Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

LGX818 will be dosed on a flat scale of 300 mg (e.g., 3 x 100 mg capsules) once daily on a continuous dosing cycle. A complete treatment cycle is defined as 28 days. There will be no breaks between dosing cycles.

LGX818

Pfizer CT.gov Call Center

The purpose of this signal seeking study is to determine whether treatment with LGX818 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study

LGX818 for Patients With BRAFV600 Mutated Tumors

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 4 - LGX818 for Patients With BRAFV600 Mutated Tumors

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

CBR for solid tumors was defined as percentage of participants with complete response (CR) or partial response (PR), or stable disease (SD) for greater than or equal to (\>=) 16 weeks. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

ORR for solid tumors was defined as the percentage of participants achieving an overall best response of CR or PR as assessed per RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

PFS for solid tumors was defined as the time from the date of first dose of study drug to the date of first documented disease progression (PD) or relapse or death due to any cause within 30 days of the last dose. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Participants who had no event were censored at the date of last adequate tumor assessment.

OS for solid tumors was defined as the time from the date of first dose of study drug to the date of death due to any cause. For participants who were alive at the time of analysis, the data was censored at the date of last contact.

DOR for solid tumors was defined as the time from the first documented response (CR or PR) to the date of first documented PD or relapse or death due to any cause, whichever occurred first. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. TEAE was defined as event with onset dates occurring during the on-treatment period. CTCAE Grade 5 (death) was not used in this study.

Change from baseline in systolic and diastolic blood pressure in millimeter of mercury (mmHg) in sitting position was reported.

Change from baseline in pulse rate in beats per minute (bpm) in sitting position was reported.

Change from baseline in body temperature in degree Celsius was reported.

Change from baseline in respiratory rate in breaths per minute was reported.

Change from baseline in body weight in kilogram (Kg) was reported

Number of participants with shifts from baseline in hematology and serum chemistry laboratory parameters, were graded and reported as low, normal and high as assessed by Common terminology criteria for adverse events (CTCAE) v4.03. 'Low' refers to participants with values that were below lower limit of normal with no observation above the upper limit of normal; 'High' refers to participants with values that were above the upper limit of normal with no observation below the lower limit of normal; 'Low and High' refers to participants with values that were below the lower limit of normal and values that were above the upper limit of normal.

Change from baseline in QTcF, QT, QRS, and PR duration were reported. QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization. PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.

Change from baseline in heart rate in terms of beats per minute was reported.

Pfizer

Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.

Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.

LGX818 (Encorafenib)

Age, Continuous

Sex: Female, Male

The full analysis set included all participants who received at least one dose of study drug.

Due to slow enrollment and lack of response observed during the enrollment period, the Sponsor decided to close study enrollment early on 28 January 2015.

Pfizer ClinicalTrials.gov Call Center

Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1

Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1

Overall Survival (OS) for Solid Tumors

Data for this outcome measure was not analyzed due to low overall response rate among participants.

Duration of Response (DOR) for Solid Tumors as Per RECIST Version 1.1

Grade 1

Grade 2

Grade 3

Grade 4

The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03

Systolic Blood Pressure: Baseline

Systolic Blood Pressure: Change at Cycle 2, Day 1

Systolic Blood Pressure: Change at Cycle 3, Day 1

Systolic Blood Pressure: Change at Cycle 4, Day 1

Systolic Blood Pressure: Change at Cycle 5, Day 1

Systolic Blood Pressure: Change at Cycle 6, Day 1

Systolic Blood Pressure: Change at Cycle 7, Day 1

Systolic Blood Pressure: Change at Cycle 8, Day 1

Systolic Blood Pressure: Change at Cycle 9, Day 1

Systolic Blood Pressure: Change at Cycle 10, Day 1

Systolic Blood Pressure: Change at Cycle 11, Day 1

Systolic Blood Pressure: Change at Cycle 12, Day 1

Systolic Blood Pressure: Change at End of Treatment

Diastolic Blood Pressure: Baseline

Diastolic Blood Pressure: Change at Cycle 2, Day 1

Diastolic Blood Pressure: Change at Cycle 3, Day 1

Diastolic Blood Pressure: Change at Cycle 4, Day 1

Diastolic Blood Pressure: Change at Cycle 5, Day 1

Diastolic Blood Pressure: Change at Cycle 6, Day 1

Diastolic Blood Pressure: Change at Cycle 7, Day 1

Diastolic Blood Pressure: Change at Cycle 8, Day 1

Diastolic Blood Pressure: Change at Cycle 9, Day 1

Diastolic Blood Pressure: Change at Cycle 10, Day 1

Diastolic Blood Pressure: Change at Cycle 11, Day 1

Diastolic Blood Pressure: Change at Cycle 12, Day 1

Diastolic Blood Pressure: Change at End of Treatment

The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.

Change From Baseline in Systolic and Diastolic Blood Pressure

Baseline

Change at Cycle 2, Day 1

Change at Cycle 3, Day 1

Change at Cycle 4, Day 1

Change at Cycle 5, Day 1

Change at Cycle 6, Day 1

Change at Cycle 7, Day 1

Change at Cycle 8, Day 1

Change at Cycle 9, Day 1

Change at Cycle 10, Day 1

Change at Cycle 11, Day 1

Change at Cycle 12, Day 1

Change at End of Treatment

Change From Baseline in Sitting Pulse Rate

Change From Baseline in Body Temperature

Change From Baseline in Respiratory Rate

Change From Baseline in Body Weight

Red Blood Cell Count, Low

Red Blood Cell Count, Normal

Red Blood Cell Count, High

Hematocrit, Low

Hematocrit, Normal

Hematocrit, High

Eosinophils, Low

Eosinophils, Normal

Eosinophils, High

Basophils, Low

Basophils, Normal

Basophils, High

Monocytes, Low

Monocytes, Normal

Monocytes, High

Neutrophils, Low

Neutrophils, Normal

Neutrophils, High

Lymphocytes, Low

Lymphocytes, Normal

Lymphocytes, High

Blood Urea Nitrogen, Low

Blood Urea Nitrogen, Normal

Blood Urea Nitrogen, High

Bicarbonate, Low

Bicarbonate, Normal

Bicarbonate, High

Lactate Dehydrogenase, Low

Lactate Dehydrogenase, Normal

Lactate Dehydrogenase, High

Serum Total Protein, Low

Serum Total Protein, Normal

Serum Total Protein, High

Low-Density Lipoprotein, Low

Low-Density Lipoprotein, Normal

Low-Density Lipoprotein, High

High-Density Lipoprotein, Low

High-Density Lipoprotein, Normal

High-Density Lipoprotein, High

Thyroid-Stimulating Hormone, Low

Thyroid-Stimulating Hormone, Normal

Thyroid-Stimulating Hormone, High

T3, Low

T3, Normal

T3, High

T4, Low

T4, Normal

T4, High

Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities

QTcF: Baseline

QTcF: Change at Cycle 1, Day 15

QTcF: Change at Cycle 2, Day 1

QTcF: Change at Cycle 2, Day 15

QTcF: Change at Cycle 3, Day 1

QTcF: Change at Cycle 4, Day 1

QTcF: Change at Cycle 5, Day 1

QTcF: Change at Cycle 6, Day 1

QTcF: Change at Cycle 7, Day 1

QTcF: Change at Cycle 8, Day 1

QTcF: Change at Cycle 9, Day 1

QTcF: Change at Cycle 10, Day 1

QTcF: Change at End of Treatment

QT: Baseline

QT: Change at Cycle 1, Day 15

QT: Change at Cycle 2, Day 1

QT: Change at Cycle 2, Day 15

QT: Change at Cycle 3, Day 1

QT: Change at Cycle 4, Day 1

QT: Change at Cycle 5, Day 1

QT: Change at Cycle 6, Day 1

QT: Change at Cycle 7, Day 1

QT: Change at Cycle 8, Day 1

QT: Change at Cycle 9, Day 1

QT: Change at Cycle 10, Day 1

QT: Change at End of Treatment

QRS: Baseline

QRS: Change at Cycle 1, Day 15

QRS: Change at Cycle 2, Day 1

QRS: Change at Cycle 2, Day 15

QRS: Change at Cycle 3, Day 1

QRS: Change at Cycle 4, Day 1

QRS: Change at Cycle 5, Day 1

QRS: Change at Cycle 6, Day 1

QRS: Change at Cycle 7, Day 1

QRS: Change at Cycle 8, Day 1

QRS: Change at Cycle 9, Day 1

QRS: Change at Cycle 10, Day 1

QRS: Change at End of Treatment

PR: Baseline

PR: Change at Cycle 1, Day 15

PR: Change at Cycle 2, Day 1

PR: Change at Cycle 2, Day 15

PR: Change at Cycle 3, Day 1

PR: Change at Cycle 4, Day 1

PR: Change at Cycle 5, Day 1

PR: Change at Cycle 6, Day 1

PR: Change at Cycle 7, Day 1

PR: Change at Cycle 8, Day 1

PR: Change at Cycle 9, Day 1

PR: Change at Cycle 10, Day 1

PR: Change at End of Treatment

Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration

Change at Cycle 1, Day 15

Change at Cycle 2, Day 15

Change From Baseline in Heart Rate

Overall Study

Spots Global Cancer Trial Database for LGX818 for Patients With BRAFV600 Mutated Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial