Non-Small Cell Lung CancerPhase 1NCT02974725
A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma
A Phase 1 study testing LXH254, LTT462 and Trametinib in people with Non-Small Cell Lung Cancer and Melanoma, run by Novartis Pharmaceuticals at 32 sites in 11 countries.
Trial summary
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, 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
- 241 participants
- Where
- 32 sitesin 11 countries
- Study dates
- 24 Feb 2017to 24 Apr 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have advanced or metastatic NSCLC or cutaneous melanoma
- Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (cutaneous melanoma) in tumor tissue
- All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
- ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
Who cannot join
- -Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. (Patients with KRAS mutant NSCLC with prior G12C inhibitor treatments are also excluded in the LXH254+trametinib expansion part). BRAF mutant patients group: Prior treatment with any EGFR, ALK, ROS1, KRAS, RAF (both BRAFV600 selective and pan-RAF), MEK1/2 and/or ERK1/2 inhibitors (for patients with BRAF V600 mutant NSCLC, prior treatments with BRAF and MEK1/2 inhibitors are allowed).
- Patients who have received more than 3 lines of anti-cancer therapy are excluded.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- 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.
- Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
- Patients with Gilbert's syndrome or other heritable diseases of bile processing.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
32 sites in 11 countries.
32 sites in 11 countries
United States6 sites
Massachusetts General Hospital SC
Boston, Massachusetts, 02114
Uni of TX MD Anderson Cancer Cntr
Houston, Texas, 77030
Sarah Cannon Research Institute Tennessee Oncology
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Ctr .
New York, New York, 10065
University of California San Diego .
San Diego, California, 92103
UCSF Medical Center
San Francisco, California, 94143
Spain6 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Barcelona, Catalonia, 08036
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
Seville, Andalusia, 41013
Novartis Investigative Site
Valencia, Valencia, 46010
Italy5 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Rozzano, MI, 20089
Novartis Investigative Site
Verona, VR, 37126
Germany4 sites
Novartis Investigative Site
Cologne, 50937
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Frankfurt, 60590
France3 sites
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Villejuif, 94800
Australia2 sites
Novartis Investigative Site
Melbourne, Victoria, 3000
Novartis Investigative Site
Westmead, New South Wales, 2145
South Korea2 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 06351
About this study
Official title: A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.
- Conditions
- Non-Small Cell Lung Cancer, Melanoma
- Being tested
- LXH254, LTT462, Trametinib, Ribociclib
- Keywords
- NSCLC, Melanoma, NRAS, KRAS, BRAF, LXH254, LTT462, Trametinib, Ribocliclib, Non-small cell lung carcinoma (NSCLC), treatment of lung cancer after first metastasis, lung cancer, lung adenocarcinoma, Large-cell lung carcinoma, Non small cell lung carcinoma, Non small cell lung cancer, Large cell lung carcinoma, Large cell lung cancer, squamous cell lung carcinoma
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Melanoma, Lung Neoplasms, Adenocarcinoma of Lung
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: LXH254; Drug: Trametinib |
| LXH254+Ribociclib | Experimental | Not described Receives: Drug: LXH254; Drug: Ribociclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
Measured: up to 5 years
Dose limiting toxicities (DLTs) (dose escalation only)
Measured: up to 3 years
Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
Measured: up to 5 years
Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity
Measured: Up to 5 years
Secondary outcomes (12)
Overall Response Rate (ORR)
Measured: Up to 5 years
Duration of response (DOR)
Measured: Up to 5 years
Disease Control Rate (DCR)
Measured: Up to 5 years
Progression Free Survival (PFS)
Measured: Up to 5 years
Overall Survival (OS) - (dose expansion part only)
Measured: Up to 5 years
Derived PK parameter (Cmax) for LXH254 & LTT462:
Measured: Up to 5 years
Derived PK parameter (AUC) for LXH254 & LTT462
Measured: Up to 5 years
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples
Measured: up to 5 years
Derived PK parameter (Cmax) for LXH254 & trametinib
Measured: up to 5 years
Derived PK parameter (AUC) for LXH254 & trametinib
Measured: Up to 5 years
Derived PK parameter (Cmax) for LXH254 & ribociclib
Measured: Up to 5 years
Derived PK parameter (AUC) for LXH254 & ribociclib
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2016 (estimated)
- Study start24 Feb 2017
- Primary completion24 Apr 2024
- Study completion24 Apr 2024
Why it stopped: Business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 241 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02974725
- Sponsor's protocol ID
- CLXH254X2102
- Other IDs
- 2016-004293-18, 2016
- Status last verified
- Apr 2025
- First submitted
- 23 Nov 2016
- Last updated
- 13 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist RS, Sun JM, Min Kim T, Reguart N, Sanmamed MF, Felip E, Garrido P, Santoro A, Bootle D, Couillebault XM, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer. 2024 Nov;197:107964. doi: 10.1016/j.lungcan.2024.107964. Epub 2024 Sep 26.
PubMed 39383771de Braud F, Dooms C, Heist RS, Lebbe C, Wermke M, Gazzah A, Schadendorf D, Rutkowski P, Wolf J, Ascierto PA, Gil-Bazo I, Kato S, Wolodarski M, McKean M, Munoz Couselo E, Sebastian M, Santoro A, Cooke V, Manganelli L, Wan K, Gaur A, Kim J, Caponigro G, Couillebault XM, Evans H, Campbell CD, Basu S, Moschetta M, Daud A. Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study. J Clin Oncol. 2023 May 10;41(14):2651-2660. doi: 10.1200/JCO.22.02018. Epub 2023 Mar 22.
PubMed 36947734
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Open-label, Multicenter Study of Oral LXH254-centric Combinations in Adult Patients With Advanced or Metastatic KRAS or BRAF Mutant Non-Small Cell Lung Cancer or NRAS Mutant Melanoma
- ClinicalTrials.gov ID
- NCT02974725
- Acronym / sponsor ID
- CLXH254X2102
- Conditions
- Non-Small Cell Lung Cancer, Melanoma
- Keywords
- NSCLC, Melanoma, NRAS, KRAS, BRAF, LXH254, LTT462, Trametinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons
- Enrolment
- 241 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 24 Feb 2017 (actual)
- Primary completion
- 24 Apr 2024 (actual)
- Study completion
- 24 Apr 2024 (actual)
- First posted
- 28 Nov 2016 (estimated)
- 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.
To characterize safety and tolerability and identify a recommended dose and regimen for the LXH254 in combination with LTT462 or trametinib or ribociclib.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| LXH254+LTT462 | Experimental | Drug: LXH254, Drug: LTT462 |
| LXH254+Trametinib | Experimental | Drug: LXH254, Drug: Trametinib |
| LXH254+Ribociclib | Experimental | Drug: LXH254, Drug: Ribociclib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients must have advanced or metastatic NSCLC or cutaneous melanoma
- Presence of KRAS or BRAF mutation (NSCLC) or NRAS mutation (cutaneous melanoma) in tumor tissue
- All patients participating in this clinical trial must have progressed following standard therapy or, in the opinion of the Investigator, no effective standard therapy exists, is tolerated, appropriate or is considered equivalent to study treatment.
- ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
Key exclusion criteria (7 listed)
- -Dose expansion - KRAS or NRAS mutant patients groups: Prior treatment with a RAFi (including any BRAFi and pan-RAFi), MEKi and/or ERKi. (Patients with KRAS mutant NSCLC with prior G12C inhibitor treatments are also excluded in the LXH254+trametinib expansion part). BRAF mutant patients group: Prior treatment with any EGFR, ALK, ROS1, KRAS, RAF (both BRAFV600 selective and pan-RAF), MEK1/2 and/or ERK1/2 inhibitors (for patients with BRAF V600 mutant NSCLC, prior treatments with BRAF and MEK1/2 inhibitors are allowed).
- Patients who have received more than 3 lines of anti-cancer therapy are excluded.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- 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.
- Patients receiving proton pump inhibitors (PPI) which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
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, LXH254+Ribociclib, LXH254+Trametinib |
| 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
Number of participants with Adverse Events (AEs) as a measure of safety and tolerability
Time frame: up to 5 years
Dose limiting toxicities (DLTs) (dose escalation only)
Time frame: up to 3 years
Tolerability measured by the number of subjects who have interruptions/reductions of study treatment and reason for interruptions/reductions
Time frame: up to 5 years
Tolerability measured by the dose intensity of study drug, Relative Dose intensity for subjects with non-zero duration of exposure is computed as the ratio of dose intensity and planned dose intentity
Time frame: Up to 5 years
12 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to 5 years
Duration of response (DOR)
Time frame: Up to 5 years
Disease Control Rate (DCR)
Time frame: Up to 5 years
Progression Free Survival (PFS)
Time frame: Up to 5 years
Overall Survival (OS) - (dose expansion part only)
Time frame: Up to 5 years
Derived PK parameter (Cmax) for LXH254 & LTT462:
Time frame: Up to 5 years
Derived PK parameter (AUC) for LXH254 & LTT462
Time frame: Up to 5 years
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor samples
Time frame: up to 5 years
Derived PK parameter (Cmax) for LXH254 & trametinib
Time frame: up to 5 years
Derived PK parameter (AUC) for LXH254 & trametinib
Time frame: Up to 5 years
Derived PK parameter (Cmax) for LXH254 & ribociclib
Time frame: Up to 5 years
Derived PK parameter (AUC) for LXH254 & ribociclib
Time frame: Up to 5 years
Results and safety
The study was stopped early (reason given: Business reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2025.
- Derived from this study: PubMed 39383771Planchard D, Wolf J, Solomon B, Sebastian M, Wermke M, Heist RS, Sun JM, Min Kim T, Reguart N, Sanmamed MF, Felip E, Garrido P, Santoro A, Bootle D, Couillebault XM, Gaur A, Mueller C, Poggio T, Yang J, Moschetta M, Dooms C. A phase Ib study of the combination of naporafenib with rineterkib or trametinib in patients with advanced and metastatic KRAS- or BRAF-mutant non-small cell lung cancer. Lung Cancer. 2024 Nov;197:107964. doi: 10.1016/j.lungcan.2024.107964. Epub 2024 Sep 26.
- Derived from this study: PubMed 36947734de Braud F, Dooms C, Heist RS, Lebbe C, Wermke M, Gazzah A, Schadendorf D, Rutkowski P, Wolf J, Ascierto PA, Gil-Bazo I, Kato S, Wolodarski M, McKean M, Munoz Couselo E, Sebastian M, Santoro A, Cooke V, Manganelli L, Wan K, Gaur A, Kim J, Caponigro G, Couillebault XM, Evans H, Campbell CD, Basu S, Moschetta M, Daud A. Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study. J Clin Oncol. 2023 May 10;41(14):2651-2660. doi: 10.1200/JCO.22.02018. Epub 2023 Mar 22.
- Study ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
32 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LXH254, LTT462 and Trametinib in people with Non-Small Cell Lung Cancer and Melanoma, run by Novartis Pharmaceuticals at 32 sites in 11 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 4 inclusion and 7 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: stopped early, as of the sponsor's last update on 13 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 32 sites in United States, Spain, Italy, Germany, France and 6 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business reasons). Results are not available in the source record.
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?
Number of participants with Adverse Events (AEs) as a measure of safety and tolerability (time frame: up to 5 years). The study lists 4 primary outcomes in all. 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 NCT02974725, which also lists 2 linked publications.
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 13 Apr 2025.