Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT04417621
- Lead Sponsor
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 134
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.
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LXH254 + LTT462 LTT462 - LXH254 + ribociclib Ribociclib - LXH254 + trametinib Trametinib - LXH254 + LTT462 LXH254 -
- Primary Outcome Measures
Name Time Method Overall Response Rate 35 months Confirmed ORR using RECIST v1.1, per local assessment
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) 3 years Using RECIST v1.1, per local and central assessment
Overall Survival (OS) 4 years Derived PK parameter (Cmax) for LXH254 & trametinib Up to 5 months Derived PK parameter (AUC) for LXH254 & ribociclib Up to 5 months Progression Free Survival (PFS) 4 years Duration of Reposnse (DOR) 4 years Local and central assessment
Derived PK parameter (AUC) for LXH254 & LTT462 Up to 5 months Dose reductions 35 months Tolerability measured by the number of subjects who have reductions of study treatment and reason for reductions
Incidence of adverse events (AEs) and serious adverse events (SAEs) 35 months Number of participants with Adverse Events (AEs) and SAEs as a measure of safety and tolerability
Dose Interruptions 35 months Tolerability measured by the number of subjects who have interruptions of study treatment and reason for interruptions
Derived PK parameter (AUC) for LXH254 & trametinib Up to 5 months Derived PK parameter (Cmax) for LXH254 & LTT462 Up to 5 months Derived PK parameter (Cmax) for LXH254 & ribociclib Up to 5 months
Trial Locations
- Locations (12)
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
H Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Univ of TX MD Anderson Cancer Cntr
🇺🇸Houston, Texas, United States
Mayo Clinic Mayo Rochester
🇺🇸Rochester, Minnesota, United States
NYU Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
University of Pittsburgh Med Center
🇺🇸Pittsburgh, Pennsylvania, United States
Novartis Investigative Site
🇬🇧Manchester, United Kingdom