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Study of LXH254 and LTT462 in NSCLC

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ClinicalTrials.gov Identifier: NCT02974725
Recruitment Status : Recruiting
First Posted : November 28, 2016
Last Update Posted : October 26, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 and LTT462 combination and for the LXH254 and trametinib combination.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Melanoma Drug: LXH254 Drug: LTT462 Drug: Trametinib Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 127 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-label, Multicenter Study of Oral LXH254 in Combination With Oral LTT462 in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer
Actual Study Start Date : February 24, 2017
Estimated Primary Completion Date : June 17, 2019
Estimated Study Completion Date : June 29, 2020


Arm Intervention/treatment
Experimental: LXH254+LTT462 Drug: LXH254
LXH254 will be supplied as tablet for oral use.

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

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

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




Primary Outcome Measures :
  1. Number of participants with Adverse Events (AEs) as a measure of safety and tolerability [ Time Frame: 12 months ]
  2. Dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: 1 cycle (28 days) ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 12 months ]
  2. Duration of response (DOR) [ Time Frame: Up to 12 months ]
  3. Disease Control Rate (DCR) [ Time Frame: Up to 12 months ]
  4. Progression Free Survival (PFS) [ Time Frame: Up to 12 months ]
  5. Overall Survival (OS) - (dose expansion part only) [ Time Frame: Up to 12 months ]
  6. Plasma concentrations of LXH254 [ Time Frame: Up to Month 5 ]
  7. Plasma concentrations of LTT462 [ Time Frame: Up to Month 5 ]
  8. Derived PK parameter (Cmax) for LXH254 & LTT462: [ Time Frame: Up to Month 5 ]
  9. Derived PK parameter (AUC) for LXH254 & LTT462 [ Time Frame: Up to Month 5 ]
  10. Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples [ Time Frame: baseline, month 12 ]
  11. Plasma concentrations of trametinib [ Time Frame: Up to Month 5 ]
  12. Derived PK parameter (Cmax) for LXH254 & trametinib [ Time Frame: Up to Month 5 ]
  13. Derived PK parameter (AUC) for LXH254 & trametinib [ Time Frame: Up to Month 5 ]


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

Inclusion Criteria:

  • Patients must have advanced or metastatic NSCLC or melanoma
  • Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02974725


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

Locations
United States, Massachusetts
Novartis Investigative Site Recruiting
Boston, Massachusetts, United States, 02114
Contact: Bakhan Barzangy    617-726-1849    bbarzangy@mgh.harvard.edu   
Principal Investigator: Rebecca Heist         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Belgium
Novartis Investigative Site Recruiting
Leuven, Belgium, 3000
France
Novartis Investigative Site Recruiting
Villejuif Cedex, France, 94805
Germany
Novartis Investigative Site Recruiting
Frankfurt, Germany, 60590
Novartis Investigative Site Recruiting
Koeln, Germany, 50937
Italy
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08036
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02974725     History of Changes
Other Study ID Numbers: CLXH254X2102
2016-004293-18 ( EudraCT Number )
First Posted: November 28, 2016    Key Record Dates
Last Update Posted: October 26, 2018
Last Verified: October 2018
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 ):
NSCLC
Melanoma
NRAS
KRAS
BRAF
LXH254
LTT462
Trametinib
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
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action