MelanomaPhase 2NCT04417621
Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
A Phase 2 study testing LXH254, LTT462 and Trametinib in people with Melanoma, run by Novartis Pharmaceuticals at 36 sites in 12 countries.
Trial summary
The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma Read more about this study
- Who is it for?
- Ages 12 to 120 years
- Conditions the study is for
- Melanoma
- What is being tested?
- LXH254, LTT462 and Trametinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 36 sitesin 12 countries
- Study dates
- 30 Oct 2020to 2 Feb 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 120 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
36 sites in 12 countries.
36 sites in 12 countries
United States12 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Florida Cancer Specialists
Fort Myers, Florida, 33901
Univ of TX MD Anderson Cancer Cntr
Houston, Texas, 77030
The Angeles Clinic and Research Institute
Los Angeles, California, 90025
NYU Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016
Memorial Sloan Kettering
New York, New York, 10017
University of Pittsburgh Med Center
Pittsburgh, Pennsylvania, 15213
Mayo Clinic Mayo Rochester
Rochester, Minnesota, 55905
Mayo Clinic Rochester
Rochester, Minnesota, 55905
UCSF Medical Center
San Francisco, California, 94143
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
France6 sites
Novartis Investigative Site
Lille, 59037
Novartis Investigative Site
Marseille, 13885
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Pierre-Bénite, 69495
Novartis Investigative Site
Toulouse, 31059
Novartis Investigative Site
Villejuif, 94800
Germany4 sites
Novartis Investigative Site
Dresden, Saxony, 01307
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Heidelberg, 69120
Novartis Investigative Site
Tübingen, 72076
Australia3 sites
Novartis Investigative Site
North Sydney, New South Wales, 2060
Novartis Investigative Site
Subiaco, Western Australia, 6008
Novartis Investigative Site
Wooloongabba, Queensland, 4102
Belgium2 sites
Novartis Investigative Site
Leuven, 3000
Novartis Investigative Site
Wilrijk, 2610
Italy2 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Naples, 80131
Switzerland2 sites
Novartis Investigative Site
Lausanne, 1011
Novartis Investigative Site
Zurich, 8091
Netherlands1 site
Novartis Investigative Site
Maastricht, Limburg, 6229 HX
About this study
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
The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma
- Conditions
- Melanoma
- Being tested
- LXH254, LTT462, Trametinib, Ribociclib
- Keywords
- LXH254, Melanoma, NRAS, BRAF, LTT462, Trametinib, Ribocliclib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LXH254Drug
LXH254 will be supplied as tablet for oral use.
LTT462Drug
LTT462 will be supplied as hard gelatin capsule for oral use.
TrametinibDrug
Trametinib will be supplied as film-coated tablet for oral use
RibociclibDrug
Ribociclib will be supplied in tablets and hard gelatin capsules.
| Study group | Role | What they receive |
|---|---|---|
| LXH254 + LTT462 | Experimental | Not described Receives: Drug: LXH254; Drug: LTT462 |
| LXH254 + trametinib | Experimental | Not described Receives: Drug: Trametinib |
| LXH254 + ribociclib | Experimental | Not described Receives: Drug: Ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Confirmed ORR using RECIST v1.1, per local assessment
Measured: 35 months
Secondary outcomes (13)
Duration of Reposnse (DOR)
Local and central assessment
Measured: 4 years
Progression Free Survival (PFS)
Measured: 4 years
Disease Control Rate (DCR)
Using RECIST v1.1, per local and central assessment
Measured: 3 years
Overall Survival (OS)
Measured: 4 years
Derived PK parameter (Cmax) for LXH254 & LTT462
Measured: Up to 5 months
Derived PK parameter (Cmax) for LXH254 & trametinib
Measured: Up to 5 months
Derived PK parameter (Cmax) for LXH254 & ribociclib
Measured: Up to 5 months
Derived PK parameter (AUC) for LXH254 & LTT462
Measured: Up to 5 months
Derived PK parameter (AUC) for LXH254 & trametinib
Measured: Up to 5 months
Derived PK parameter (AUC) for LXH254 & ribociclib
Measured: Up to 5 months
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Number of participants with Adverse Events (AEs) and SAEs as a measure of safety and tolerability
Measured: 35 months
Dose Interruptions
Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Measured: 35 months
Dose reductions
Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Measured: 35 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2020
- Study start30 Oct 2020
- Primary completion2 Feb 2027 (estimated)
- Study completion2 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04417621
- Sponsor's protocol ID
- CLXH254C12201
- Other IDs
- 2020-000873-26
- Status last verified
- Mar 2026
- First submitted
- 3 Jun 2020
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 35587446
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04417621
- Acronym / sponsor ID
- CLXH254C12201
- Conditions
- Melanoma
- Keywords
- LXH254, Melanoma, NRAS, BRAF, LTT462, Trametinib, Ribocliclib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 30 Oct 2020 (actual)
- Primary completion
- 2 Feb 2027 (estimated)
- Study completion
- 2 Feb 2027 (estimated)
- First posted
- 4 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LXH254 + LTT462 | Experimental | Drug: LXH254, Drug: LTT462 |
| LXH254 + trametinib | Experimental | Drug: Trametinib |
| LXH254 + ribociclib | Experimental | Drug: Ribociclib |
Who may qualify
- Ages
- 12 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female must be ≥ 12 years For adolescents only (12-17 years): body weight > 40kg Histologically confirmed unresectable or metastatic cutaneous 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LXH254LXH254 will be supplied as tablet for oral use. | Drug | LXH254 + LTT462 |
| LTT462LTT462 will be supplied as hard gelatin capsule for oral use. | Drug | LXH254 + LTT462 |
| TrametinibTrametinib will be supplied as film-coated tablet for oral use | Drug | LXH254 + trametinib |
| RibociclibRibociclib will be supplied in tablets and hard gelatin capsules. | Drug | LXH254 + ribociclib |
Primary outcome
Overall Response Rate
Time frame: 35 months
Confirmed ORR using RECIST v1.1, per local assessment
13 secondary outcomes
Duration of Reposnse (DOR)
Time frame: 4 years
Progression Free Survival (PFS)
Time frame: 4 years
Disease Control Rate (DCR)
Time frame: 3 years
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
Dose Interruptions
Time frame: 35 months
Dose reductions
Time frame: 35 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2026.
- Derived from this study: PubMed 35587446Moschos 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
36 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LXH254, LTT462 and Trametinib in people with Melanoma, run by Novartis Pharmaceuticals at 36 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in United States, France, Germany, Australia, Belgium and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: 35 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04417621, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2026.