massachusetts, United States, 02114
  • United States, Tennessee
    • Sarah Cannon Research Institute Tennessee Oncology Nashville, Tennessee, United States, 37203
  • United States, Texas
    • University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030
  • Australia, New South Wales
    • Novartis Investigative Site Westmead, New South Wales, Australia, 2145
  • Australia, Victoria
    • Novartis Investigative Site Melbourne, Victoria, Australia, 3000
    • Novartis Investigative Site Prahran, Victoria, Australia, 3181
  • Belgium,
    • Novartis Investigative Site Leuven, , Belgium, 3000
  • France,
    • Novartis Investigative Site Paris Cedex 10, , France, 75475
    • Novartis Investigative Site Villejuif Cedex, , France, 94800
  • Germany,
    • Novartis Investigative Site Dresden, , Germany, 01307
    • Novartis Investigative Site Essen, , Germany, 45147
    • Novartis Investigative Site Frankfurt, , Germany, 60590
    • Novartis Investigative Site Koeln, , Germany, 50937
  • Italy, MI
    • Novartis Investigative Site Milano, MI, Italy, 20133
    • Novartis Investigative Site Milano, MI, Italy, 20162
    • Novartis Investigative Site Rozzano, MI, Italy, 20089
  • Italy, VR
    • Novartis Investigative Site Verona, VR, Italy, 37126
  • Italy,
    • Novartis Investigative Site Napoli, , Italy, 80131
  • Korea, Republic of,
    • Novartis Investigative Site Seoul, , Korea, Republic of, 03080
    • Novartis Investigative Site Seoul, , Korea, Republic of, 06351
  • Poland,
    • Novartis Investigative Site Warszawa, , Poland, 02 781
  • Spain, Andalucia
    • Novartis Investigative Site Sevilla, Andalucia, Spain, 41013
  • Spain, Catalunya
    • Novartis Investigative Site Barcelona, Catalunya, Spain, 08036
  • Spain, Comunidad Valenciana
    • Novartis Investigative Site Valencia, Comunidad Valenciana, Spain, 46010
  • Spain, Navarra
    • Novartis Investigative Site Pamplona, Navarra, Spain, 31008
  • Spain,
    • Novartis Investigative Site Barcelona, , Spain, 08035
    • Novartis Investigative Site Madrid, , Spain, 28034
  • Sweden,
    • Novartis Investigative Site Stockholm, , Sweden, 171 76

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02974725
Other Study ID Numbers: 2016-004293-18
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Novartis:

NSCLC

Melanoma

NRAS

KRAS

BRAF

LXH254

LTT462

Trametinib

Ribocliclib

Non-small cell lung carcinoma (NSCLC)

treatment of lung cancer after first metastasis

lung cancer

lung adenocarcinoma

Large-cell lung carcinoma

Non small cell lung carcinoma

Non small cell lung cancer

Large cell lung carcinoma

Large cell lung cancer

squamous cell lung carcinoma

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Melanoma

Trametinib

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 January 14, 2021