Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
A Randomized, Open-label, Multi-arm, Two-part, Phase II Study to Assess Efficacy and Safety of Multiple LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic BRAFV600 or NRAS Mutant Melanoma
2 other identifiers
interventional
134
12 countries
36
Brief Summary
The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2020
Longer than P75 for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 3, 2020
CompletedFirst Posted
Study publicly available on registry
June 4, 2020
CompletedStudy Start
First participant enrolled
October 30, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 2, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 2, 2027
March 12, 2026
March 1, 2026
6.3 years
June 3, 2020
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Response Rate
Confirmed ORR using RECIST v1.1, per local assessment
35 months
Secondary Outcomes (13)
Duration of Reposnse (DOR)
4 years
Progression Free Survival (PFS)
4 years
Disease Control Rate (DCR)
3 years
Overall Survival (OS)
4 years
Derived PK parameter (Cmax) for LXH254 & LTT462
Up to 5 months
- +8 more secondary outcomes
Study Arms (3)
LXH254 + LTT462
EXPERIMENTALLXH254 + trametinib
EXPERIMENTALLXH254 + ribociclib
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- Male or female must be ≥ 12 years For adolescents only (12-17 years): body weight \> 40kg Histologically confirmed unresectable or metastatic cutaneous melanoma
- Previously treated for unresectable or metastatic melanoma:
- Participants with NRAS mutation:
- Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents.
- A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents administered with CPI are permitted.
- To rule out pseudo-progression, participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. Confirmation is not required for patients who remained on treatment for \>6 months.
- Participants with BRAFV600 mutant disease:
- Participants must have received prior systemic therapy for unresectable or metastatic melanoma with checkpoint inhibitors (CPI), either an anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4, investigational agents, chemotherapy or locally directed anti-neoplastic agents. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi (+/- CPI allowed) as the last prior therapy.
- A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents with CPI are permitted.
- A maximum of one line of targeted therapy is allowed, and it must be the most recent line of therapy.
- Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy.
You may not qualify if:
- Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
- ≤ 4 weeks for radiation therapy or ≤ 2 weeks for limited field radiation for palliation prior to the first dose of study treatment.
- ≤ 2 weeks for small molecule therapeutics.
- ≤ 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.
- ≤ 4 weeks for chemotherapy agents, locally directed anti-neoplastic agents, or other investigational agents.
- ≤ 6 weeks for cytotoxic agents with major delayed toxicities, such as nitrosourea and mitomycin c.
- Participants participating in additional parallel investigational drug or medical device studies.
- All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are neurologically unstable History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (36)
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
UCSF Medical Center
San Francisco, California, 94143, United States
Florida Cancer Specialists
Fort Myers, Florida, 33901, United States
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Mayo Clinic Mayo Rochester
Rochester, Minnesota, 55905, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
NYU Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016, United States
Memorial Sloan Kettering
New York, New York, 10017, United States
University of Pittsburgh Med Center
Pittsburgh, Pennsylvania, 15213, United States
Univ of TX MD Anderson Cancer Cntr
Houston, Texas, 77030, United States
Novartis Investigative Site
CABA, Buenos Aires, C1426ANZ, Argentina
Novartis Investigative Site
North Sydney, New South Wales, 2060, Australia
Novartis Investigative Site
Wooloongabba, Queensland, 4102, Australia
Novartis Investigative Site
Subiaco, Western Australia, 6008, Australia
Novartis Investigative Site
Leuven, 3000, Belgium
Novartis Investigative Site
Wilrijk, 2610, Belgium
Novartis Investigative Site
Lille, 59037, France
Novartis Investigative Site
Marseille, 13885, France
Novartis Investigative Site
Paris, 75475, France
Novartis Investigative Site
Pierre-Bénite, 69495, France
Novartis Investigative Site
Toulouse, 31059, France
Novartis Investigative Site
Villejuif, 94800, France
Novartis Investigative Site
Dresden, Saxony, 01307, Germany
Novartis Investigative Site
Essen, 45147, Germany
Novartis Investigative Site
Heidelberg, 69120, Germany
Novartis Investigative Site
Tübingen, 72076, Germany
Novartis Investigative Site
Ramat Gan, 5265601, Israel
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Naples, 80131, Italy
Novartis Investigative Site
Maastricht, Limburg, 6229 HX, Netherlands
Novartis Investigative Site
Oslo, 0310, Norway
Novartis Investigative Site
Lausanne, 1011, Switzerland
Novartis Investigative Site
Zurich, 8091, Switzerland
Novartis Investigative Site
Manchester, M20 2BX, United Kingdom
Related Publications (1)
Moschos SJ. War against NRAS-Mutant Melanoma Using Targeted Therapies Remains Challenging. Clin Cancer Res. 2022 Jul 15;28(14):2977-2979. doi: 10.1158/1078-0432.CCR-22-1256.
PMID: 35587446DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 3, 2020
First Posted
June 4, 2020
Study Start
October 30, 2020
Primary Completion (Estimated)
February 2, 2027
Study Completion (Estimated)
February 2, 2027
Last Updated
March 12, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.