Solid Tumors Harboring a BRAF V600 MutationPhase 1/2NCT01543698

A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors

A Phase 1/2 study testing LGX818, MEK162 and LEE011 in people with Solid Tumors Harboring a BRAF V600 Mutation, run by Pfizer at 26 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Solid Tumors Harboring a BRAF V600 Mutation
What is being tested?: LGX818, MEK162 and LEE011
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 189 participants
Where: 26 sitesin 9 countries
Study dates: 28 May 2012to 9 Mar 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available
Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation
Evidence of measurable disease as determined by RECIST v1.1
World Health Organization (WHO) Performance Status ≤ 2
Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential

Who cannot join

Progressive disease following prior treatment with RAF-inhibitors in combination with MEK-inhibitors
Symptomatic or untreated leptomeningeal disease
Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing anti-epileptic drugs
Known acute or chronic pancreatitis
History or current evidence of retinal disease, retinal vein occlusion or ophthalmopathy
Clinically significant cardiac disease

Show all 12Show fewer

Patients with abnormal laboratory values at Screening/baseline
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818/MEK162
Previous or concurrent malignancy
Pregnant or nursing (lactating) women
For addition of LEE011 in the triple combination, congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3, brain metastases at baseline, abnormal coagulation results PT/INR >1.5 x ULN or aPTT >1.5 x ULN.
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

26 sites in 9 countries.

Country

City, postcode or hospital

26 sites in 9 countries

United States6 sites

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Massachusetts General Hospital
Boston, Massachusetts, 02114
Ophthalmic Consultants of Boston Inc (OCB)
Boston, Massachusetts, 02114
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, 33612
Moffitt McKinley Outpatient Center
Tampa, Florida, 33612

Other trials in United States

Australia6 sites

Chris O'Brien Lifehouse Hospital
Camperdown, New South Wales, 02050
Melanoma Institute Australia
North Sydney, New South Wales, 2060
Melanoma Institute Australia
North Sydney, 2065
Westmead Hospital-Redbank Rd
Northmead, New South Wales, 2152
Westmead Hospital-Redbank Rd
Westmead, New South Wales, 2145
Westmead Hospital
Westmead, New South Wales, 2145

Other trials in Australia

Italy5 sites

ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
Milan, 20162
Azienda Ospedaliera Monaldi
Naples, Campania, 80131
Azienda Ospedaliera Universitaria Federico II
Naples, Campania, 80131
IRCCS Fondazione Pascale
Naples, Campania, 80131
Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
Naples, 80131

Other trials in Italy

France2 sites

Hôpital Saint louis
Paris, 75010
Service de radiologie - Hopital Saint Louis
Paris, 75475

Other trials in France

Spain2 sites

Hospital Universitario Vall d'Hebrón - PPDS
Barcelona, 08035
Hospital Universitario HM Sanchinarro ? CIOCC
Madrid, 28050

Other trials in Spain

Switzerland2 sites

Kantonsspital St. Gallen
Sankt Gallen, 9007
University Hospital Zürich, Dermatology
Zurich-Airport, Canton of Zurich, 8058

Other trials in Switzerland

Belgium1 site

UZ Leuven- Gasthuisberg Campus
Leuven, Vlaams Brabant, 3000

Other trials in Belgium

Canada1 site

Sir Mortimer B. Davis-Jewish General Hospital
Montreal, Quebec, H3T 1E2

Other trials in Canada

Singapore1 site

National Cancer Centre Singapore
Singapore, 169610

Other trials in Singapore

About this study

Official title: A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors

This is a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the MTD(s) and/or RP2D(s) for the dual combination of LGX818 and MEK162 and the triple combination of LGX818 and MEK162 and LEE011, followed each independently by a Phase II part to assess the clinical efficacy and to further assess the safety of the combinations in selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous schedule. Oral LEE011 will be administered once daily on a three weeks on, one week off schedule. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. A cycle is defined as 28 days. The dose escalation parts of the trial will be conducted in adult patients with BRAF V600-dependent advanced solid tumors and is expected to enroll at least 18 patients for the dual combination and at least 12 patients for the triple combination. The dose escalation will be guided by a Bayesian logistic regression model (BLRM). Following MTD/RP2D declaration, patients will be enrolled in three Phase II arms for the dual combination and one Phase II arm for the triple combination. All patients will be followed for 30 days for safety assessments after study drugs discontinuation. All patients enrolled in the Phase II part of the study will be followed for survival.

Conditions: Solid Tumors Harboring a BRAF V600 Mutation
Being tested: LGX818, MEK162, LEE011
Keywords: Advanced solid tumor,, BRAF V600 mutation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LGX818Drug
MEK162Drug
LEE011Drug

Study groups in NCT01543698
Study group	Role	What they receive
dual combination	Experimental	LGX818 QD and MEK162 BID Receives: Drug: LGX818; Drug: MEK162
triple combination	Experimental	LGX818 QD and MEK162 BID and LEE011 QD 3 weeks on, 1 week off. Receives: Drug: LGX818; Drug: MEK162; Drug: LEE011

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b
DLT was defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, as clinically relevant, as unrelated to disease, disease progression, inter-current illness, or concomitant medications, which occurred (less than equal to) <=28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011 (cycle 1) and met the defined criteria for the study.
Measured: Phase 1b: Cycle 1 (28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011)
Disease Control Rate (DCR) at Week 16: Phase 2, Arm 1 (mCRC Participants)
DCR was defined as percentage of participants with a best overall response of complete response (CR), partial response (PR) or stable disease (SD). As per Response Evaluation Criteria in Solid tumors Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis less than (<)10 millimeter [mm]). PR was defined as more than equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD).
Measured: Phase 2: Week 16
Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A
ORR was defined as the percentage of participants with a best overall response of CR or PR. As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis <10 mm. PR was defined as >= 30% decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters.
Measured: Phase 2: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment for Phase 2 was 111.5 months]

Secondary outcomes (19)

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those events with onset dates occurring during the on-treatment period (the time from the Day 1 up to 30 days after last dose). AEs were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated. Grade 5 indicates death related to AE.
Measured: Phase 1b: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 1b was 118.3 months)
Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those events with onset dates occurring during the on-treatment period (the time from the Day 1 up to 30 days after last dose). AEs were graded according to CTCAE version 4.03 as Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated. Grade 5 indicates death related to AE.
Measured: Phase 2: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 2 was 111.5 months)
Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
AUCinf was reported in unit of measure as hour*nanogram per millilitre (h*ng/mL).
Measured: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hours (hr) post dose on Day 1 of Cycle 1
Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Measured: Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b
Accumulation ratio was calculated as AUCtau,ss/AUCtau.
Measured: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 and 15 of Cycle 1
Objective Response Rate (ORR): Phase 1b
ORR was defined as the percentage of participants with a best overall response of CR or PR. As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis <10 mm. PR was defined as >= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters.
Measured: Phase 1b: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment in Phase 1b was 118.3 months)
Progression Free Survival (PFS): Phase 2
PFS was defined as the time from the start of study treatment to the date of the event defined as the first documented progression or death due to any cause. If a participant did not have an event, PFS was censored at the date of last adequate tumor assessment. Per RECIST 1.1, PD= 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^2. Unequivocal progression of existing non-target lesions. Kaplan-Meier method was used for analysis.
Measured: Phase 2: From start of study drug until documented PD or death due to any cause or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)
Time to Response (TTR): Phase 2
TTR was defined as the time from the first dose of study treatment to the first documentation of objective tumor response documented in participants with confirmed objective response (CR or PR). As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis <10 mm. PR was defined as >= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. Kaplan-Meier method was used for analysis.
Measured: Phase 2: From date of start of treatment until date of first documentation of objective tumor response (maximum exposure of treatment in Phase 2 was 111.5 months)
Duration of Response (DOR): Phase 2
DOR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to underlying cancer, whichever occurred first in participants with confirmed objective response (CR or PR). As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis <10 mm. PR was defined as >= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. Kaplan-Meier method was used for analysis.
Measured: Phase 2: From date of first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to underlying cancer, whichever occurred first (maximum exposure of treatment in Phase 2 was 111.5 months)
Overall Survival (OS): Phase 2
OS was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last contact. Analysis was performed using Kaplan-Meier method.
Measured: Phase 2: From date of start of study treatment until date of death or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)
Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b
Molecular alterations of tumor tissues was determined using the following potential predictive markers: Biomarkers like V-raf murine sarcoma viral oncogene homolog B1 (BRAF),V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), Phosphatase and tensin homolog (PTEN), Phosphatidylinositol 3' kinase catalytic alphapolypeptide (PIK3CA), Epidermal growth factor receptor (EGFR).
Measured: Phase 1b: Baseline
Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2
Molecular alterations of tumor tissues was determined using the following potential predictive markers: BRAF, HRAS, KRAS, Neuroblastoma RAS viral oncogene homolog (NRAS), PTEN, PIK3CA, Mitogen-activated protein kinase 1 (MAP2K1), Mitogen-activated protein kinase 2 (MAP2K2), EGFR.
Measured: Phase 2: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

28 May 20129 Mar 2023

First posted5 Mar 2012 (estimated)
Study start28 May 2012
Primary completion9 Mar 2023
Study completion9 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Solid Tumors Harboring a BRAF V600 MutationStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Other
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 189 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01543698
Sponsor's protocol ID: CMEK162X2110
Other IDs: C4221005, 2011-005875-17
Status last verified: Feb 2024
First submitted: 1 Feb 2012
Last updated: 13 Mar 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: 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.

Publications

Sullivan RJ, Weber J, Patel S, Dummer R, Carlino MS, Tan DSW, Lebbe C, Siena S, Elez E, Wollenberg L, Pickard MD, Sandor V, Ascierto PA. A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Clin Cancer Res. 2020 Oct 1;26(19):5102-5112. doi: 10.1158/1078-0432.CCR-19-3550. Epub 2020 Jul 15.
PubMed 32669376

Study at a glance

From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors
ClinicalTrials.gov ID: NCT01543698
Acronym / sponsor ID: CMEK162X2110
Conditions: Solid Tumors Harboring a BRAF V600 Mutation
Keywords: Advanced solid tumor,, BRAF V600 mutation
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 189 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 28 May 2012 (actual)
Primary completion: 9 Mar 2023 (actual)
Study completion: 9 Mar 2023 (actual)
First posted: 5 Mar 2012 (estimated)
Results: Posted 13 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
dual combination	Experimental	Drug: LGX818, Drug: MEK162LGX818 QD and MEK162 BID
triple combination	Experimental	Drug: LGX818, Drug: MEK162, Drug: LEE011LGX818 QD and MEK162 BID and LEE011 QD 3 weeks on, 1 week off.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available
Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation
Evidence of measurable disease as determined by RECIST v1.1
World Health Organization (WHO) Performance Status ≤ 2
Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential

Key exclusion criteria (12 listed)

Progressive disease following prior treatment with RAF-inhibitors in combination with MEK-inhibitors
Symptomatic or untreated leptomeningeal disease
Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing anti-epileptic drugs
Known acute or chronic pancreatitis
History or current evidence of retinal disease, retinal vein occlusion or ophthalmopathy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LGX818	Drug	dual combination, triple combination
MEK162	Drug	dual combination, triple combination
LEE011	Drug	triple combination

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b
Time frame: Phase 1b: Cycle 1 (28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011)
DLT was defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, as clinically relevant, as unrelated to disease, disease progression, inter-current illness, or concomitant medications, which occurred (less than equal to) <=28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011 (cycle 1) and met the defined criteria for the study.
Disease Control Rate (DCR) at Week 16: Phase 2, Arm 1 (mCRC Participants)
Time frame: Phase 2: Week 16
DCR was defined as percentage of participants with a best overall response of complete response (CR), partial response (PR) or stable disease (SD). As per Response Evaluation Criteria in Solid tumors Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis less than (<)10 millimeter [mm]). PR was defined as more than equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD).
Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A
Time frame: Phase 2: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment for Phase 2 was 111.5 months]
ORR was defined as the percentage of participants with a best overall response of CR or PR. As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis <10 mm. PR was defined as >= 30% decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters.

19 secondary outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b
Time frame: Phase 1b: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 1b was 118.3 months)
Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2
Time frame: Phase 2: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 2 was 111.5 months)
Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hours (hr) post dose on Day 1 of Cycle 1
Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1
t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1
Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b
Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 and 15 of Cycle 1
Objective Response Rate (ORR): Phase 1b
Time frame: Phase 1b: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment in Phase 1b was 118.3 months)
Progression Free Survival (PFS): Phase 2
Time frame: Phase 2: From start of study drug until documented PD or death due to any cause or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)
Time to Response (TTR): Phase 2
Time frame: Phase 2: From date of start of treatment until date of first documentation of objective tumor response (maximum exposure of treatment in Phase 2 was 111.5 months)
Duration of Response (DOR): Phase 2
Time frame: Phase 2: From date of first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to underlying cancer, whichever occurred first (maximum exposure of treatment in Phase 2 was 111.5 months)
Overall Survival (OS): Phase 2
Time frame: Phase 2: From date of start of study treatment until date of death or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)
Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b
Time frame: Phase 1b: Baseline
Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2
Time frame: Phase 2: Baseline

Results and safety

Results posted to the registry on 13 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	6	0
Phase 1b: Encorafenib 100 mg+ Binimetinib 45 mg	5	0
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	4	0
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	5	0
Phase 1b: Encorafenib 450 mg+ Binimetinib 45 mg	13	0
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	8	0
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	6	0
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 100 mg	4	0
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 200 mg	5	0
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	6	0
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg + Ribociclib 600 mg	6	0
Phase 2: Arm 1 (mCRC): Encorafenib + Binimetinib	0	0
Phase 2: Arm 2 (Prior BRAFi Melanoma): Encorafenib + Binimetinib	0	0
Phase 2: Arm 3 (BRAFi-naïve Melanoma): Encorafenib + Binimetinib	0	0
Phase 2: Arm A (BRAFi-naïve Melanoma): Encorafenib + Binimetinib + Ribociclib	0	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b

Time frame: Phase 1b: Cycle 1 (28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011). Count of participants. Unit: Participants

Measure	Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg n = 6	Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg n = 5	Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg n = 2	Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg n = 4	Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg n = 13	Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg n = 8	Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg n = 6	Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg n = 4	Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg n = 5	Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg n = 5	Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg n = 5
Value	0	0	0	0	0	0	1	0	0	0	0

Population analysed: Dose Determining Set (DDS) included all Phase 1b participants from the safety set who either completed a minimum exposure requirement and had sufficient safety evaluations or discontinued prematurely due to a DLT. All participants reported under "Number of Participants Analyzed" contributed data to this outcome measure.

Primary outcome: Disease Control Rate (DCR) at Week 16: Phase 2, Arm 1 (mCRC Participants)

Time frame: Phase 2: Week 16. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Phase 2: Arm 1 (mCRC): Encorafenib + Binimetinib n = 11
Value	63.6 (30.8 to 89.1)

Population analysed: Full Analysis Set (FAS) included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Primary outcome: Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A

Time frame: Phase 2: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment for Phase 2 was 111.5 months]. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Phase 2: Arm 2 (Prior BRAFi Melanoma): Encorafenib + Binimetinib n = 26	Phase 2: Arm 3 (BRAFi-naïve Melanoma): Encorafenib + Binimetinib n = 42	Phase 2: Arm A (BRAFi-naïve Melanoma): Encorafenib + Binimetinib + Ribociclib n = 42
Value	42.3 (23.4 to 63.1)	66.7 (50.5 to 80.4)	59.5 (43.3 to 74.4)

Population analysed: FAS included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 of dosing up to 30 days after last dose (maximum treatment exposure for Phase 1b was 118.3 months, Phase 2 was 111.5 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	4 of 6 (66.7%)	6 of 6 (100%)	1 of 6
Phase 1b: Encorafenib 100 mg+ Binimetinib 45 mg	2 of 5 (40%)	5 of 5 (100%)	0 of 5
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	2 of 4 (50%)	4 of 4 (100%)	1 of 4
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	2 of 5 (40%)	5 of 5 (100%)	2 of 5
Phase 1b: Encorafenib 450 mg+ Binimetinib 45 mg	5 of 13 (38.5%)	13 of 13 (100%)	2 of 13
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	4 of 8 (50%)	8 of 8 (100%)	0 of 8
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	4 of 6 (66.7%)	6 of 6 (100%)	1 of 6
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 100 mg	2 of 4 (50%)	4 of 4 (100%)	0 of 4
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 200 mg	3 of 5 (60%)	5 of 5 (100%)	1 of 5
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	3 of 6 (50%)	5 of 6 (83.3%)	0 of 6
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg + Ribociclib 600 mg	2 of 6 (33.3%)	6 of 6 (100%)	2 of 6
Phase 2: Arm 1 (mCRC): Encorafenib + Binimetinib	5 of 11 (45.5%)	11 of 11 (100%)	9 of 11
Phase 2: Arm 2 (Prior BRAFi Melanoma): Encorafenib + Binimetinib	13 of 26 (50%)	26 of 26 (100%)	22 of 26
Phase 2: Arm 3 (BRAFi-naïve Melanoma): Encorafenib + Binimetinib	18 of 42 (42.9%)	39 of 42 (92.9%)	22 of 42
Phase 2: Arm A (BRAFi-naïve Melanoma): Encorafenib + Binimetinib + Ribociclib	21 of 42 (50%)	42 of 42 (100%)	28 of 42

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32669376Sullivan RJ, Weber J, Patel S, Dummer R, Carlino MS, Tan DSW, Lebbe C, Siena S, Elez E, Wollenberg L, Pickard MD, Sandor V, Ascierto PA. A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with BRAFV600E/K -mutant Solid Tumors. Clin Cancer Res. 2020 Oct 1;26(19):5102-5112. doi: 10.1158/1078-0432.CCR-19-3550. Epub 2020 Jul 15.
Individual participant dataSharing planned: Yes. 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer Pfizer CT.gov Call Center study director

Pfizer

26 sites in 9 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LGX818, MEK162 and LEE011 in people with Solid Tumors Harboring a BRAF V600 Mutation, run by Pfizer at 26 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Australia, Italy, France, Spain and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b (time frame: Phase 1b: Cycle 1 (28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01543698, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.