previously treated unresectable or metastatic BRAFV600 or NRAS mutant melanoma MedDRA version: 21.1 Level: PT Classification code 10027480 Term: Metastatic malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027150 Term: Melanoma malignant System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female must be = 18 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. -Prior checkpoint inhibitor therapy in the unresectable or metastatic setting is not required for participants who have progressed on or within 6 months of adjuvant therapy with a checkpoint inhibitor. -Prior therapy with T-VEC (talimogene laherparepvec) is allowed and will not be counted as a prior line of systematic therapy -A maximum of two prior lines of systemic CPI-containing immunotherapy for unresectable or metastatic melanoma are allowed. Additional agents administered with a 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 >6 months. Participants with BRAFV600 mutant disease: -Participants must have received prior systemic therapy for unresectable or metastatic melanoma with a checkpoint inhibitor (CPI), either an anti-PD-1/anti-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. -Prior checkpoint inhibitor therapy in the unresectable or metastatic setting is not required for participants who have progressed on or within 6 months of adjuvant checkpoint inhibitors. -Prior therapy with T-VEC (talimogene laherparepvec) is allowed and will not be counted as a prior line of systematic therapy -A maximum of two prior lines of CPI-containing systemic 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 -If a participant discontinued targeted therapy for reasons other than disease progression, a switch to another targeted therapy regimen is allowed -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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 265 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
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). - 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. - 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 inclusion/exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the anti-tumor efficacy of LXH254 in combination with novel agents including LTT462, trametinib, ribociclib in participants with previously treated unresectable or metastatic, BRAFV600 or NRAS mutant melanoma as measured by objective response rate.;Secondary Objective: - To characterize the safety and tolerability of each combination arm - To further evaluate the efficacy of each combination arm - To evaluate the OS of each combination arm - To characterize the pharmacokinetics of each combination regimen;Primary end point(s): Confirmed objective response rate (ORR) using RECIST v1.1, per local assessment;Timepoint(s) of evaluation of this end point: Patient has at least 8 months or has progressed, died, discontinued study or started new anti-neoplastic therapy earlier. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To characterize the safety and tolerability of each combination arm - incidence and severity of adverse events and serious adverse events - dose interruptions, reductions, and permanent discontinuations To further evaluate the efficacy of each combination arm - Duration of response, progression-free survival, and disease control rate using RECIST 1.1 - Duration of response, progression-free survival, disease control rate, and objective response rate using RECIST 1.1 for all participants for the combination arms that moved to expansion To evaluate the overall survival of each combination arm To characterize the pharmacokinetics of each combination arm - Serum/plasma concentration, pharmacokinetic parameters of each combination;Timepoint(s) of evaluation of this end point: The first review for safety only will occur when the first 15 participants in each treatment combination arm (45 participants in each mutation group) have been enrolled and received 2 cycles of treatment or discontinued therapy. The second review will occur with the first interim analysis, when the first 30 patients have been enrolled and followed for 8 months or discontinued therapy. | — |
Countries
Argentina, Australia, Austria, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Norway, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactMedisinsk informasjon
Novartis Norge AS
Outcome results
None listed