for people ages 18 years and up (full criteria)
at San Diego, California and other locations
study started
completion around



To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.

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


Non-Small Cell Lung Cancer, Melanoma, NSCLC, 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, Lung Neoplasms, Non-Small-Cell Lung Carcinoma, Naporafenib, Ribociclib, LXH254+LTT462, LXH254+Trametinib, LXH254+Ribociclib


You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

-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


  • University of California San Diego .
    San Diego California 92103 United States
  • UCSF Medical Center
    San Francisco California 94143 United States


in progress, not accepting new patients
Start Date
Completion Date
Novartis Pharmaceuticals
Phase 1 research study
Study Type
About 241 people participating
Last Updated