MelanomaPhase 2LOGIC-2NCT02159066
LGX818 and MEK162 in Combination With a Third Agent (BKM120, LEE011, BGJ398 or INC280) in Advanced BRAF Melanoma
A Phase 2 study testing LGX818, MEK162 and LEE011 in people with Melanoma, run by Pfizer at 32 sites in 9 countries.
Trial summary
The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- LGX818, MEK162 and LEE011
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 158 participants
- Where
- 32 sitesin 9 countries
- Study dates
- 23 Jul 2014to 10 Jan 2023
- Phase
- Phase 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
- Age ≥ 18 years
- Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer [AJCC])
- Documented evidence of BRAF V600 mutation.
- Newly obtained tumor biopsy at baseline, and patient agrees to a mandatory biopsy at the time of progression, if not medically contraindicated.
- Evidence of measurable disease, as determined by RECIST v1.1.
- Progressive disease following prior treatment with LGX818/MEK162 combination. PRINCIPAL EXCLUSION CRITERIA Symptomatic or untreated leptomeningeal disease.
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- Symptomatic brain metastases. Patients previously treated or untreated for brain metastases that are asymptomatic in the absence of corticosteroid therapy or on a stable dose of steroids for four weeks are allowed to enroll. Brain metastases must be stable at least 4 weeks with verification by imaging (e.g. brain MRI completed at screening demonstrating no current evidence of progressive brain metastases). Patients are not permitted to receive enzyme inducing anti-epileptic drugs.
- Patients who have developed brain metastases during Part I of the study may continue to Part II upon discussion with Novartis Medical Monitor. The brain metastasis must be either asymptomatic or treated and stable for at least 4 weeks and on a stable or tapering dose of steroids for at least 2 weeks. Patients with brain metastasis are not eligible for the combination with LEE011.
- Known acute or chronic pancreatitis.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes);
- Clinically significant cardiac disease including any of the following:
- CHF requiring treatment (NYH grade ≥ 2),
- LVEF < 50% as determined by MUGA scan or ECHO
- History or presence of clinically significant ventricular arrhythmias or atrial fibrillation
- Clinically significant resting bradycardia
- Unstable angina pectoris ≤ 3 months prior to starting study drug
- Acute Myocardial Infarction (AMI) ≤ 3 months prior to starting study drug,
- QTcF > 480 msec. Patients with any of the following laboratory values at
- Screening/baseline:
- Absolute neutrophil count (ANC) <1,500/mm3 [1.5 x 109/L]
- Platelets < 100,000/mm3 [100 x 109/L]
- Hemoglobin < 9.0 g/dL
- Serum creatinine >1.5 x ULN or calculated or directly measured CrCl < 50% LLN (lower limit of normal)
- Serum total bilirubin >1.5 x ULN
- AST/SGOT or ALT/SGPT > 2.5 x ULN, or > 5 x ULN if liver metastases are present
- Additional exclusion criteria for the triple combinations:
- LGX818/MEK162/BKM120:
- Patients with fasting glucose > 120 mg/dL or 6.7 mmol/L, and HbA1c > 8 %.
- Patient has any of the following mood disorders as judged by the
- Investigator or a Psychiatrist:
- Patient has a score ≥ 12 on the PHQ-9 questionnaire
- Patient has ≥ CTCAE grade 3 anxiety
- LGX818/MEK162/BGJ398:
- History and/or current evidence of significant ectopic mineralization/ calcification with the exception of calcified lymph nodes and asymptomatic vascular calcification.
- Current evidence of corneal disorder/ keratopathy incl. but not limited to bullous/ band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivits etc., confirmed by ophthalmologic examination
- LGX818/MEK162/LEE011:
- Patients with uncontrolled hypertension (please refer to WHO-ISHguidelines) are excluded from study.
- QTcF >450 ms for males and >470 ms for females Congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3 and magnesium levels below the clinically relevant lower limits at study entry
- Current evidence of brain metastasis or brain metastasis detected by mandatory CT/MRI at screening
- PT/INR or aPTT > 1.5xULN
- Other protocol-defined inclusion/exclusion criteria may apply.
Who cannot join
None listed.
Trial locations and contacts
32 sites in 9 countries.
32 sites in 9 countries
United States17 sites
University of California Los Angeles
Los Angeles, California, 90024
Cancer Care Center
Los Angeles, California, 90095
Doris Stein Research Center Building
Los Angeles, California, 90095
Ronald Reagan UCLA Medical Center Drug Information Center Department of Pharmaceutical Services
Los Angeles, California, 90095
UCLA Dermatology Clinic
Los Angeles, California, 90095
UCLA Oncology Center
Los Angeles, California, 90095
UCLA Radiology
Los Angeles, California, 90095
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center Attn: Geny O'neill
New York, New York, 10065
Memorial Sloan Kettering Cancer Center Inpatient Hospital & Main Campus
New York, New York, 10065
Memorial Sloan Kettering Cancer Center- Outpatient Clinic
New York, New York, 10065
OHSU Knight Cancer Institute
Portland, Oregon, 97201
OHSU Center for Health and Healing 2
Portland, Oregon, 97239
OHSU Center for Health and Healing
Portland, Oregon, 97239
OHSU Research Pharmacy Services
Portland, Oregon, 97239
Oregon Health and Science University
Portland, Oregon, 97239
Germany5 sites
Uniklinik Köln
Cologne, 50937
University Clinic Heidelberg PPDS
Heidelberg, Baden-Wurttemberg, 69120
Städtisches Klinikum München
München, 80337
Universitätsklinikum Würzburg
Würzburg, Bavaria, 97080
Universitätsklinikum Würzburg
Würzburg, 97080
Australia2 sites
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
East St Kilda Eye Clinic
Melbourne, Victoria, 3183
Canada2 sites
Sir Mortimer B. Davis-Jewish General Hospital
Monteral, Quebec, H3T 1E2
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9
Italy2 sites
Azienda Ospedaliera Monaldi
Naples, Campania, 80131
U.O.C. Oncologia Medica e Terapie Innovative Dipartimento di Melanoma IRCCS Fondazione G. Pascale
Naples, 80131
Netherlands1 site
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
Amsterdam, 1066 CX
Spain1 site
Hospital Universitario Vall d'Hebrón - PPDS
Barcelona Cataluna, Barcelona, 08035
About this study
Official title: The LOGIC 2 Trial A Phase II, Multi-center, Open-label Study of Sequential LGX818/MEK162 Combination Followed by a Rational Combination With Targeted Agents After Progression, to Overcome Resistance in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma.
The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations.
Read the detailed description
This study consists of two parts: in Part I/Run-In, patients naïve to selective BRAF and MEK inhibitors will be treated with the LGX818/MEK162 combination until disease progression (as defined per RECIST v1.1). Based on the genetic analysis of a tumor biopsy obtained at that time, patients will enter Part II of the study for tailored combination treatment in one of four arms of LGX818/MEK162 + either BKM120, BGJ398, INC280 or LEE011 Patients with BRAF mutant melanoma treated by LGX818/MEK162 combination in other studies can be enrolled directly in Part II of CLGX818X2109 after relapse.
Dose-escalations in the combination arms for which no MTD has been established will be based on the recommendations of a Bayesian logistic regression model guided by an escalation with overdose control criterion
- Conditions
- Melanoma
- Being tested
- LGX818, MEK162, LEE011, BGJ398, BKM120
- Keywords
- Melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LGX818Drug
Combination of LGX818 and MEK162 (Part I)
MEK162Drug
Combination of LGX818 and MEK162 (Part I)
LEE011Drug
Combination of LGX818 + MEK162 + LEE011 (Part II)
BGJ398Drug
Combination of LGX818 + MEK162 + BGJ398 (Part II)
BKM120Drug
Combination of LGX818 + MEK162 + BKM120 (Part II)
INC280Drug
Combination of LGX818 + MEK162 + INC280 (Part II)
| Study group | Role | What they receive |
|---|---|---|
| LGX818 + MEK162 | Experimental | Not described Receives: Drug: LGX818; Drug: MEK162 |
| LGX818 + MEK162 + LEE011 | Experimental | Not described Receives: Drug: LEE011 |
| LGX818 + MEK162 + BGJ398 | Experimental | Not described Receives: Drug: BGJ398 |
| LGX818 + MEK162 + BKM120 | Experimental | Not described Receives: Drug: BKM120 |
| LGX818 + MEK162 + INC280 | Experimental | Not described Receives: Drug: INC280 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR): Part II
ORR: percentage of participants with confirmed complete response (CR) and partial response (PR). Response evaluation criteria in solid tumors (RECIST) v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions that had a reduction in short axis to less than (<) 10 millimeter (mm). Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Any radiological assessments taken more than 30 days after the last dose of study therapy or after antineoplastic agents other than study treatments taken by the participants was excluded from the best overall response derivation. Confirmation of CR or PR was to be at least 4 weeks apart from the previous radiological assessment.
Measured: From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks)
Secondary outcomes (43)
Number of Participants With Dose Limiting Toxicities (DLTs) in Cycle 1: Part II
DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle (first 21 days for infigratinib and capmatinib; 28 days for ribociclib and buparlisib) of treatment initiation and met the defined criteria for study.
Measured: Cycle 1 (21 days following the first dose of the combination treatment with buparlisib and capmatinib; 28 days for the combination with ribociclib and infigratinib)
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Part I
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs.
Measured: Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With AEs and SAEs: Part II
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs.
Measured: Day 1 up to 30 days after last dose (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Parameters evaluated were: Activated partial thromboplastin time (APTT) (seconds [sec]) - CTCAE graded high, fibrinogen (gram per liter [g/L]) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, prothrombin international normalized ratio (PINR) - CTCAE graded high, lymphocytes (10^9 cells/L) - CTCAE graded low, lymphocytes (10^9 cells/L) - CTCAE graded high, neutrophils (10^9 cells/L) - CTCAE graded low, platelets (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment.
Measured: Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Parameters evaluated were: APTT (sec) - CTCAE graded high, fibrinogen (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, PINR - CTCAE graded high, lymphocytes (10^9 cells/L) - CTCAE graded low, lymphocytes (10^9 cells/L) - CTCAE graded high, neutrophils (10^9 cells/L) - CTCAE graded low, platelets (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment in Part II.
Measured: Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (units per liter [U/L])- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (micromole per liter [umol/L])- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (millimole per liter [mmol/L])- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher.
Measured: Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (U/L)- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L) - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (umol/L)- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (mmol/L)- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher.
Measured: Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Vital signs evaluated were: Low/high systolic blood pressure (BP) (millimeter of Mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of >=20 mmHg / >=160 mmHg with increase from baseline of >=20 mmHg; low/high diastolic BP [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg / >=100 mmHg with increase from baseline of >=15 mmHg; low/high pulse rate (beats per minute [bpm]): <=50 bpm with decrease from baseline of >=15 bpm / >=120 bpm with increase from baseline of >=15 bpm; low/high weight (kilogram [kg]): >=20% decrease/increase from baseline; and low/high body temperature (degree Celsius [C]): <=36 C / >= 37.5 C.
Measured: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Vital signs evaluated were: Low/high systolic BP (mmHg): <=90 mmHg with decrease from baseline of >=20 mmHg / >=160 mmHg with increase from baseline of >=20 mmHg; low/high diastolic BP [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg / >=100 mmHg with increase from baseline of >=15 mmHg; low/high pulse rate (bpm): <=50 bpm with decrease from baseline of >=15 bpm / >=120 bpm with increase from baseline of >=15 bpm; low/high weight (kg): >=20% decrease/increase from baseline; and low/high body temperature (C): <=36 C / >= 37.5 C.
Measured: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: Heart rate (HR): increase from baseline >25% and to a value >100 bpm, decrease from baseline >25% and to a value <60 bpm; PR: increase from baseline >25% and to a value >200 millisecond (ms); QRS: increase from baseline >25% and to a value >110 ms; QT: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms; and Corrected QT interval by Fridericia (QTcF): increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms. New = newly occurred post-baseline value.
Measured: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Notable ECG Values: Part II
Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: HR: increase from baseline >25% and to a value >100 bpm, decrease from baseline >25% and to a value <60 bpm; PR: increase from baseline >25% and to a value >200 ms; QRS: increase from baseline >25% and to a value >110 ms; QT: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms; and QTcF: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms. New = newly occurred post-baseline value.
Measured: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With At Least One Dose Interruption: Part I
In this outcome measure number of participants with at least 1 dose interruption for encorafenib and binimetinib were reported.
Measured: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With At Least One Dose Interruption: Part II
In this outcome measure number of participants with at least 1 dose interruption for encorafenib, binimetinib, and each third combination agent were reported.
Measured: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With At Least One Dose Reduction: Part I
In this outcome measure number of participants with at least 1 dose reduction for encorafenib and binimetinib were reported.
Measured: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With At Least One Dose Reduction: Part II
In this outcome measure number of participants with at least 1 dose reduction for encorafenib, binimetinib, and each third combination agent were reported.
Measured: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Actual Dose Intensity: Part I
Dose intensity across all cycles = cumulative dose/duration of exposure. Treatment cycle for encorafenib and binimetinib =21 days.
Measured: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Actual Dose Intensity: Part II
Dose intensity = cumulative dose/ duration of exposure. Treatment cycle = 21days for the combination treatment with buparlisib and capmatinib and 28 days for the combination treatment with ribociclib and infigratinib.
Measured: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Progression-Free Survival (PFS): Part I
PFS was defined as the time from the start date of study drug in Part I until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. 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. Kaplan Meier method used for estimation.
Measured: From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part I was 403.7 weeks)
PFS: Part II
PFS was defined as the time from the start date of study drug in Part II until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. 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. Kaplan Meier method used for estimation.
Measured: From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks)
Duration of Response (DOR): Part I
DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in 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, sum must also demonstrate an absolute increase of at least 5 mm.
Measured: From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part I was 403.7 weeks)
DOR: Part II
DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in 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, sum must also demonstrate an absolute increase of at least 5 mm.
Measured: From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part II was 97.0 weeks)
Time to Response (TTR): Part I
TTR was defined as the time between the start date of study drug in Part I and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation.
Measured: From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part I was 403.7 weeks)
TTR: Part II
TTR was defined as the time between the start date of study drug in Part II and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation.
Measured: From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part II was 97.0 weeks)
Disease Control Rate (DCR): Part I
DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. 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.
Measured: From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part I was 403.7 weeks)
DCR: Part II
DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. 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.
Measured: From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part II was 97.0 weeks)
Overall Survival (OS): Part II
OS was defined as the time from the start date of study treatment (3rd agent combined with encorafenib and binimetinib) 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 known date participant alive. Kaplan Meier method used for estimation.
Measured: From date of start of treatment to date of death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks)
Summary of Genomic Biomarkers From Tumor Samples: Part I
Number of participants with multiple alterations in genomic biomarkers like biomarker BRAF, CCND1, CDK4, EGFR, FGFR1, FGFR4, KRAS, MET, NRAS, PIK3CA, and PTEN were reported and alterations included copy number variant/copy number ratio (CNV/CNR), rearrangement, short variant. It was not necessary that all biomarkers had all alterations. Baseline = last non-missing value prior to the first dose of study treatment.
Measured: Baseline up to end of treatment (EOT) (maximum treatment exposure for Part I was 403.7 weeks)
Plasma Concentration for Encorafenib (LGX): Part I
In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5) and end of treatment (EOT). Maximum treatment exposure for Part I was of 403.7 weeks.
Measured: C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT
Plasma Concentration for Encorafenib (LGX): Part II
In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 16 (D16), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5). Maximum treatment exposure for Part II was of 97.0 weeks.
Measured: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part I was of 403.7 weeks.
Measured: C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part II was of 97.0 weeks.
Measured: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
LEQ803 is metabolite of ribociclib. Maximum treatment exposure for Part II was of 97.0 weeks.
Measured: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
BHS697 and CQM157 are metabolites of infigratinib. Maximum treatment exposure for Part II was of 97.0 weeks.
Measured: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; EOT
Plasma Concentration for Capmatinib (INC): Part II
Maximum treatment exposure for Part II was of 97.0 weeks.
Measured: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Buparlisib (BKM): Part II
Maximum treatment exposure for Part II was of 97.0 weeks.
Measured: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Measured: C1 D15: 0.5 hour ± 10 (minutes) min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Measured: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Measured: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Elimination half-life means the time required for the plasma concentration to decline by 50% during the elimination phase.
Measured: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Measured: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution is the apparent volume of distribution at steady-state.
Measured: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Measured: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Measured: C1 D15: at the end of a dosing interval at steady-state (24 hour ± 2 hour), taken directly before next administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2014 (estimated)
- Study start23 Jul 2014
- Primary completion10 Jan 2023
- Study completion10 Jan 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 (2)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02159066
- Sponsor's protocol ID
- CLGX818X2109
- Other IDs
- C4221013, 2013-004552-38
- Acronym
- LOGIC-2
- Status last verified
- Feb 2024
- First submitted
- 28 Apr 2014
- Last updated
- 5 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
Dummer R, Sandhu S, Miller WH Jr, Butler MO, Taylor MH, Heinzerling L, Blank CU, Couselo EM, Burris HA 3rd, Postow MA, Chmielowski B, Middleton MR, Berking C, Hassel JC, Gesierich AH, Mauch C, Kleha JF, Polli A, Harney AS, di Pietro A, Ascierto PA. Plain language summary of the LOGIC 2 study: Encorafenib, binimetinib, plus a third drug for people with BRAF V600-mutant melanoma. Future Oncol. 2026 Apr;22(9):995-1013. doi: 10.1080/14796694.2026.2643481. Epub 2026 Mar 31.
PubMed 41914670Nassar KW, Hintzsche JD, Bagby SM, Espinoza V, Langouet-Astrie C, Amato CM, Chimed TS, Fujita M, Robinson W, Tan AC, Schweppe RE. Targeting CDK4/6 Represents a Therapeutic Vulnerability in Acquired BRAF/MEK Inhibitor-Resistant Melanoma. Mol Cancer Ther. 2021 Oct;20(10):2049-2060. doi: 10.1158/1535-7163.MCT-20-1126. Epub 2021 Aug 10.
PubMed 34376578
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The LOGIC 2 Trial A Phase II, Multi-center, Open-label Study of Sequential LGX818/MEK162 Combination Followed by a Rational Combination With Targeted Agents After Progression, to Overcome Resistance in Adult Patients With Locally Advanced or Metastatic BRAF V600 Melanoma.
- ClinicalTrials.gov ID
- NCT02159066
- Acronym / sponsor ID
- LOGIC-2 / CLGX818X2109
- Conditions
- Melanoma
- Keywords
- Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 23 Jul 2014 (actual)
- Primary completion
- 10 Jan 2023 (actual)
- Study completion
- 10 Jan 2023 (actual)
- First posted
- 9 Jun 2014 (estimated)
- Results
- Posted 5 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations.
Detailed description
This study consists of two parts: in Part I/Run-In, patients naïve to selective BRAF and MEK inhibitors will be treated with the LGX818/MEK162 combination until disease progression (as defined per RECIST v1.1). Based on the genetic analysis of a tumor biopsy obtained at that time, patients will enter Part II of the study for tailored combination treatment in one of four arms of LGX818/MEK162 + either BKM120, BGJ398, INC280 or LEE011 Patients with BRAF mutant melanoma treated by LGX818/MEK162 combination in other studies can be enrolled directly in Part II of CLGX818X2109 after relapse.
Dose-escalations in the combination arms for which no MTD has been established will be based on the recommendations of a Bayesian logistic regression model guided by an escalation with overdose control criterion
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| LGX818 + MEK162 | Experimental | Drug: LGX818, Drug: MEK162 |
| LGX818 + MEK162 + LEE011 | Experimental | Drug: LEE011 |
| LGX818 + MEK162 + BGJ398 | Experimental | Drug: BGJ398 |
| LGX818 + MEK162 + BKM120 | Experimental | Drug: BKM120 |
| LGX818 + MEK162 + INC280 | Experimental | Drug: INC280 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (41 listed)
- Age ≥ 18 years
- Histologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IIIC to IV per American Joint Committee on Cancer [AJCC])
- Documented evidence of BRAF V600 mutation.
- Newly obtained tumor biopsy at baseline, and patient agrees to a mandatory biopsy at the time of progression, if not medically contraindicated.
- Evidence of measurable disease, as determined by RECIST v1.1.
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| LGX818Combination of LGX818 and MEK162 (Part I) | Drug | LGX818 + MEK162 |
| MEK162Combination of LGX818 and MEK162 (Part I) | Drug | LGX818 + MEK162 |
| LEE011Combination of LGX818 + MEK162 + LEE011 (Part II) | Drug | LGX818 + MEK162 + LEE011 |
| BGJ398Combination of LGX818 + MEK162 + BGJ398 (Part II) | Drug | LGX818 + MEK162 + BGJ398 |
| BKM120Combination of LGX818 + MEK162 + BKM120 (Part II) | Drug | LGX818 + MEK162 + BKM120 |
| INC280Combination of LGX818 + MEK162 + INC280 (Part II) | Drug | LGX818 + MEK162 + INC280 |
Primary outcome
Overall Response Rate (ORR): Part II
Time frame: From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks)
ORR: percentage of participants with confirmed complete response (CR) and partial response (PR). Response evaluation criteria in solid tumors (RECIST) v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions that had a reduction in short axis to less than (<) 10 millimeter (mm). Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Any radiological assessments taken more than 30 days after the last dose of study therapy or after antineoplastic agents other than study treatments taken by the participants was excluded from the best overall response derivation. Confirmation of CR or PR was to be at least 4 weeks apart from the previous radiological assessment.
43 secondary outcomes
Number of Participants With Dose Limiting Toxicities (DLTs) in Cycle 1: Part II
Time frame: Cycle 1 (21 days following the first dose of the combination treatment with buparlisib and capmatinib; 28 days for the combination with ribociclib and infigratinib)
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Part I
Time frame: Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With AEs and SAEs: Part II
Time frame: Day 1 up to 30 days after last dose (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I
Time frame: Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II
Time frame: Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I
Time frame: Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II
Time frame: Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I
Time frame: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II
Time frame: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With Notable Electrocardiograms (ECG) Values: Part I
Time frame: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With Notable ECG Values: Part II
Time frame: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With At Least One Dose Interruption: Part I
Time frame: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With At Least One Dose Interruption: Part II
Time frame: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Number of Participants With At Least One Dose Reduction: Part I
Time frame: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Number of Participants With At Least One Dose Reduction: Part II
Time frame: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Actual Dose Intensity: Part I
Time frame: During study treatment (maximum treatment exposure for Part I was 403.7 weeks)
Actual Dose Intensity: Part II
Time frame: During study treatment (maximum treatment exposure for Part II was 97.0 weeks)
Progression-Free Survival (PFS): Part I
Time frame: From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part I was 403.7 weeks)
PFS: Part II
Time frame: From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks)
Duration of Response (DOR): Part I
Time frame: From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part I was 403.7 weeks)
DOR: Part II
Time frame: From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part II was 97.0 weeks)
Time to Response (TTR): Part I
Time frame: From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part I was 403.7 weeks)
TTR: Part II
Time frame: From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part II was 97.0 weeks)
Disease Control Rate (DCR): Part I
Time frame: From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part I was 403.7 weeks)
DCR: Part II
Time frame: From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part II was 97.0 weeks)
Overall Survival (OS): Part II
Time frame: From date of start of treatment to date of death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks)
Summary of Genomic Biomarkers From Tumor Samples: Part I
Time frame: Baseline up to end of treatment (EOT) (maximum treatment exposure for Part I was 403.7 weeks)
Plasma Concentration for Encorafenib (LGX): Part I
Time frame: C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT
Plasma Concentration for Encorafenib (LGX): Part II
Time frame: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I
Time frame: C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT
Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II
Time frame: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II
Time frame: C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II
Time frame: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; EOT
Plasma Concentration for Capmatinib (INC): Part II
Time frame: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Plasma Concentration for Buparlisib (BKM): Part II
Time frame: C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Time frame: C1 D15: 0.5 hour ± 10 (minutes) min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II
Time frame: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Time frame: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II
Time frame: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II
Time frame: C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41914670Dummer R, Sandhu S, Miller WH Jr, Butler MO, Taylor MH, Heinzerling L, Blank CU, Couselo EM, Burris HA 3rd, Postow MA, Chmielowski B, Middleton MR, Berking C, Hassel JC, Gesierich AH, Mauch C, Kleha JF, Polli A, Harney AS, di Pietro A, Ascierto PA. Plain language summary of the LOGIC 2 study: Encorafenib, binimetinib, plus a third drug for people with BRAF V600-mutant melanoma. Future Oncol. 2026 Apr;22(9):995-1013. doi: 10.1080/14796694.2026.2643481. Epub 2026 Mar 31.
- Derived from this study: PubMed 34376578Nassar KW, Hintzsche JD, Bagby SM, Espinoza V, Langouet-Astrie C, Amato CM, Chimed TS, Fujita M, Robinson W, Tan AC, Schweppe RE. Targeting CDK4/6 Represents a Therapeutic Vulnerability in Acquired BRAF/MEK Inhibitor-Resistant Melanoma. Mol Cancer Ther. 2021 Oct;20(10):2049-2060. doi: 10.1158/1535-7163.MCT-20-1126. Epub 2021 Aug 10.
- 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.
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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 CT.gov Call Center study director
Pfizer
32 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LGX818, MEK162 and LEE011 in people with Melanoma, run by Pfizer at 32 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 41 inclusion and 0 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 5 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 32 sites in United States, Germany, Australia, Canada, Italy 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 phase mean?
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 5 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?
Overall Response Rate (ORR): Part II (time frame: From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks)). 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 NCT02159066, which also lists 2 linked publications.
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 5 Mar 2024.