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. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04417621 |
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Recruitment Status :
Active, not recruiting
First Posted : June 4, 2020
Last Update Posted : October 23, 2023
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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Brief Summary:
The primary purpose of this study is to evaluate the efficacy of LXH254 combinations in previously treated unresectable or metastatic melanoma
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Melanoma | Drug: LXH254 Drug: LTT462 Drug: Trametinib Drug: Ribociclib | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 134 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 26, 2024 |
| Estimated Study Completion Date : | April 26, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Melanoma
MedlinePlus related topics:
Melanoma
Drug Information
available for:
Trametinib
| 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. |
Primary Outcome Measures :
- Overall Response Rate [ Time Frame: 35 months ]Confirmed ORR using RECIST v1.1, per local assessment
Secondary Outcome Measures :
- 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
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| Ages Eligible for Study: | 12 Years to 120 Years (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
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
Locations
Show 35 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04417621 |
| Other Study ID Numbers: |
CLXH254C12201 2020-000873-26 ( EudraCT Number ) |
| First Posted: | June 4, 2020 Key Record Dates |
| Last Update Posted: | October 23, 2023 |
| Last Verified: | October 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | 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. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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LXH254 Melanoma NRAS BRAF |
LTT462 Trametinib Ribocliclib |
Additional relevant MeSH terms:
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Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Nevi and Melanomas Skin Neoplasms |
Neoplasms by Site Skin Diseases Trametinib Naporafenib Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |