Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Binimetinib, binimetinib
MEK162 · 5 trials · 5 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.
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.
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 | - |
| 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 |
| 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. |
| 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. |
| Panitumumab | DRUG | Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle) |
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 investigational small molecule kinase inhibitor being studied in oncology. It is being evaluated for epithelial ovarian cancer, advanced solid tumors, metastatic colorectal cancer, advanced KRAS positive metastatic colorectal cancer, BRAF or NRAS mutant metastatic melanoma, and melanoma stage III. It is currently in Phase 2 clinical development.
Binimetinib is a kinase inhibitor, belonging to the -tinib class of drugs. It targets MEK, a kinase in the RAS/RAF/MEK/ERK pathway. By inhibiting MEK, it is designed to block signaling that drives tumor growth in cancers with RAS or BRAF mutations.
Binimetinib is being developed by Pfizer, Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol PFE. The drug is currently in Phase 2 clinical trials for multiple oncology indications.
Binimetinib is currently in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. It is being studied across multiple oncology indications, including advanced solid tumors and metastatic colorectal cancer.
Binimetinib has been studied in several clinical trials. NCT01352273 was a Phase 1 trial in advanced solid tumors with RAS or BRAFV600E mutations. NCT01649336 was a Phase 1 trial in ovarian, fallopian tube, or peritoneal cancer. NCT01763164 was a Phase 3 trial in NRAS-mutant melanoma. NCT03271047 is a Phase 2 trial in MSS, RAS-mutant colorectal cancer.
Yes, Binimetinib is also known as MEK162. Clinical trials such as NCT01352273 and NCT01649336 refer to the drug as MEK162. This alternative name is used in research settings and historical trial documentation.