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

ClinicalTrials.gov Identifier: NCT04417621

Novartis Reference Number: CLXH254C12201

Last Update: Mar 18, 2021

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma

Condition 
Melanoma
Phase 
Phase 2
Overall status 
Recruiting
Enrollment count 
320 participants
Start date 
Oct 30, 2020
Completion date 
Apr 27, 2023
Gender 
All
Age(s)
12 Years - 120 Years (Child, Adult, Older Adult)

Interventions

Drug
LXH254
LXH254 will be supplied as tablet for oral use.
Drug
LTT462
LTT462 will be supplied as hard gelatin capsule for oral use.
Drug
Trametinib
Trametinib will be supplied as film-coated tablet for oral use
Drug
Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules.

Eligibility Criteria

Inclusion Criteria:

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 an anti-PD-1/PD-L1 checkpoint inhibitor as a single agent or in combination with anti-CTLA-4. No additional systemic treatment is allowed for unresectable or metastatic melanoma
A maximum of two prior lines of systemic immunotherapy for unresectable or metastatic melanoma are allowed
The last dose of prior therapy (anti-PD-1, anti-PD-L1 or anti-CTLA-4) must have been received more than four weeks before randomization
Participants must have documented confirmed progressive disease as per RECIST v1.1 while on/after treatment with checkpoint inhibitor therapy. The last progression must have occurred within 12 weeks prior to randomization in the study
Participants with BRAFV600 mutant disease:
Participants must have received prior systemic therapy for unresectable or metastatic melanoma with anti-PD-1/PD-L1 as a single agent or in combination with anti-CTLA-4. Additionally, participants must have received targeted therapy with a RAFi as a single agent or in combination with a MEKi as the last prior therapy. No additional systemic treatment is allowed for advanced or metastatic melanoma
A maximum of three prior lines of systemic therapy for unresectable or metastatic melanoma are allowed
The last dose of targeted therapy (last prior therapy) must have been received more than 2 weeks prior to randomization
Participants must have documented progressive disease as per RECIST v1.1 while on/after treatment with targeted therapy. The last progression must have occurred within 12 weeks prior to randomization in the study Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

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.
≤ 4 weeks or ≤ 5 half-life (whichever is shorter) for small molecule therapeutics.
≤ 4 weeks for any immunotherapy treatment including immune checkpoint inhibitors.

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.

Other protocol-defined exclusion criteria may apply

Study Locations

United States
The Angeles Clinic and Research Institute
Recruiting
Los Angeles, 90025
California
United States
University of California Los Angeles
Recruiting
Los Angeles, 90095
California
United States
Florida Cancer Specialists Sarasota Office
Recruiting
Fort Myers, 33901
Florida
United States
University of Miami
Recruiting
Miami, 33136
Florida
United States
Massachusetts General Hospital Massachusetts General Hospital
Recruiting
Boston, 02114
Massachusetts
United States
Dana Farber Cancer Institute Dept.of DFCI
Recruiting
Boston, 02215
Massachusetts
United States
Mayo Clinic Mayo Rochester
Recruiting
Rochester, 55905
Minnesota
United States
NYU Laura and Isaac Perlmutter Cancer Center
Recruiting
New York, 10016
New York
United States
Memorial Sloan Kettering Dept. of MSKCC
Recruiting
New York, 10017
New York
United States
University of Pittsburgh Medical Center
Recruiting
Pittsburgh, 15213
Pennsylvania
United States
University of TX MD Anderson Cancer Center
Recruiting
Houston, 77030
Texas
United States
Australia
Novartis Investigative Site
Recruiting
North Sydney, 2060
New South Wales
Australia
Novartis Investigative Site
Recruiting
Wooloongabba, 4102
Queensland
Australia
Austria
Novartis Investigative Site
Recruiting
Salzburg, 5020
-
Austria
Belgium
Novartis Investigative Site
Recruiting
Leuven, 3000
-
Belgium
Novartis Investigative Site
Recruiting
Wilrijk, 2610
-
Belgium
France
Novartis Investigative Site
Recruiting
Lille Cedex, 59037
-
France
Novartis Investigative Site
Recruiting
Marseille Cedex 9, 13913
-
France
Novartis Investigative Site
Recruiting
Paris Cedex 10, 75475
-
France
Novartis Investigative Site
Recruiting
Pierre Benite Cedex, 69495
-
France
Novartis Investigative Site
Recruiting
Toulouse Cedex 9, 31059
-
France
Novartis Investigative Site
Recruiting
Villejuif Cedex, 94800
-
France
Israel
Novartis Investigative Site
Recruiting
Ramat Gan, 52621
-
Israel
Norway
Novartis Investigative Site
Recruiting
Oslo, 0379
-
Norway

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

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