Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Incidence of dose limiting toxicities (DLTs) experienced during Cycle 1 |
|
At the end of Cycle 1. Each cycle is 28 days. |
|
Secondary |
Incidence, nature and severity of treatment emergent adverse events (TEAEs) |
Incidence, nature and severity of treatment emergent adverse events (TEAEs) graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03, TEAEs leading to dose interruption, reduction and discontinuation, treatment-emergent serious adverse events (SAEs) and deaths will be reported. |
Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months. Each cycle is 28 days. |
|
Secondary |
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of blood hematology parameters |
Clinically notable shift from baseline in blood hematology parameters data [Hemoglobin (Low/High); Leukocytes (Low/ High); Neutrophils (Low); Platelets (Low/High); Lymphocytes (Low/High)] will be graded using NCI CTCAE Version 4.03. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above. Number of participants with at least one clinically notable shift during study will be reported. |
Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days. |
|
Secondary |
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of blood clinical chemistry parameters |
Clinically notable shift from baseline in blood clinical chemistry parameter values [Phosphate (Low); Alanine Aminotransferase (High); Albumin (Low); Alkaline Phosphatase (High); Aspartate Aminotransferase (High); Bilirubin (High); Calcium Corrected (Low/High); Creatinine (High); Glucose (Low/High); Magnesium (Low/High); Potassium (Low/High); Sodium (Low/High)] will be graded using NCI-CTCAE, Version 4.03. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above. Number of participants with at least one clinically notable shift during study will be reported. |
Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days. |
|
Secondary |
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of coagulation parameters |
Clinically notable shift from baseline in coagulation parameters parameter values [activated partial thromboplastin time (seconds), international normalized ratio (INR) or prothrombin time (seconds)] will be graded using NCI-CTCAE, Version 4.03. Number of participants with abnormal levels or notable shift during study will be reported. |
Screening (Days -28 to -1), Cycle 1 Day 1 (if not done within 72 hours before the first dose), Cycle 1 Day 15, on Day 1 each subsequent cycle, end of treatment visit 30 day safety follow up visit, approximately up to 6 months. Each cycle is 28 days. |
|
Secondary |
Incidence of treatment emergent adverse events (TEAEs) related to notable change from baseline of dipstick urinalysis |
Quantitative assessment of appearance, color, specific gravity, blood, glucose, leukocytes, ketones, pH and protein at each visit and changes from baseline (for quantitative parameters) will be calculated and tabulated. Microscopy findings (normal/abnormal and clinical significance) will be recorded. Number of participants with abnormal/ clinical significant changes during study will be reported. |
Days -28 to -1,Cycle1 Day1 (if not done w/in 72 hours before first dose),Cycle1 Day15,on Day1 each subsequent cycle,end of treatment visit 30 day safety FU visit,approx. up to 6 months. Add'l urinalysis in Cycle 1 Days 8 and 22. Each cycle is 28 days. |
|
Secondary |
Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations. |
Clinically notable elevated values: Systolic blood pressure (BP): = 160 mmHg and an increase = 20 mmHg from baseline; Diastolic BP: = 100 mmHg and an increase = 15 mmHg from baseline; Heart rate : = 120 beats/min (bpm) with increase from baseline of = 15 bpm; Weight (kg) increase from baseline of = 10%; Body temperature(°C) = 37.5°C). Clinically notable low values: Systolic BP: = 90 mmHg with decrease from baseline of = 20 mmHg; Diastolic BP: = 50 mmHg with decrease from baseline of = 15 mmHg; Heart rate: = 50 bpm with decrease from baseline of = 15 bpm; Weight: = 20% decrease from baseline; Body temperature [°C]: = 36 °C. Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported. |
Screening (Days -28 to -1), Cycle 1 Days 1, 8, 15 and 22, Day 1 of each subsequent cycle, the end of treatment visit and the 30-day safety follow-up visit, approximately up to 6 months. Each cycle is 28 days. |
|
Secondary |
Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs) |
12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT [millisecond (ms)] and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms): increase from baseline > 30 ms; increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms. Heart rate (beats/min): increase from baseline > 25% to a value > 100 bpm, decrease from baseline > 25% and to a value < 50 bpm. Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported. |
Screening (Days -28 to -1), Cycle 1 Day 8, 15 and 22, Day 1 of each subsequent even cycle (Cycle 2, 4, 6, …) and the end of treatment visit, approximately up to 6 months. Each cycle is 28 days. |
|
Secondary |
Incidence of targeted treatment emergent adverse events (TEAEs) of special interest |
Adverse event of special interest (AESI) are as follows: acute renal failure, cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma, melanomas, palmar-plantar erythrodysaesthesia syndrome, photosensitivity, rash, severe cutaneous adverse reactions, facial paresis, tachycardia, haemorrhage, hepatic failure, liver function test abnormalities, myopathy and uveitis-type events. Number and percentage of participants with at least one event of any AESI and of each category of AESI will be reported in participants. |
Cycle 1 Day 1 through safety follow-up visit (30 days after end of treatment (EOT) visit or 7 days after end EOT visit/last dose if EOT not performed), approximately up to 6 months. |
|
Secondary |
Plasma pharmacokinetics (PK) of encorafenib: Area under the curve (AUC) after single and repeated administration of encorafenib |
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days. |
|
Secondary |
Plasma pharmacokinetics (PK) of encorafenib metabolite (LHY746): Area under the curve (AUC) after single and repeated administration of encorafenib |
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days. |
|
Secondary |
Plasma pharmacokinetics (PK) of encorafenib: Maximum concentration (Cmax) after single and repeated administration of encorafenib |
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days. |
|
Secondary |
Plasma pharmacokinetics (PK) of encorafenib metabolite (LHY746): Maximum concentration (Cmax) after single and repeated administration of encorafenib |
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days. |
|
Secondary |
Plasma pharmacokinetics (PK) of encorafenib: Minimum concentration (Cmin) after single and repeated administration of encorafenib |
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days. |
|
Secondary |
Plasma pharmacokinetics (PK) of encorafenib metabolite (LHY746): Minimum concentration (Cmin) after single and repeated administration of encorafenib |
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle is 28 days. |
|