A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma

August 13, 2024 updated by: Pfizer

A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma

CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
107

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Western Sydney Local Health District
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital- Redbank Rd
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Peter MacCallum Cancer Centre
  • France
      • Villejuif, France, 94805
        • Institut Gustave Roussy
    • Haute-garonne
      • Toulouse, Haute-garonne, France, 31059 Cedex 9
        • EDOG - Institut Claudius Regaud - PPDS
    • ILE DE France - VAL DE Marne (94)
      • Villejuif, ILE DE France - VAL DE Marne (94), France, 94800
        • Institut Gustave Roussy
    • VAL DE Marne
      • Villejuif, VAL DE Marne, France, 94800
        • Institut Gustave Roussy
    • Val-de-marne
      • Villejuif, Val-de-marne, France, 94805
        • Institut Gustave Roussy
      • Villejuif Cedex, Val-de-marne, France, 94805
        • Institut Gustave Roussy
  • Japan
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
  • Norway
      • Oslo, Norway, 00424
        • Oslo Myeloma Center - PPDS
  • Spain
      • Badalona, Spain, 08036
        • Hospital Clínic de Barcelona
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron - PPDS
      • Barcelona, Spain, 08035
        • Hospital General Vall D'Hebron
      • Barcelona, Spain, 8035
        • Hospital Universitario Vall d'Hebron - PPDS
      • Madrid, Spain, 28050
        • Hospital Universitario HM Sanchinarro_CIOCC
      • Madrid, Spain, 28050
        • START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
  • Switzerland
      • Zürich, Switzerland, 8091
        • Universität Zürich
    • Graubünden (DE)
      • Chur, Graubünden (DE), Switzerland, 07000
        • Kantonsspital Graubunden
  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H Lee Moffitt Cancer Center and Research Institute
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

For the dose escalation phase:

  1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii) confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC) for which no further effective standard therapy exists.
  2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
  3. Evidence of measurable disease

Exclusion Criteria:

  1. Previous therapy with a MEK inhibitor.
  2. Symptomatic or untreated leptomeningeal disease.
  3. Symptomatic or untreated brain metastasis.Patients previously treated for these conditions that are asymptomatic in the absence of corticosteroid therapy are allowed to enroll. Brain metastasis must be stable with verification by imaging.
  4. Known acute or chronic pancreatitis.
  5. Clinically significant cardiac disease
  6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
  7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include: adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to study entry; or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry.
  8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
  9. History of thromboembolic or cerebrovascular events within the last 6 months

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LGX818 - Dose escalation
Drug: LGX818
Experimental: LGX818 - Dose Expansion at MTD or RP2D
Drug: LGX818

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase
Time Frame: Up to 28 days
DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: >=grade (G)3 neutropenia or thrombocytopenia for >7 days; G4 thrombocytopenia; febrile neutropenia; >=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (>=G3 for > 7 consecutive days or G4); >=G3 ALT or AST and >=G2 blood bilirubin; >=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for >7 consecutive days; >= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; >=G3 pancreatitis, rash/photosensitivity (G3 for > 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.
Up to 28 days
Number of Participants With DLT During Dose Expansion Phase
Time Frame: Up to 28 days
DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: >=grade (G)3 neutropenia or thrombocytopenia for >7 days; G4 thrombocytopenia; febrile neutropenia; >=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (>=G3 for > 7 consecutive days or G4); >=G3 ALT or AST and >=G2 blood bilirubin; >=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for >7 consecutive days; >= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; >=G3 pancreatitis, rash/photosensitivity (G3 for > 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.
Up to 28 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Dose Escalation Phase
Time Frame: From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure)
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions. An SAE was defined as one of the following: fatal or life-threatening; resulted in significant disability/incapacity; congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization unless for routine treatment, elective or pre-planned treatment for a pre-existing condition, treatment on an emergency outpatient basis, social reasons and respite care in the absence of any deterioration in the participants general condition, any SAEs that were expected due to the condition being treated.
From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure)
Number of Participants With AEs and SAEs During Dose Expansion Phase
Time Frame: From start of study treatment until 30 days after last dose of study treatment (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions. An SAE was defined as one of the following: fatal or life-threatening; resulted in significant disability/incapacity; congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization unless for routine treatment, elective or pre-planned treatment for a pre-existing condition, treatment on an emergency outpatient basis, social reasons and respite care in the absence of any deterioration in the participants general condition, any SAEs that were expected due to the condition being treated.
From start of study treatment until 30 days after last dose of study treatment (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Progression Free Survival (PFS): Dose Escalation Phase
Time Frame: From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)
PFS was defined as time from date of first study treatment intake to date of first documented disease progression (PD) or death due to any cause. If a participant did not have an event, data censoring was done at the date of last adequate tumor assessment. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of greater than or equal to (>=) 5 mm, or appearance of >=1 new lesions. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier method.
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)
PFS: Dose Expansion Phase
Time Frame: From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
PFS was defined as time from date of first study treatment intake to date of first documented PD or death due to any cause. If a participant did not have an event, data censoring was done at the date of last adequate tumor assessment. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier method.
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Duration of Response (DOR): Dose Escalation Phase
Time Frame: From first observation of response until first time of PD or death due to any cause (Maximum of 556.1 weeks of treatment exposure)
DOR was defined as the time from first observation of response CR or partial response [PR]) to the first time of progression or death. CR was defined as complete disappearance of all target and non-target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
From first observation of response until first time of PD or death due to any cause (Maximum of 556.1 weeks of treatment exposure)
Time to Response (TTR): Dose Escalation Phase
Time Frame: From date of start of treatment until CR or PR or censoring date (maximum of 556.1 weeks of treatment exposure)
TTR was defined as the time from date of treatment until first documented response (CR or PR). CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease) or at maximum follow-up (from study start to study end date) when participant had an event for progression-free survival. Individual participant data have been reported for this outcome measure.
From date of start of treatment until CR or PR or censoring date (maximum of 556.1 weeks of treatment exposure)
DOR: Dose Expansion Phase
Time Frame: From first observation of response until first time of PD or death due to any cause (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
DOR was defined as the time from first observation of response (CR or PR] to the first time of progression or death. CR was defined as complete disappearance of all target and non-target lesions and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to (<10 mm. PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
From first observation of response until first time of PD or death due to any cause (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
TTR: Dose Expansion Phase
Time Frame: From date of start of treatment until CR or PR or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
TTR was defined as the time from date of treatment until first documented response (CR or PR). CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease) or at maximum follow-up (from study start to study end date) when participant had an event for progression-free survival. Individual participant data have been reported for this outcome measure.
From date of start of treatment until CR or PR or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Overall Survival (OS): Dose Expansion Phase
Time Frame: From start of study treatment until date of death or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Overall survival was defined as the time from the date of first study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
From start of study treatment until date of death or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Maximum Observed Plasma Concentration of LGX818: Dose Escalation Phase
Time Frame: Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Time Point of Maximum Concentration (Tmax) of LGX818: Dose Escalation Phase
Time Frame: Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of LGX818: Dose Escalation Phase
Time Frame: Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
AUC (inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Area Under the Concentration-Time Curve From Time Zero to Tau (AUCtau) of LGX818: Dose Escalation Phase
Time Frame: Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Elimination Half-life (t1/2) of LGX818: Dose Escalation Phase
Time Frame: Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
t1/2 was the time measured for the plasma concentration to decrease by one half. Terminal phase half-life expressed in hours (hr).
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Apparent Total Plasma Clearance of Drug (CL/F) of LGX818: Dose Escalation Phase
Time Frame: Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Apparent Volume of Distribution (Vz/F) of LGX818: Dose Escalation Phase
Time Frame: Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Number of Participants According to Tumor Response Per RECIST Criteria- Dose Escalation
Time Frame: From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)
Tumor response included: CR, PR, stable disease and disease progression (PD). CR=complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR=at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)
Maximum Observed Plasma Concentration of LGX818: Dose Expansion Phase
Time Frame: Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Vz/F of LGX818: Dose Expansion Phase
Time Frame: Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Tmax of LGX818: Dose Expansion Phase
Time Frame: Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Tmax was the time required to reach the maximum plasma concentration (Cmax). First observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in hours (hr).
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
AUCinf of LGX818: Dose Expansion Phase
Time Frame: Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
AUC (inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
AUCtau of LGX818: Dose Expansion Phase
Time Frame: Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
t1/2 of LGX818: Dose Expansion Phase
Time Frame: Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
CL/F of LGX818: Dose Expansion Phase
Time Frame: Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Number of Participants According to BRAF V600 Mutation Status at Baseline: Dose Expansion
Time Frame: (Baseline) last non-missing value prior to the first dose (Baseline)
Number of participants according to BRAF V600 mutation status as V600E (i.e., mutation of the BRAF gene in which valine [V] was substituted by glutamic acid [E] at amino acid 600) or other is reported in this outcome measure.
(Baseline) last non-missing value prior to the first dose (Baseline)
Number of Participants According to Tumor Response Per RECIST Criteria: Dose Expansion
Time Frame: From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
umor response included: CR, PR, stable disease and disease progression (PD). CR=complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR=at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Pfizer CT.gov Call Center, Pfizer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 5, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 7, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 14, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2011

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 20, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 13, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLGX818X2101
  • C4221010 (Other Identifier: Alias Study Number)
  • 2011-000556-42 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Melanoma and Metastatic Colorectal Cancer

Clinical Trials on LGX818

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings