BRAF V600E Metastatic NSCLC, BRAF V600E Unresectable or Metastatic Melanoma, Melanoma
Conditions
Keywords
NSCLC, Melanoma, BRAF V600E mutation
Brief summary
This is a phase 1, multicenter, open-label, single-arm study to investigate the safety and tolerability of encorafenib 300 mg once daily (QD) monotherapy in adult Chinese participants with B-RAF Proto-oncogene, Serine/threonine Kinase V600E (BRAF V600E) mutant advanced solid tumors (unresectable metastatic melanoma or metastatic non-small cell lung cancer (NSCLC)), who are BRAF-inhibitor treatment-naïve and have failed the previous therapy(ies) in the metastatic setting or are not eligible to standard therapy. Participants will be eligible for the study based on identification of a BRAF V600E mutation in tumor tissue by a local National Medical Products Administration (NMPA) approved assay obtained prior to screening.
Interventions
DRUGEncorafenib
oral capsule
Sponsors
Pierre Fabre Medicament
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provide a signed and dated informed consent form (ICF). 2. Chinese male or female with age ≥18 years old at the time of the informed consent. 3. Documented histology- and/or cytology-confirmed metastatic melanoma or non-small cell lung cancer (NSCLC) (i.e. adenocarcinoma, large cell carcinoma, squamous cell carcinoma). 4. Presence of B-RAF Proto-oncogene, Serine/threonine Kinase V600E Mutant (BRAF V600E) mutation as determined by a local laboratory with a National Medical Products Administration (NMPA) approved BRAF test. 5. BRAF inhibitor treatment-naïve participants and having failed the previous therapy(ies) for metastatic disease or are not eligible to standard therapy. 6. At least one tumor lesion as per investigator assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, which has neither been irradiated nor biopsied during the screening period. The irradiated lesion is acceptable only if it is proven as disease progression deemed measurable prior to study. 7. Life expectancy ≥3 months. 8. Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1. 9. Adequate hematologic function at screening and baseline 10. Adequate hepatic function at screening and baseline 11. Adequate renal function at screening and baseline 12. Able to comply with the study protocol as per investigator assessment including oral drug intake, complying scheduled visits, treatment plan, laboratory tests and other study procedures. 13. Women are either postmenopausal for at least 1 year, or are surgically sterile for at least 6 weeks, or women of childbearing potential (WOCBP) must agree to take appropriate precautions to avoid pregnancy. 14. Men must agree not to father child until 90 days after the last dose of study treatment.
Exclusion criteria
1. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to encorafenib, or its excipients. 2. For metastatic NSCLC: documented anaplastic lymphoma kinase (ALK) fusion oncogene, ROS1 (c-ros oncogene 1) rearrangement or epidermal growth factor receptor (EGFR) sensitizing or driver mutation. 3. Receipt of anticancer medications or investigational drugs within intervals before the first administration of study treatment. 4. Symptomatic brain metastasis. 5. Leptomeningeal disease. 6. Participant has not recovered to ≤Grade 1 from toxic effects of prior therapy and/or complications from prior surgical treatment before starting study treatment. 7. Current use of prohibited medication ≤1 week prior to start of the study treatment and/or concomitantly. 8. Impairment of gastrointestinal function or disease which may significantly alter the absorption of oral study treatment. 9. Impaired cardiovascular function or clinically significant cardiovascular diseases. 10. Participants with active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) or any other severe viral active infection (e.g. severe acute respiratory syndrome coronavirus 2 \[SARS-CoV-2\] infection). 11. Evidence of active, non-infectious pneumonitis, history of interstitial lung disease that required oral or intravenous glucocorticoid steroids for management. 12. Known history of a positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Testing for HIV must be performed at sites where mandated locally. 13. Participants who have had major surgery (e.g. inpatient procedure with regional or general anesthesia) within 6 weeks prior to start of study treatment. 14. Previous or concurrent malignancy within 2 years of study entry. Except: 1. Bowen's disease. 2. Cured basal cell or squamous cell skin cancer. 3. Gleason 6 prostate cancer. 4. Treated in-situ carcinoma of cervix. 15. Participant's conditions that contraindicates the use of study treatment and may affect interpretation of results or that may render the participant at high risk from treatment complications. 16. Pregnant (confirmed by positive serum beta-human Chorionic Gonadotropin (ß-HCG) test), lactating or breast-feeding women. 17. Is a family member of the Investigator or any associate, colleague, and employee assisting in the conduct of the study (secretary, nurse, technician). 18. Is in a position likely to represent a conflict of interest.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLTs) Experienced During Cycle 1 | At the end of Cycle 1. Each cycle was 28 days. | The primary endpoint was the number of patients experiencing dose limiting toxicity (DLT) occurring within the first 28 days of study treatment (Cycle 1). A DLT was defined as any adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies resulting in the inability to tolerate at least 75% dose intensity \[(administered dose in mg/planned dose in mg) × 100\] that satisfied at least one of the prespecified criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | 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 was 28 days. | Clinically notable shift from baseline in blood hematology parameters data \[Hemoglobin (Low/High); Leukocytes (Low/ High); Neutrophils (Low); Platelets (Low); Lymphocytes (Low/High)\] was graded using NCI CTCAE Version 4.03. Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above. The number of participants with clinically notable shift from baseline is presented. |
| Notable Change From Baseline of Blood Clinical Chemistry Parameters | 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 was 28 days. | Clinically notable shift from baseline in blood clinical chemistry parameter values \[Phosphate (Low); Alanine Aminotransferase (High); Albumin (Low); Alkaline Phosphatase (High); Aspartate Aminotransferase (High); Bilirubin (High); Calcium Corrected (Low/High); Creatinine (High); Glucose (Low/High); Magnesium (Low/High); Potassium (Low/High); Sodium (Low/High); amylase (high); Gamma Glutamyl Transferase (High); Lipase (High) and Urate (High)\] was graded using NCI-CTCAE, Version 4.03. Clinically notable shift was 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 was reported. |
| Notable Change From Baseline of Coagulation Parameters | 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 was 28 days. | The maximum post baseline values of coagulation parameters \[activated partial thromboplastin time (seconds) and prothtombin international normalized ratio (INR)\]. It was graded using NCI-CTCAE, Version 4.03. The number of participants is presented with their worst NCI-CTCAE grade post-baseline. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting ageappropriate instrumental ADL\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. |
| Notable Change From Baseline of Dipstick Urinalysis | Days -28 to -1, Cycle1 Day1 (if not within 72 hours before first dose),Cycle1 Day15,on Day1 each subsequent cycle,end of treatment visit 30 day safety follow up visit, up to 6 months. Additional urinalysis in Cycle 1 Days 8 and 22. Each cycle was 28 days. | The appearance of dipstick, at each visit by participant is presented. |
| Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | 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 was 28 days. | Clinically notable elevated values: Systolic blood pressure (SBP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic blood pressure (DBP): ≥ 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 blood pressure (SBP): ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic blood pressure (DBP) : ≤ 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 clinically notable abnormalities in vital signs was reported. |
| Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | Screening (Days -28 to -1), Cycle 1 Day 8, 15 and 22, Day 1 of each subsequent even cycle, and the end of treatment visit, approximately up to 6 months. Each cycle was 28 days. | 12-lead ECGs were 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 clinically notable values was reported. |
| Occurrence of Targeted Treatment Emergent Adverse Events (TEAEs) of Special Interest | 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. | Adverse event of special interest (AESI) were as follows: Cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma, melanomas, facial paresis, uveitis-type events, QT prolongation, non-cutaneous malignancies with RAS mutation. Number of participants with at least one event of any AESI is presented. |
| 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 was 28 days. | All enrolled participants (n=3) received at least two doses of Encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Area under the curve of Encorafenib was assessed after single and repeated administrations. AUC0-tlast = area under the concentration curve from time 0 to time of last measurable concentration |
| Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days. | All enrolled participants (n=3) received at least two doses of Encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Area under the curve of Encorafenib metabolite (LHY746) was assessed after single and repeated administrations. AUC0-tlast = area under the concentration curve from time 0 to time of last measurable concentration |
| Occurrence of Treatment Emergent Adverse Events (TEAEs) | 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 was 28 days. | The occurrences 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 were reported. The number of events occurring in the three participants is presented. |
| 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 was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Maximum Concentration of encorafenib metabolite (LHY746) was assessed after single and repeated administrations. |
| 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 was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Minimum concentration of encorafenib was assessed after single and repeated administrations. |
| 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 was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Minimum concentration of encorafenib metabolite (LHY746) was assessed after single and repeated administrations. |
| Plasma Pharmacokinetics (PK) of Encorafenib: Time Taken to Reach Maximum Concentration (Tmax) 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 was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The time taken to reach maximum concentration of Encorafenib was assessed after single and repeated administrations. |
| Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The time taken to reach maximum concentration of Encorafenib Metabolite (LHY746) was assessed after single and repeated administrations. |
| Plasma Pharmacokinetics (PK) of Encorafenib: ARAUC After Single and Repeated Administration of Encorafenib | at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days. | All enrolled participants (n=3) received at least two doses of Encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The ARAUC of Encorafenib was assessed after single and repeated administrations. ARAUC = Observed accumulation ratio based on AUC0-6 |
| Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): ARAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The ARAUC of encorafenib metabolite (LHY746) was assessed after single and repeated administrations. ARAUC = Observed accumulation ratio based on AUC0-6 |
| Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): MRAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The MRAUC of encorafenib metabolite (LHY746) was assessed after single and repeated administrations. MRAUC = Metabolite Parent ratio based on AUC0-6 |
| 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 was 28 days. | All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Maximum Concentration of encorafenib was assessed after single and repeated administrations. |
Countries
China
Participant flow
Pre-assignment details
This study had no fixed duration and participants were expected to be treated until progressive disease. The three enrolled participants were to be treated until death, disease progression.
Participants by arm
| Arm | Count |
|---|---|
| Encorafenib Encorafenib hard capsule was orally administered. A fixed-flat dose of 300 mg (4 x 75 mg) Per Oral (PO) encorafenib was administered once-daily (QD). | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Progressive disease | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Encorafenib |
|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 0 |
| Body Mass Index | 24.773 kilograms/meters squared STANDARD_DEVIATION 2.437 |
| BRAF V600E Mutation Result (Local) Negative | 0 Participants |
| BRAF V600E Mutation Result (Local) Positive | 3 Participants |
| Diagnosis at study entry Metastatic Melanoma | 0 Participants |
| Diagnosis at study entry Metastatic NSCLC | 3 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Performance Status 0 | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Performance Status 1 | 3 Participants |
| Height | 163.07 centimeters STANDARD_DEVIATION 5.01 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 3 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
| Smoking history Never smoked | 0 Participants |
| Smoking history Smoker | 0 Participants |
| Smoking history Stopped smoking less than 10 years ago | 3 Participants |
| Smoking history Stopped smoking more than or equal to 10 years ago | 0 Participants |
| Weight | 65.73 kilograms STANDARD_DEVIATION 4.87 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
Dose Limiting Toxicities (DLTs) Experienced During Cycle 1
The primary endpoint was the number of patients experiencing dose limiting toxicity (DLT) occurring within the first 28 days of study treatment (Cycle 1). A DLT was defined as any adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, intercurrent illness or concomitant medications/therapies resulting in the inability to tolerate at least 75% dose intensity \[(administered dose in mg/planned dose in mg) × 100\] that satisfied at least one of the prespecified criteria.
Time frame: At the end of Cycle 1. Each cycle was 28 days.
Population: Dose-determining Set. The Dose-determining set consisted of all evaluable participants from the Safety Analysis Set who either achieved the minimum exposure requirement (i.e., encorafenib dose intensity of 75% in Cycle 1) and had sufficient safety evaluations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Encorafenib | Dose Limiting Toxicities (DLTs) Experienced During Cycle 1 | 0 participants |
Secondary
Notable Change From Baseline of Blood Clinical Chemistry Parameters
Clinically notable shift from baseline in blood clinical chemistry parameter values \[Phosphate (Low); Alanine Aminotransferase (High); Albumin (Low); Alkaline Phosphatase (High); Aspartate Aminotransferase (High); Bilirubin (High); Calcium Corrected (Low/High); Creatinine (High); Glucose (Low/High); Magnesium (Low/High); Potassium (Low/High); Sodium (Low/High); amylase (high); Gamma Glutamyl Transferase (High); Lipase (High) and Urate (High)\] was graded using NCI-CTCAE, Version 4.03. Clinically notable shift was 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 was reported.
Time frame: 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 was 28 days.
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Albumin (g/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Alkaline Phosphatase (IU/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Alanine Aminotransferase (IU/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Aspartate Aminotransferase (IU/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Bilirubin (umol/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Calcium Corrected (mmol/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Calcium Corrected (mmol/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Creatine Kinase (IU/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Creatinine (umol/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Gamma Glutamyl Transferase (IU/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Glucose (mmol/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Glucose (mmol/L) (High) | 1 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Lipase (IU/L) (High) | 1 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Amylase (IU/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Magnesium (mmol/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Magnesium (mmol/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Phosphate (mmol/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Potassium (mmol/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Potassium (mmol/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Sodium (mmol/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Sodium (mmol/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Clinical Chemistry Parameters | Urate (umol/L) (High) | 0 Participants |
Secondary
Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes.
Clinically notable shift from baseline in blood hematology parameters data \[Hemoglobin (Low/High); Leukocytes (Low/ High); Neutrophils (Low); Platelets (Low); Lymphocytes (Low/High)\] was graded using NCI CTCAE Version 4.03. Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above. The number of participants with clinically notable shift from baseline is presented.
Time frame: 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 was 28 days.
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Hemoglobin (g/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Hemoglobin (g/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Platelets (10^9/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Leukocytes (10^9/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Leukocytes (10^9/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Lymphocytes (10^9/L) (Low) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Lymphocytes (10^9/L) (High) | 0 Participants |
| Encorafenib | Notable Change From Baseline of Blood Hematology Parameters: Hemoglobin, Leukocytes, Neutrophils, Platelets, Lymphocytes. | Neutrophils (10^9/L) (Low) | 0 Participants |
Secondary
Notable Change From Baseline of Coagulation Parameters
The maximum post baseline values of coagulation parameters \[activated partial thromboplastin time (seconds) and prothtombin international normalized ratio (INR)\]. It was graded using NCI-CTCAE, Version 4.03. The number of participants is presented with their worst NCI-CTCAE grade post-baseline. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting ageappropriate instrumental ADL\*. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL\*\*. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time frame: 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 was 28 days.
Population: Safety Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Activated Partial Thromboplastin Time (sec) | Grade 0 | 3 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Activated Partial Thromboplastin Time (sec) | Grade 1 | 0 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Activated Partial Thromboplastin Time (sec) | Grade 2 | 0 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Activated Partial Thromboplastin Time (sec) | Grade 3 | 0 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Activated Partial Thromboplastin Time (sec) | Grade 4 | 0 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Prothrombin International Normalized Ratio (RATIO) | Grade 0 | 2 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Prothrombin International Normalized Ratio (RATIO) | Grade 1 | 1 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Prothrombin International Normalized Ratio (RATIO) | Grade 2 | 0 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Prothrombin International Normalized Ratio (RATIO) | Grade 3 | 0 Participants |
| Encorafenib | Notable Change From Baseline of Coagulation Parameters | Prothrombin International Normalized Ratio (RATIO) | Grade 4 | 0 Participants |
Secondary
Notable Change From Baseline of Dipstick Urinalysis
The appearance of dipstick, at each visit by participant is presented.
Time frame: Days -28 to -1, Cycle1 Day1 (if not within 72 hours before first dose),Cycle1 Day15,on Day1 each subsequent cycle,end of treatment visit 30 day safety follow up visit, up to 6 months. Additional urinalysis in Cycle 1 Days 8 and 22. Each cycle was 28 days.
Population: Safety Analysis Set
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Baseline | Clear | 3 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Baseline | Cloudy | 0 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 1 Day 8 | Clear | 3 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 1 Day 8 | Cloudy | 0 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 1 Day 15 | Clear | 3 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 1 Day 15 | Cloudy | 0 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 1 Day 22 | Clear | 3 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 1 Day 22 | Cloudy | 0 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 2 Day 1 | Clear | 3 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 2 Day 1 | Cloudy | 0 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 3 Day 1 | Clear | 2 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 3 Day 1 | Cloudy | 1 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 4 Day 1 | Clear | 3 Participants |
| Encorafenib | Notable Change From Baseline of Dipstick Urinalysis | Cycle 4 Day 1 | Cloudy | 0 Participants |
Secondary
Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs)
12-lead ECGs were 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 clinically notable values was reported.
Time frame: Screening (Days -28 to -1), Cycle 1 Day 8, 15 and 22, Day 1 of each subsequent even cycle, and the end of treatment visit, approximately up to 6 months. Each cycle was 28 days.
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QT Interval : Increase from baseline > 30 ms | 1 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QT Interval : Increase from baseline > 60 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QT Interval : New > 450 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QT Interval : New > 480 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QT Interval : New > 500 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QTcF Interval : Increase from baseline > 30 ms | 1 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QTcF Interval : Increase from baseline > 60 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QTcF Interval : New > 450 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QTcF Interval : New > 480 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | QTcF Interval : New > 500 ms | 0 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | Heart rate : Increase from baseline > 25% to a value > 100 bpm | 1 Participants |
| Encorafenib | Notable or Abnormal Changes From Baseline of 12-lead Electrocardiograms (ECGs) | Heart rate : Decrease from baseline > 25% and to a value < 50 bpm | 0 Participants |
Secondary
Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations.
Clinically notable elevated values: Systolic blood pressure (SBP): ≥ 160 mmHg and an increase ≥ 20 mmHg from baseline; Diastolic blood pressure (DBP): ≥ 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 blood pressure (SBP): ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; Diastolic blood pressure (DBP) : ≤ 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 clinically notable abnormalities in vital signs was reported.
Time frame: 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 was 28 days.
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable elevated value: SBP : ≥160 mmHg and an increase ≥ 20 mmHg from baseline | 1 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable elevated values: DBP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline | 1 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable elevated values: Pulse rate: ≥ 120 bpm with increase from baseline of ≥15 bpm | 1 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable elevated values: Weight: increase from baseline of ≥ 10% | 0 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable elevated values: Body temperature [C]: ≥ 37.5 C | 0 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable low values: SBP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg | 0 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable low values: DBP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg | 0 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable low values: Pulse rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm | 0 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable low values: Weight: ≥ 20% decrease from baseline | 0 Participants |
| Encorafenib | Notable or Abnormal Changes in Vital Signs From Baseline of Vital Sign Examinations. | Clinically notable low values: Body temperature [C]: ≤ 36 C | 1 Participants |
Secondary
Occurrence of Targeted Treatment Emergent Adverse Events (TEAEs) of Special Interest
Adverse event of special interest (AESI) were as follows: Cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma, melanomas, facial paresis, uveitis-type events, QT prolongation, non-cutaneous malignancies with RAS mutation. Number of participants with at least one event of any AESI is presented.
Time frame: 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.
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Encorafenib | Occurrence of Targeted Treatment Emergent Adverse Events (TEAEs) of Special Interest | 0 participants |
Secondary
Occurrence of Treatment Emergent Adverse Events (TEAEs)
The occurrences 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 were reported. The number of events occurring in the three participants is presented.
Time frame: 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 was 28 days.
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs Overall | 53 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs Related | 17 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs Grade 3+ | 3 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs Related Grade 3+ | 2 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | Serious TEAE Grade 3+ | 2 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | Serious TEAE Overall | 3 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | Serious TEAE Related | 2 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | Serious TEAE Related Grade 3+ | 1 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | Serious TEAE Leading to Death | 0 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAE by severity grade Grade 1 | 37 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAE by severity grade Grade 2 | 13 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAE by severity grade Grade 3 | 3 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAE leading to discontinuation of encorafenib regardless of causality Overall | 0 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib dose modification (interruption or reduction) Overall | 6 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib dose modification (interruption or reduction) Related | 4 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib dose modification (interruption or reduction) Grade 3+ | 1 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib dose modification (interruption or reduction) Related Grade 3+ | 1 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib drug interruption Overall | 5 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib drug interruption Related | 4 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib drug interruption Grade 3+ | 1 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib drug interruption Related Grade 3+ | 1 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAEs leading to encorafenib dose reduction Overall | 1 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAE action taken with encorafenib Dose not Change | 47 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAE action taken with encorafenib Dose Reduced | 1 events |
| Encorafenib | Occurrence of Treatment Emergent Adverse Events (TEAEs) | TEAE action taken with encorafenib Drug Interrupted | 5 events |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib: ARAUC After Single and Repeated Administration of Encorafenib
All enrolled participants (n=3) received at least two doses of Encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The ARAUC of Encorafenib was assessed after single and repeated administrations. ARAUC = Observed accumulation ratio based on AUC0-6
Time frame: at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetics Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: ARAUC After Single and Repeated Administration of Encorafenib | 0.440 ratio | Geometric Coefficient of Variation 40.2 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib: Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib
All enrolled participants (n=3) received at least two doses of Encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Area under the curve of Encorafenib was assessed after single and repeated administrations. AUC0-tlast = area under the concentration curve from time 0 to time of last measurable concentration
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetics Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib | Cycle 1 Day 1 AUC0-tlast | 21800 h*ng/mL | Standard Deviation 4620 |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib | Cycle 2 Day 1 AUC0-tlast | 9550 h*ng/mL | Standard Deviation 1750 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib: Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Maximum Concentration of encorafenib was assessed after single and repeated administrations.
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib | Cycle 1 Day 1 Cmax | 5590 (ng/mL) | Standard Deviation 351 |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib | Cycle 2 Day 1 Cmax | 3630 (ng/mL) | Standard Deviation 1750 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): ARAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746)
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The ARAUC of encorafenib metabolite (LHY746) was assessed after single and repeated administrations. ARAUC = Observed accumulation ratio based on AUC0-6
Time frame: at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetics Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): ARAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | 2.27 ratio | Geometric Coefficient of Variation 18.2 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib Metabolite (LHY746)
All enrolled participants (n=3) received at least two doses of Encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Area under the curve of Encorafenib metabolite (LHY746) was assessed after single and repeated administrations. AUC0-tlast = area under the concentration curve from time 0 to time of last measurable concentration
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | Cycle 1 Day 1 AUC0-tlast | 2540 h*ng/mL | Standard Deviation 1150 |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Area Under the Curve (AUC) After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | Cycle 2 Day 1 AUC0-tlast | 6020 h*ng/mL | Standard Deviation 3330 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Maximum Concentration of encorafenib metabolite (LHY746) was assessed after single and repeated administrations.
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib | Cycle 1 Day 1 Cmax | 610 ng/mL | Standard Deviation 247 |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Maximum Concentration (Cmax) After Single and Repeated Administration of Encorafenib | Cycle 2 Day 1 Cmax | 1420 ng/mL | Standard Deviation 582 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Minimum concentration of encorafenib metabolite (LHY746) was assessed after single and repeated administrations.
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib | Cycle 1 Day 1 Cmin | NA ng/mL | — |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib | Cycle 2 Day 1 Cmin | 109 ng/mL | Standard Deviation 91.7 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): MRAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746)
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The MRAUC of encorafenib metabolite (LHY746) was assessed after single and repeated administrations. MRAUC = Metabolite Parent ratio based on AUC0-6
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetics Set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): MRAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | Cycle 1 Day 1 | 0.141 ratio | Geometric Coefficient of Variation 53.1 |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): MRAUC After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | Cycle 2 Day 1 | 0.730 ratio | Geometric Coefficient of Variation 41.3 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib Metabolite (LHY746)
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The time taken to reach maximum concentration of Encorafenib Metabolite (LHY746) was assessed after single and repeated administrations.
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | Cycle 1 Day 1 tmax | 5.98 hours |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib Metabolite (LHY746): Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib Metabolite (LHY746) | Cycle 2 Day 1 tmax | 2.00 hours |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib: Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The Minimum concentration of encorafenib was assessed after single and repeated administrations.
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: pharmacokinetic set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib | Cycle 1 Day 1 Cmin | NA ng/mL | — |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Minimum Concentration (Cmin) After Single and Repeated Administration of Encorafenib | Cycle 2 Day 1 Cmin | 10.5 ng/mL | Standard Deviation 6.76 |
Secondary
Plasma Pharmacokinetics (PK) of Encorafenib: Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib
All enrolled participants (n=3) received at least two doses of encorafenib, did all the planned PK blood collection with associated bioanalytical results and were therefore included in the PK Set. The time taken to reach maximum concentration of Encorafenib was assessed after single and repeated administrations.
Time frame: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle was 28 days.
Population: Pharmacokinetic Set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib | Cycle 1 Day 1 tmax | 2.00 hours |
| Encorafenib | Plasma Pharmacokinetics (PK) of Encorafenib: Time Taken to Reach Maximum Concentration (Tmax) After Single and Repeated Administration of Encorafenib | Cycle 2 Day 1 tmax | 1.00 hours |