To evaluate the best sequencing approach with the combination of target agents (LGX818 plus MEK162) and the combination of immunomodulatory antibodies (ipilimumab plus nivolumab) in patients with metastatic melanoma and BRAF V600 mutation.
Name: LGX818
Name: MEK162
Name: Nivolumab
Name: Ipilimumab
Description: OS is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive. OS data will be collected continuously while subjects are on study medication and every 3 months via in-person or phone contact after discontinuation of study medication
Measure: Overall Survival Time: Patients enrolled will receive study medication until disease progression, unaccettable toxicity, withdrawal of consent or death, whichever comes first, assested up to 24 monthDescription: PFS is defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Tumor responses will be assessed by the Investigator according to RECIST Criteria (version 1.1)
Measure: Total Progression free survival Time: Baseline (Day 1), every 6 weeks until second disease progression is documented (Approximately around 2 years)Description: Percentage of patients alive at 2 and 3 years will be reported using Wilson score intervals.
Measure: Percentage of patients alive at 2 and 3 years; Time: Time Frame: at 24^ and 36^ monthDescription: It will be calculated as the percentage of ITT population patients who have a CR o o PR before any evidence of progression (as defined by RECIST).
Measure: Best overall response rate (BORR); Time: Time Frame: up to 24 monthsDescription: It will be calculated as the percentage of ITT population patients who have a CR o o PR before any evidence of progression (as defined by RECIST).
Measure: Duration of response (DoR); Time: Time Frame: up to 24 monthsDescription: Safety and tolerability will be assessed in terms od AEs, laboratory data, ECG data, vitals signs and weight, which will be collected for all patients. AEs (both in terms od MedDRA preferred terms and CTCAE grade), laboratory data, ECG data, vital signs and weight will be listes individually by patient and summarized by treatment received. ECG changes will be summarized for each treatment group.
Measure: Toxicity of the investigational medicinal products (IMPs). Time: Time Frame: up to 24 monthsDescription: Changes from baseline in EQ-5D and QLQ-C30 total score will be summarized by means of descriptive statistical methods.
Measure: Quality of life and general health Time: Time Frame: up to 24 monthsDescription: 3 years PFS rate; calculated from the date of randomization;
Measure: 3 years PFS rate Time: Time Frame: up to 36 monthsAllocation: Randomized
Parallel Assignment
There are 2 SNPs
4. Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria; 5. Presence of BRAF V600E or V600K mutation in tumor tissue prior to enrollment; 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1; 7. Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. --- V600E ---
4. Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria; 5. Presence of BRAF V600E or V600K mutation in tumor tissue prior to enrollment; 6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1; 7. Tumor tissue from an unresectable or metastatic site of disease must be provided for biomarker analyses. --- V600E --- --- V600K ---