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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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy 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. (Patients with KRAS mutant NSCLC with prior G12C inhibitor treatments are also excluded in the LXH254+trametinib expansion part). BRAF mutant patients group: Prior treatment with any EGFR, ALK, ROS1, KRAS, RAF (both BRAFV600 selective and pan-RAF), MEK1/2 and/or ERK1/2 inhibitors (for patients with BRAF V600 mutant NSCLC, prior treatments with BRAF and MEK1/2 inhibitors are allowed). Patients who have received more than 3 lines of anti-cancer therapy are excluded. - 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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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: LXH254
    LXH254 will be supplied as tablet for oral use.
  • Drug: Trametinib
    Trametinib will be supplied as film-coated tablet for oral use
Experimental
LXH254+Ribociclib
  • Drug: LXH254
    LXH254 will be supplied as tablet for oral use.
  • Drug: Ribociclib
    Ribociclib will be supplied in tablets and hard gelatin capsules.

More Details

Status
Active, not recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.