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: May 19, 2022

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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
Start date 
Oct 30, 2020
Completion date 
Oct 14, 2022
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 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.

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.
≤ 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.

Other protocol-defined exclusion criteria may apply

Study Locations

United States
The Angeles Clinic and Research Institute
Recruiting
Los Angeles, 90025 - California
Contact: Joslyn Cabral - [email protected] - Omid Hamid
United States
University of California Los Angeles
Recruiting
Los Angeles, 90095 - California
Contact: Jose Cruz Ramon Rangel Cordero - [email protected] - Bartosz Chmielowski
United States
Florida Cancer Specialists Sarasota Office
Recruiting
Fort Myers, 33901 - Florida
Contact: Donna Jones (941-377-9993) - [email protected] - Manish Patel
United States
University of Miami
Recruiting
Miami, 33136 - Florida
Contact: (305-243-6823) Jose Lutzky
United States
Massachusetts General Hospital Massachusetts General Hospital
Recruiting
Boston, 02114 - Massachusetts
Contact: Nadine Erickson - [email protected] - Ryan Sullivan
United States
Dana Farber Cancer Institute Dept.of DFCI
Recruiting
Boston, 02215 - Massachusetts
Contact: Michael Manos - [email protected] - Megan Insco
United States
Mayo Clinic Mayo Rochester
Recruiting
Rochester, 55905 - Minnesota
Contact: Clinical Trials Referral Office (855-776-0015) - [email protected] - Anastasios Dimou
United States
NYU Laura and Isaac Perlmutter Cancer Center
Recruiting
New York, 10016 - New York
Contact: David Mossa (212-263-9959) - [email protected] - Janice Mehnert
United States
Memorial Sloan Kettering Dept. of MSKCC
Recruiting
New York, 10017 - New York
Contact: Olivia Gibson (646-227-2157) - [email protected] - Alexander Shoushtari
United States
University of Pittsburgh Medical Center
Recruiting
Pittsburgh, 15213 - Pennsylvania
Contact: Sarah Barnick (412-623-7707) - [email protected] - Yana Najjar
United States
Argentina
Novartis Investigative Site
Recruiting
Caba, C1426ANZ
Buenos Aires
Argentina
Novartis Investigative Site
Recruiting
Buenos Aires, C1125ABE
-
Argentina
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 05, 13885
-
France
Novartis Investigative Site
Recruiting
Paris Cedex 10, 75475
-
France
Novartis Investigative Site
Recruiting
Toulouse Cedex 9, 31059
-
France
Novartis Investigative Site
Recruiting
Villejuif Cedex, 94800
-
France
Italy
Novartis Investigative Site
Recruiting
Milano, 20141
MI
Italy
Switzerland
Novartis Investigative Site
Recruiting
Zuerich, 8091
-
Switzerland
United Kingdom
Novartis Investigative Site
Recruiting
Cambridge, CB2 2QQ
-
United Kingdom
Novartis Investigative Site
Recruiting
London, NW1 2BU
-
United Kingdom
Novartis Investigative Site
Recruiting
Manchester, M20 2BX
-
United Kingdom
Novartis Investigative Site
Recruiting
Oxford, OX3 7LJ
-
United Kingdom

Contacts

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

Have a question?

Call 1-888-669-6682 or email [email protected]