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Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma

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 : November 5, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

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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 16, 2020
Estimated Primary Completion Date : April 27, 2023
Estimated Study Completion Date : April 27, 2023

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 :
  1. Overall Response Rate [ Time Frame: 35 months ]
    Confirmed ORR using RECIST v1.1, per local assessment


Secondary Outcome Measures :
  1. Duration of Reposnse (DOR) [ Time Frame: 4 years ]
    Local and central assessment

  2. Progression Free Survival (PFS) [ Time Frame: 4 years ]
  3. Disease Control Rate (DCR) [ Time Frame: 3 years ]
    Using RECIST v1.1, per local and central assessment

  4. Overall Survival (OS) [ Time Frame: 4 years ]
  5. Derived PK parameter (Cmax) for LXH254 & LTT462 [ Time Frame: Up to 5 months ]
  6. Derived PK parameter (Cmax) for LXH254 & trametinib [ Time Frame: Up to 5 months ]
  7. Derived PK parameter (Cmax) for LXH254 & ribociclib [ Time Frame: Up to 5 months ]
  8. Derived PK parameter (AUC) for LXH254 & LTT462 [ Time Frame: Up to 5 months ]
  9. Derived PK parameter (AUC) for LXH254 & trametinib [ Time Frame: Up to 5 months ]
  10. Derived PK parameter (AUC) for LXH254 & ribociclib [ Time Frame: Up to 5 months ]
  11. 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

  12. Dose Interruptions [ Time Frame: 35 months ]
    Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions

  13. Dose reductions [ Time Frame: 35 months ]
    Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions



Information from the National Library of Medicine

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.


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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 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


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


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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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         
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         
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04417621    
Other Study ID Numbers: CLXH254C12201
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: November 5, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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
Trametinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action