A Phase II, Open-label Study to Assess the Safety and Efficacy of Oral MEK162 in Adults With Locally Advanced and Unresectable or Metastatic Malignant Cutaneous Melanoma, Harboring BRAFV600 or NRAS Mutations

简要总结

主要结局

次要结局

• Progression-Free Survival (PFS)(From date of randomization or date of start of treatment until date of first documentation of PD or date of death due to any cause or date of data censoring, whichever occurred first (maximum duration of up to 33 months))
• Overall Survival (OS)(From date of randomization or date of start of treatment to date of death due to any cause or date of censoring, whichever occurred first (maximum duration of up to 33 months))
• Duration of Response (DOR)(From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum duration of up to 33 months))
• Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Hematology)(Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately))
• Time to Response (TTR)(From the date of randomization or date of start of treatment to the first documentation of objective response (CR or PR) or data censoring date, whichever occurred first (maximum duration of up to 33 months))
• Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Chemistries)(Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately))
• Number of Participants With Markedly Abnormal Vital Sign Values: Sitting Pulse Rate(Baseline up to 30 days after last dose of study drug (up to maximum of 33 months))
• Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Fundoscopy(Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months))
• Number of Participants With Serious Adverse Reactions(Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately))
• Number of Participants With Shift From Baseline in Vital Signs Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Blood Pressure)(Baseline up to 30 days after last dose of study drug (up to maximum of 33 months))
• Number of Participants With Markedly Abnormal Vital Sign Values: Weight(Baseline up to 30 days after last dose of study drug (up to maximum of 33 months))
• Number of Participants With Grade 3 or 4 Treatment-Emergent Adverse Reactions Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.0(Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately))
• Number of Participants With Notable Electrocardiogram (ECG) Values(Baseline up to 30 days after last dose of study drug (up to maximum of 33 months))
• Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Slit Lamp Examination(Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months))
• Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Maximum Plasma Concentration (Cmax) of Binimetinib(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Trough Plasma Concentration (Ctrough) of Binimetinib(Pre-dose (0 hour) on Day 15 of Cycle 1)
• Apparent Total Body Clearance (CL/F) of Binimetinib(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib's Metabolite(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Maximum Plasma Concentration (Cmax) of Binimetinib's Metabolite(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib's Metabolite(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib's Metabolite(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib's Metabolite(Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1)
• Trough Plasma Concentration (Ctrough) of Binimetinib's Metabolite(Pre-dose (0 hour) on Day 15 of Cycle 1)
• Percent Change From Baseline in Histological Score (H-score) for Phosphorylated Extracellular Signal-Regulated Kinase (pERK) From Tumor Samples of Cytoplasmic and Nuclear Cellular Compartment(Baseline up to maximum duration of up to 33 months)
• Percent Change From Baseline in Delta CT Values for Dual Specificity Phosphatase 6 (DUSP6) Expression From Tumor Samples(Baseline up to maximum duration of up to 33 months)