Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT04417621 |
Recruitment Status :
Recruiting
First Posted : June 4, 2020
Last Update Posted : February 24, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Melanoma | Drug: LXH254 Drug: LTT462 Drug: Trametinib Drug: Ribociclib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 320 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | October 30, 2020 |
Estimated Primary Completion Date : | April 27, 2023 |
Estimated Study Completion Date : | April 27, 2023 |

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: Trametinib
Trametinib will be supplied as film-coated tablet for oral use |
Experimental: LXH254 + ribociclib |
Drug: Ribociclib
Ribociclib will be supplied in tablets and hard gelatin capsules. |
- Overall Response Rate [ Time Frame: 35 months ]Confirmed ORR using RECIST v1.1, per local assessment
- Duration of Reposnse (DOR) [ Time Frame: 4 years ]Local and central assessment
- Progression Free Survival (PFS) [ Time Frame: 4 years ]
- Disease Control Rate (DCR) [ Time Frame: 3 years ]Using RECIST v1.1, per local and central assessment
- Overall Survival (OS) [ Time Frame: 4 years ]
- Derived PK parameter (Cmax) for LXH254 & LTT462 [ Time Frame: Up to 5 months ]
- Derived PK parameter (Cmax) for LXH254 & trametinib [ Time Frame: Up to 5 months ]
- Derived PK parameter (Cmax) for LXH254 & ribociclib [ Time Frame: Up to 5 months ]
- Derived PK parameter (AUC) for LXH254 & LTT462 [ Time Frame: Up to 5 months ]
- Derived PK parameter (AUC) for LXH254 & trametinib [ Time Frame: Up to 5 months ]
- Derived PK parameter (AUC) for LXH254 & ribociclib [ Time Frame: Up to 5 months ]
- Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 35 months ]Number of participants with Adverse Events (AEs) and SAEs as a measure of safety and tolerability
- Dose Interruptions [ Time Frame: 35 months ]Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
- Dose reductions [ Time Frame: 35 months ]Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 12 Years to 120 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04417621
Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
Contact: Novartis Pharmaceuticals | +41613241111 |
United States, California | |
The Angeles Clinic and Research Institute | Recruiting |
Los Angeles, California, United States, 90025 | |
Principal Investigator: Omid Hamid | |
University of California Los Angeles | Recruiting |
Los Angeles, California, United States, 90095 | |
Contact: Jose Cruz Ramon Rangel Cordero JRangelCordero@mednet.ucla.edu | |
Principal Investigator: Bartosz Chmielowski | |
United States, Florida | |
Florida Cancer Specialists Sarasota Office | Recruiting |
Fort Myers, Florida, United States, 33901 | |
Contact: Jill Martin 941-377-9993 Jill.Martin@flcancer.com | |
Principal Investigator: Manish Patel | |
University of Miami | Recruiting |
Miami, Florida, United States, 33136 | |
Contact 305-243-6823 | |
Principal Investigator: Jose Lutzky | |
United States, Massachusetts | |
Massachusetts General Hospital Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Principal Investigator: Ryan Sullivan | |
Dana Farber Cancer Institute Dept.of DFCI | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Contact: Wilhelmia Wagner wilhelminar_wagner@dfci.harvard.edu | |
Principal Investigator: Megan Insco | |
United States, Minnesota | |
Mayo Clinic Mayo Rochester | Recruiting |
Rochester, Minnesota, United States, 55905 | |
Contact 507-284-2511 | |
Principal Investigator: Anastasios Dimou | |
United States, New York | |
Memorial Sloan Kettering Dept. of MSKCC | Recruiting |
New York, New York, United States, 10017 | |
Contact: Natasha Martin 646-227-2157 martinn@mskcc.org | |
Principal Investigator: Alexander Shoushtari | |
United States, Pennsylvania | |
University of Pittsburgh Medical Center | Recruiting |
Pittsburgh, Pennsylvania, United States, 15213 | |
Contact 412-623-7707 | |
Principal Investigator: Yana Najjar | |
United States, Texas | |
University of TX MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Krysta McVay 713-745-1936 KKMcVay@mdanderson.org | |
Principal Investigator: Rodabe N Amaria | |
Australia, New South Wales | |
Novartis Investigative Site | Recruiting |
North Sydney, New South Wales, Australia, 2060 | |
Australia, Queensland | |
Novartis Investigative Site | Recruiting |
Wooloongabba, Queensland, Australia, 4102 | |
Austria | |
Novartis Investigative Site | Recruiting |
Salzburg, Austria, 5020 | |
Belgium | |
Novartis Investigative Site | Recruiting |
Wilrijk, Belgium, 2610 | |
France | |
Novartis Investigative Site | Recruiting |
Lille Cedex, France, 59037 | |
Novartis Investigative Site | Recruiting |
Marseille Cedex 9, France, 13913 | |
Novartis Investigative Site | Recruiting |
Paris Cedex 10, France, 75475 | |
Novartis Investigative Site | Recruiting |
Pierre Benite Cedex, France, 69495 | |
Israel | |
Novartis Investigative Site | Recruiting |
Ramat Gan, Israel, 52621 |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT04417621 |
Other Study ID Numbers: |
CLXH254C12201 |
First Posted: | June 4, 2020 Key Record Dates |
Last Update Posted: | February 24, 2021 |
Last Verified: | February 2021 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
LXH254 Melanoma NRAS BRAF |
LTT462 Trametinib Ribocliclib |
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue |
Nevi and Melanomas Trametinib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |