Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication MEKTOVI is a kinase inhibitor indicated: • in combination with encorafenib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. FDA label
Also known as MEK162, Binimetinib Oral, Mektovi, ARRY-162
binimetinib · 11 trials · 15 indications
PFS: time from randomization to first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD: \>=20% increase in sum of diameter of target lesions (TLs) taking as reference the smallest sum on study (including baseline sum), sum must also be an absolute increase of \>=5 mm; unequivocal progression of existing non-TLs; appearance of \>=1 lesion. Complete response (CR): disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs. Partial response (PR): \>=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor increase in lesions qualified for PD referring smallest sum diameter. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS censored at date of last adequate tumor assessment of CR, PR or SD.
Defined as complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The ORR at stages 1 and 2 will be estimated using the method of Whitehead, and the p-values for testing the null hypothesis at each stage will use the method of Koyama \& Chen and 90% confidence interval will be reported.
DLT:Adverse event(AE)/abnormal laboratory assessed unrelated-disease,disease progression,intercurrent illness/concomitant medication/therapies resulting inability tolerate 75% dose intensity in Cycle 1.Total bilirubin(TBL)grade(G)\>=3 (\>3.0\*upper limit of normal\[ULN)\]);AST/ALT\>5-8\*ULN\>5 days,\>8\*ULN,\>3\*ULN concurrent TBL\>2\*ULN;G\>=3 serum creatinine,CK elevation,ECG QTcF prolonged,G3 troponin,electrolyte\>72 hours,G3/4 amylase/lipase.G4 ANC,platelet count\>7 days;G3/4 platelet count,other AE except lymphopenia.G\>=3 retinopathy,other disorder\>21 days;G2 uveitis/eye pain/blurred vision/decreased visual acuity;G4 other disorder.Decrease LVEF\>10% G\>=3 cardiac disorders.G3/4 hypertension.G3 fatigue\>=7 days,hypersensitivity,infusion reaction,fever\>=72 hours/hemodynamic compromise,endocrinopathy.G\>=2 interstitial lung disease/pneumonitis;G3 bronchospasm.G3/4 rash,hand foot skin reaction,photosensitivity.G3 colitis;G3/4 diarrhea,nausea/vomiting.Neurologic G3.Other hematologic/nonhematolic G\>=3 AE.
ORR was defined as the percentage of participants who achieved a best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator per RECIST v1.1. As per RECIST v1.1, CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<)10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was considered progression.
CBR: participants with complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks. As per RECIST 1.1, CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to less than (\<) 10 millimeter (mm); PR: at least a 30 percent (%) decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of \>=1 new target or non-target lesions.
CBR: participants with stringent complete response(sCR), CR, very good partial response(VGPR), PR/SD for at least 16 weeks. For hematologic tumors (multiple myeloma), sCR: negative immunofixation on serum, urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow plus normal free light chain(FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry/immunofluorescence; CR: negative immunofixation on the serum, urine, disappearance of any soft tissue, plasmacytomas and \<5% plasma cells in bone marrow; VGPR: serum,urine M-component detectable by immunofixation but not on electrophoresis or\>=90% reduction in serum M-component plus urine M-component \<100 mg/24 hr; PR: \>50% reduction of serum M-protein and reduction in 24hr urinary M-protein by \>90%/to \<200 mg/24 hr; SD: not meeting criteria for CR, VGPR, PRor PD; PD: increase of \>25% from lowest response value in serum M-component, urine M-component and bone marrow plasma cell percentage.
CBR: participants with complete remission (CR), CR with incomplete blood count recovery (CRi), partial remission (PR) and no resposne for at least 16 weeks. For hematologic tumors (acute myeloid leukemia); CR: as bone marrow- \< 5% blasts, no blasts with auer rods, peripheral blood- neutrophils ≥1.0\*10\^9/L and/or platelets ≥100\*10\^9/L, ≤1% blasts, no evidence of extramedullary disease (such as CNS or soft tissue involvement), transfusion independent; CRi: all the CR criteria were involved but platelet and neutrophil transfusions were also allowed; PR: bone marrow- 50% or greater decrease (absolute range 5-25% blasts), \< 5% of blasts contain auer rods, peripheral blood- neutrophils \<1.0\*10\^9/L and/or platelets \<100\*10\^9/L, no evidence of extramedullary disease; no response: in case a patient did not achieve CR, CRi, PR or relapse for an individual response assessment.
Objective response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.0, was defined as participants with a best overall response of complete response (CR) or partial response (PR), were recorded from date of randomization or date of start of treatment until date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target and non-target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
DLT was defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment (Cycle 1) with binimetinib and panitumumab and met any of the specified criteria.
ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to \<10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
To estimate the maximum tolerate doses (MTDs) and/or identify the RP2D and schedule of LEE011 and MEK162 combination. A dose-limiting toxicity (DLT) was defined as an AE or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle of treatment with ribociclib and binimetinib.
ORR is the proportion of patients with best overall response of complete response (CR) or partial response (PR) by month 2 assessed according to RECIST 1.1 criteria. ORR is done to describe the anti-tumor activity of LEE011 and MEK162 combination. The primary analysis of the ORR was based on the Investigator's assessment of overall lesion responses per RECIST 1.1.
Incidence of frequency of Dose limiting toxicities during first 4 weeks will be measured according to the commen terminology criteria for adverse events (CTCAE).
| Arm | Type | Description |
|---|---|---|
| MEK162 | EXPERIMENTAL | - |
| Dacarbazine | ACTIVE_COMPARATOR | - |
| Treatment (binimetinib, imatinib) | EXPERIMENTAL | Patients receive binimetinib PO BID on days 1-28 and imatinib PO QD on days 1-28. Cycles repeat every 28 days |
| Phase 1b / Arm 1A | EXPERIMENTAL | binimetinib + nivolumab |
| Phase 1b / Arm 1B | EXPERIMENTAL | binimetinib + nivolumab + ipilimumab |
| Phase 2 / Arm 2A | EXPERIMENTAL | binimetinib + nivolumab |
| Phase 2 / Arm 2B | EXPERIMENTAL | binimetinib + nivolumab + ipilimumab |
| BRAFV600 mutant, 45mg bid MEK162 | EXPERIMENTAL | BRAFV600 mutant, 45mg bid MEK162 |
| NRAS mutant, 45mg bid MEK162 | EXPERIMENTAL | NRAS mutant, 45mg bid MEK162 |
| BRAFV600 mutant, 60mg bid MEK162 | EXPERIMENTAL | BRAFV600 mutant, 60mg bid MEK162 |
| MEK162 and mFOLFIRI, all patients | EXPERIMENTAL | - |
| Phase Ib: Dose escalation | EXPERIMENTAL | Phase Ib: Dose escalation. |
| Phase II: Patients with mutant RAS mCRC | EXPERIMENTAL | Patients with mutant RAS mCRC who have not been pretreated with an EGFR inhibitor (EGFRi), including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
| Phase II: Patients with acquired mutant RAS mCRC | EXPERIMENTAL | Patients with acquired mutant RAS mCRC who have been pretreated with anti-EGFR monoclonal antibody therapy, but have not been pre-treated with EGFR tyrosine kinase inhibitor therapy. |
| Phase II: Patients with WT RAS mCRC (pretreated) | EXPERIMENTAL | Patients with WT RAS mCRC who have been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
| Phase II: Patients with WT RAS mCRC (not pretreated) | EXPERIMENTAL | Patients with WT RAS mCRC who have not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
| Phase Ib | EXPERIMENTAL | The phase Ib is the dose escalation part where successive cohorts of 3-6 newly enrolled patients receiving various dose pairs considering the recommendation from an adaptive BLRM incorporating the EWOC principle until MTD(s)/RP2D is defined. If multiple alternate dosing schedules are explored in parallel, the allocation of patients will proceed in an alternating fashion. Approximately 40 patients are expected to be treated during the phase Ib part of the study. Dosing Schedule 1: MEK162 administered orally twice daily on a continuous dosing schedule. LEE011 administered orally once daily for 21 days followed by a 1 week break (28-day cycle). Dosing Schedule 2: MEK162 administered orally twice daily and LEE011 administered orally once daily for 3 weeks followed by a 1 week break (28-day cycle). Dosing Schedule 3: MEK162 administered orally twice daily and LEE011 administered once daily for 2 weeks followed by a 1 week break (21-day cycle). |
| Phase II | EXPERIMENTAL | The Phase II part will begin once the MTD(s)/RP2D have been determined in the Phase Ib in order to assess antitumor activity of the LEE011and MEK162 combination. Patients enrolled in the Phase II part of the study are required to have measurable disease. Approximately 40 patients will be treated in this part. Phase II part will begin at the RP2D on the chosen schedule in order to assess antitumor activity of the LEE011 and MEK162 combination. |
| MEK162 + paclitaxel | EXPERIMENTAL | - |
| MEK162 + RAF265 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| MEK162 | DRUG | MEK162 will be administered as a fixed dose of 45 mg (3 x 15 mg tablets) BID, with a glass of water and taken with or without food. |
| Dacarbazine | DRUG | Patients randomized to dacarbazine will receive an IV infusion of dacarbazine 1000 mg/m2 over the course of 1 hour on day 1 and then every three weeks. |
| Binimetinib | DRUG | Taken orally (PO) twice a day (BID) |
| Imatinib | DRUG | Taken orally (PO) once a day (QD) |
| nivolumab | DRUG | Intravenously (IV) every 4 weeks (Q4W) |
| ipilimumab | DRUG | intravenously (IV) every 8 weeks (Q8W) |
| MEK162 and mFOLFIRI | DRUG | MEK162 in combination with mFOLFIRI in a 14 day cycle MEK162 will be given single agent 6 day lead in and then will be given in combination with mFOLFIRI mFOLFIRI Administered Day 1 of each cycle Irinotecan 180mg/m2 iv over 90 minutes on day 1 5-fluoruracil 1200mg/m2 continuous infusion for 48 hours (2400mg/m2 in 48 hours) Followed by MEK162 - Taken twice daily orally on Days 1-12 of each cycle Level -1: mFOLFIRI at 80% + MEK162 30 mg twice daily 1 week on and 1 week off Level 1: mFOLFIRI + MEK162 30 mg twice daily Level 2: mFOLFIRI + MEK162 45 mg twice daily |
| Panitumumab | DRUG | Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle) |
| LEE011 | DRUG | LEE011 will be administered orally once daily |
| MEK162, MEK inhibitor; oral | DRUG | multiple dose, escalating |
| Paclitaxel, mitotic inhibitor; intravenous | DRUG | multiple dose, single schedule |
| MEK162 + RAF265 | DRUG | - |
Inclusion Criteria: * Diagnosis of locally advanced, unresectable or metastatic cutaneous or melanoma of unknown primary AJCC Stage IIIC or IV (uveal and mucosal melanoma are excluded) * Presence of NRAS Q61 mutation in tumor tissue prior to randomization as determined by a Novartis designated cent...
Binimetinib is an oral small molecule cancer therapy being studied in solid tumors and metastatic melanoma. It is also known as MEK162. Binimetinib is being developed by Pfizer, Inc. (ticker: PFE) and is currently in Phase 1 clinical development. It is an investigational agent and has not been approved by the FDA.
Binimetinib targets MAP2K1 and MAP2K2, also known as MEK1 and MEK2. It is classified as a MEK inhibitor. By inhibiting these kinases, binimetinib is designed to block signaling through the MAPK pathway, which is often activated in tumors with BRAF or RAS mutations.
Binimetinib is being developed by Pfizer, Inc., which trades under the ticker PFE. Pfizer is the company associated with the clinical development program for binimetinib, also known as MEK162.
Binimetinib is in Phase 1 clinical development. It is an investigational drug and is not FDA approved. The Phase 1 designation reflects the earliest stage of human testing, though individual studies of binimetinib have been conducted at Phase 1 and Phase 2 levels.
Binimetinib has been studied in trials including NCT04598009, a Phase 2 study of binimetinib plus imatinib in KIT-mutant melanoma, and NCT03271047, a Phase 2 study in microsatellite-stable RAS-mutant colorectal cancer. Earlier studies include NCT02613650 and NCT01927341 in RAS-positive metastatic colorectal cancer.
Yes, binimetinib is also known as MEK162. MEK162 is an alternative name used for the same investigational compound. Other names associated with binimetinib include MEK inhibitor and combinations such as MEK162 plus RAF265 and MEK162 with mFOLFIRI.