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

April 9, 2025 updated by: Novartis Pharmaceuticals

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

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

241

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Novartis Investigative Site
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Novartis Investigative Site
  • Belgium
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • France
      • Lyon, France, 69373
        • Novartis Investigative Site
      • Paris 10, France, 75475
        • Novartis Investigative Site
      • Villejuif, France, 94800
        • Novartis Investigative Site
  • Germany
      • Dresden, Germany, 01307
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Frankfurt, Germany, 60590
        • Novartis Investigative Site
      • Koeln, Germany, 50937
        • Novartis Investigative Site
  • Israel
      • Tel Aviv, Israel, 6423906
        • Novartis Investigative Site
  • Italy
      • Napoli, Italy, 80131
        • Novartis Investigative Site
    • MI
      • Milano, MI, Italy, 20162
        • Novartis Investigative Site
      • Milano, MI, Italy, 20133
        • Novartis Investigative Site
      • Rozzano, MI, Italy, 20089
        • Novartis Investigative Site
    • VR
      • Verona, VR, Italy, 37126
        • Novartis Investigative Site
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Novartis Investigative Site
      • Seoul, Korea, Republic of, 06351
        • Novartis Investigative Site
  • Poland
      • Warszawa, Poland, 02 781
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28034
        • Novartis Investigative Site
    • Andalucia
      • Sevilla, Andalucia, Spain, 41013
        • Novartis Investigative Site
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
      • Barcelona, Catalunya, Spain, 08036
        • Novartis Investigative Site
    • Comunidad Valenciana
      • Valencia, Comunidad Valenciana, Spain, 46010
        • Novartis Investigative Site
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Novartis Investigative Site
  • Sweden
      • Stockholm, Sweden, 171 76
        • Novartis Investigative Site
  • United States
    • California
      • San Diego, California, United States, 92103
        • University of California San Diego .
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital SC
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Ctr .
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute Tennessee Oncology
    • Texas
      • Houston, Texas, United States, 77030
        • Uni Of TX MD Anderson Cancer Cntr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
Time Frame: up to 5 years
up to 5 years
Dose limiting toxicities (DLTs) (dose escalation only)
Time Frame: up to 3 years
up to 3 years
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
up to 5 years
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
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease Control Rate (DCR)
Time Frame: Up to 5 years
Up to 5 years
Overall Response Rate (ORR)
Time Frame: Up to 5 years
Up to 5 years
Duration of response (DOR)
Time Frame: Up to 5 years
Up to 5 years
Progression Free Survival (PFS)
Time Frame: Up to 5 years
Up to 5 years
Derived PK parameter (Cmax) for LXH254 & LTT462:
Time Frame: Up to 5 years
Up to 5 years
Derived PK parameter (AUC) for LXH254 & LTT462
Time Frame: Up to 5 years
Up to 5 years
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples
Time Frame: up to 5 years
up to 5 years
Derived PK parameter (Cmax) for LXH254 & trametinib
Time Frame: up to 5 years
up to 5 years
Derived PK parameter (AUC) for LXH254 & trametinib
Time Frame: Up to 5 years
Up to 5 years
Derived PK parameter (Cmax) for LXH254 & ribociclib
Time Frame: Up to 5 years
Up to 5 years
Derived PK parameter (AUC) for LXH254 & ribociclib
Time Frame: Up to 5 years
Up to 5 years
Overall Survival (OS) - (dose expansion part only)
Time Frame: Up to 5 years
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 24, 2017

Primary Completion (Actual)

April 24, 2024

Study Completion (Actual)

April 24, 2024

Study Registration Dates

First Submitted

November 23, 2016

First Submitted That Met QC Criteria

November 23, 2016

First Posted (Estimated)

November 28, 2016

Study Record Updates

Last Update Posted (Actual)

April 13, 2025

Last Update Submitted That Met QC Criteria

April 9, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLXH254X2102
  • 2016-004293-18 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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