Approval was based on a ninecohort, nonrandomized trial. Highlights of prescribing information cardiomyopathy. Full text mechanisms of resistance to braf and mek. Mekinist trametinib tablets, for oral use initial u. Aug 25, 2015 phase ii studies of trametinib in monotherapy and in combination. Full prescribing information is available, including clinical trial information, safety, dosing, drugdrug interactions and contraindications on may 29, 20, the food and drug administration fda approved trametinib mekinist tablet, glaxosmithkline, llc, for the treatment of. Full title an openlabel, doseescalation, phase iii study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of the mek inhibitor trametinib in children and adolescents subjects with cancer or plexiform neurofibromas and trametinib in combination with dabrafenib in children and adolescents with cancers harboring v600 mutation purpose the purpose of this study. Trametinib is the first fdaapproved mek12 inhibitor, approved may 29, 20, for the treatment of braf v600ek melanoma. Trametinib mekinist is a reversible and highly selective allosteric inhibitor of mek1 and mek2 with anticancer activity against metastatic melanoma carrying the braf v600 mutation. Fda approves dabrafenib plus trametinib for adjuvant treatment of. Trametinib is used alone or in combination with another medicine called dabrafenib tafinlar. As soon as possible, but no later than 14 days from the date of this letter, submit the content of labeling 21 cfr 314.
Trametinib in treating patients with advanced cancer with or. Food and drug administration fda approved trametinib mekinist tablets, glaxosmithkline, usa, as a single agent oral treatment for patients with nonoperable melanoma melanoma that cannot be removed by surgery or metastatic melanoma melanoma which has spread to other parts of the body with braf v600e or v600k mutations as detected by an fda. However, this drug is also proposed in phase ii for brain metastases from melanoma, and other solid tumours, such as colorectal cancer and nonsmall cell lung cancer. On may 29, 20, the food and drug administration fda approved trametinib mekinist tablet, glaxosmithkline, llc, for the treatment of patients. Trametinib also known as gsk1120212 or jtp 74057, originally identified as a p15 inductive compound, is a novel and potent allosteric inhibitor of mek kinase, which exhibits atp noncompetitive inhibition against mek1 and mek2 kinase. Trametinib monotherapy has not demonstrated clinical activity in patients who have progressed on a prior braf inhibitor therapy see section 5. Ncis basic information about clinical trials explains the types and phases of trials and how they are carried out. Trametinib mekinist is a second generation, allosteric smallmolecule inhibitor of mek12. This draft guidance, when finalized, will represent the.
Trametinib is a thirdgeneration, orally available, highly selective allosteric atp noncompetitive inhibitor of the 2 isoforms of mitogenactivated extracellular signalregulated kinase 1 mek1 and mek2. Trametinib had good results for metastatic melanoma carrying the braf v600e mutation in a phase iii clinical trial. Oncolytic hsv therapy increases trametinib access to brain. Australian public assessment report for trametinib as. Mekinist trametinib dose, indications, adverse effects. Fiveyear outcomes with dabrafenib plus trametinib in metastatic melanoma. List of drug master files dmf of trametinib active pharmaceutical ingredient api submitted to the u. Clinical activity of trametinib in unresectable, braf v600 mutationpositive melanoma was observed in phase 1, 2 and 3 studies 35. Mekinist trametinib or cotellic cobimetinib in combination with. Fda approves combination of trametinib and dabrafenib for. Trametinib api dmfs us drug master file dmf details. Mekinist as a single agent is indicated for the treatment of patients with unresectable or metastatic melanoma with braf v600e or v600k mutations, as detected by an fda approved.
Key clinicaltrial evidence for trametinib dermnet nz. Suitably, trametinib is in the form of a dimethyl sulfoxide solvate. Fda approves dabrafenib plus trametinib for anaplastic thyroid. Dabrafenib in combination with trametinib in the treatment. A phase iii study of trametinib in children and adolescents. Trametinib is a reversible, highly selective allosteric inhibitor of mek1mek2 activation and kinase activity 1,2 which has been approved in the united states for the treatment of braf v600e or v600k mutationpositive melanoma. The content of this database of side effects adverse drug reactions is intended for educational and scientific research purposes only. The fda also approved the first nextgeneration sequencing oncology panel test for.
Content of premarket submissions for software contained in. Melanoma, metastatic, nonsmall cell lung cancer, thyroid cancer mekinist trametinib is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with braf v600e or v600k. Mekinist is a drug marketed by novartis and is included in one nda. Submission of software programs to fda submission of software programs to regulatory agencies submission of software programs to regulatory agencies 7. Nov 09, 2018 trametinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body.
Keep taking trametinib as you have been told by your doctor or other health care provider, even if you feel well. Trametinib in treating patients with advanced cancer with. This prior approval supplemental new drug application provides for updates to the. The basics on adverse event monitoring, assessment and. Clinical trials using trametinib national cancer institute. Nov 14, 2019 use trametinib as ordered by your doctor. Trametinib is used alone or in combination with dabrafenib to treat melanoma skin cancer that has spread or that cannot be removed by surgery. Trametinib activity has been evaluated in the treatment of variety of cancers, and is currently approved as a monotherapy for subjects with unresectable or metastatic melanoma with braf v600ek mutation. Trametinib inhibits the action of the abnormal braf protein, with the aim of slowing the growth and spread of the cancer.
Sorafenib, the only targeted therapeutic agent for hcc, is a multiple kinase inhibitor with targets including raf and vegfr23 that display a very limited ability to extend the survival of patients with advanced metastatic hcc for approximately three months. Combination therapy with braf and mek inhibitors for melanoma. Eu submission 32 extended use 1 fast track fda 66 fda 15 4 fda 2010 2 fda 2011 1 fda 2012 6 fda 20 6 fda 2014 52 fda 2015 39 fda 2016 23 fda 2017 58 fda 2018 53 fda 2019 41 fda 2020 6 featured product 1 female sexual dysfunction 1 flow synthesis 14 formulation 14 gain 1 generating antibiotic incentives. It preferentially binds unphosphorylated mek12, preventing rafdependent mek phosphorylation and activation 32,33. Mekinist trametinib is now approved for the treatment of adult patients with unresectable or metastatic melanoma with braf v600e and v600k mutations as detected by an fda approved test. Submission of software programs to regulatory agencies. Mekinist approved for unresectable or metastatic melanoma with braf v600e or v600k mutation full prescribing information is available, including clinical trial information, safety, dosing, drugdrug interactions and contraindications. Novartis said the european commission has approved tafinlardabrafenib in combination with mekinist trametinib for the treatment of patients with braf v600positive advanced or metastatic nonsmall cell lung cancer.
Expedited programs for serious conditionsdrugs and. Fda grants regular approval to dabrafenib and trametinib. For the treatment of unresectable or metastatic malignant melanoma in braf inhibitornaive patients with braf v600e or v600k mutations, as a single agent. Except as otherwise noted, this work is licensed under a creative commons attributionnoncommercialshare alike 4. Selumetinib approved by fda neurofibromatosis inspire. Dabrafenib in combination with trametinib in the treatment of. Listing a study does not mean it has been evaluated by the u. Approval was based on combiad nct01682083, an international, multicenter. It is a mek inhibitor drug with anticancer activity. Concomitant oral and intravenous pharmacokinetics of. It is used to treat melanoma, nonsmall cell lung cancer, and thyroid cancer. At present, two selective braf inhibitors dabrafenib and vemurafenib and one mek inhibitor trametinib are fdaapproved for treating stage iv braf v600emutated metastatic melanoma.
Mekinst as a single agent is indicated for the treatment of patients with unresectable or metastatic melanoma with braf v600e or v600k mutations, as detected by an fdaapproved test see clinical studies 14. In a study undertaken to determine the safety of dabrafenib with and without trametinib and ipilimumab at the doses of dabrafenib 100 mg bid, trametinib 1 mg qd and ipilimumab at the fda approved dose of 3 mgkg every 3 weeks for 4 doses, 2 out of 7 advanced melanoma patients developed grade 3 colitis complicated by perforation puzanov, 2015. Trametinib in combination with sorafenib in patients with advanced hepatocellular cancer the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Trametinib has been designated as an orphan drug for the treatment of stage iib to iv melanoma by the fda as a singleagent or in combination with dabrafenib. Apexbio trametinib gsk1120212mek1 and mek2 inhibitor. Clinical trials look at new ways to prevent, detect, or treat disease.
Guidance for the content of premarket submissions for. The compound specifically binds to mek1 and mek2, resulting in. Synergistic activity of mtorc12 kinase and mek inhibitors. Trametinib is an orally available mek inhibitor recently approved by food and drug administration fda for use in treating metastatic melanoma in patients with brafv600e and brafv600k mutations, based upon results of a clinical trial by flaherty et al. Maria dalton, glaxosmithkline, collegeville pa, usa. Tafinlar dabrafenib, in combination with trametinib, for the treatment of patients. Trametinib side effects, dosage, interactions drugs. May 10, 2017 trametinib can cause fetal harm when administered to a pregnant woman.
The mek inhibitors enhance the efficacy of sorafenib. Trametinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body. Trametinib in treating patients with advanced cancer with or without hepatic dysfunction the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Guidance for the content of premarket submissions for software contained in medical devices guidance for industry and fda staff may 2005. Talk with your health care provider about your risk for these cancers.
Fda and are still used exclusively by the agency to evaluate 100% of the electronic submissions it receives. Create adam datasets generate tables and figures for primary and secondary efficacy analyses. For commercial use or customized versions, please contact biobyte solutions gmbh disclaimer. In this mutation, the amino acid valine v at position 600 within the braf protein has become replaced by glutamic acid e making the mutant braf. Mekinist trametinib dosing, indications, interactions. Tafinlar, when used in combination with mekinist, may cause a type of skin cancer called cutaneous squamous cell carcinoma, keratoacanthoma, basal cell carcinoma, or melanoma. Longterm outcomes in patients with braf v600mutant metastatic melanoma who received dabrafenib combined with trametinib.
Hepatocellular carcinoma hcc is one of the most common malignant tumours worldwide and has a poor prognosis. Trametinib, a human prescription drug labeled by glaxosmithkline llc. A description of fda expedited programs is in the guidance for industry. Trametinib in combination with sorafenib in patients with. The fda recently approved trametinib, a firstinclass, oral mek inhibitor for patients with unresectable or metastatic melanoma with braf v600k mutations. The ndc code 01730848 is assigned to mekinist also known as. Dabrafenib is also fda approved as a combination therapy with trametinib for the treatment of patients with unresectable or metastatic melanoma with a braf v600ek mutation. Ji young yoo, jessica swanner, yoshihiro otani, mitra nair, flora park, yeshavanth banasavadisiddegowda, joseph liu, alena cristina jaimeramirez, bangxing hong, feng geng, deliang guo, darlene bystry, mitch phelphs, haroon quadri, tae jin lee, balveen kaur, oncolytic hsv therapy increases trametinib access to brain tumors and sensitizes them in vivo, neurooncology, volume 21. Trametinib with or without vemurafenib in braf mutated non. The labeling included below is the version at time of approval of the original. Expedited programs for serious conditionsdrugs and biologics. Food and drug administration 10903 new hampshire avenue silver spring, md 20993 1888infofda 18884636332 contact fda. Mekinist is not indicated for the treatment of patients who have received a prior braf inhibitor therapy. When do mekinist patents expire, and what generic alternatives are available.
Fda approves dabrafenib plus trametinib for anaplastic thyroid cancer with braf. In this mutation, the amino acid valine v at position 600 within the braf protein has become. Trametinib is a medicine that targets proteins in cancer cells and stops the cancer cells from growing. Mek1583 was an openlabel, multicenter phase ii study investigating the objective response rate, safety, and pharmacokinetics of trametinib 2. Fda label information for this drug is available at dailymed. Ae reporting for ind studies significant updates to ind regs published in federal register 92910 new regs in effect 32811 important implications for sponsors and investigators 9 final rule on ind safety reporting see 22010. The clinical trials on this list are studying trametinib. Trametinib in combination with dabrafenib for treating. Contains nonbinding recommendations draft guidance on trametinib dimethyl sulfoxide recommended jan 2016 this draft guidance, when finalized, will represent the current thinking of the food and drug. The product monograph will be reissued in the event of serious. The approvals of dabrafenib and trametinib, administered concurrently, provide a new. Mekinist, in combination with dabrafenib, is indicated for the treatment of patients with unresectable or metastatic melanoma with braf v600e or v600k mutations, as detected by an fda approved test. Adverse drug reaction reporting and reissuance of the product monograph health care providers are encouraged to report adverse drug reactions associated with normal use of these and all drug products to health canadas canada vigilance program at 18662342345.
Guidance for the content of premarket submissions for software contained in medical devices. A description of fda expedited programs is available in the guidance for industry. Mekinist is also indicated, in combination with dabrafenib tafinlar, for. It is only used if the melanoma cells have the braf v600e or v600k mutations. Trametinib is also used together with dabrafenib to treat nonsmall cell. It is a mek inhibitor drug with anticancer activity it inhibits mek1 and mek2 trametinib had good results for metastatic melanoma carrying the braf v600e mutation in a phase iii clinical trial. Comparative evaluation of the new fda approved thxidbraf. Trametinib was embryotoxic and abortifacient in rabbits at doses greater than or equal to those resulting in exposures 0. Food and drug administration fda approved trametinib mekinist tablets, glaxosmithkline, usa, as a single agent oral treatment for patients with nonoperable melanoma melanoma that cannot be removed by surgery or metastatic melanoma melanoma which has spread to other parts of the body with braf v600e or v600k mutations as detected by an. Mechanisms of resistance to braf and mek inhibitors and clinical update of us food and drug administrationapproved targeted therapy in advanced melanoma sunilkumar kakadia,1 naveen yarlagadda,1 ramez awad,2 madappa kundranda,3 jiaxin niu,3 boris naraev,3 lida mina,3 tomislav dragovich,3 mark gimbel,3 fade mahmoud3 1department of internal medicine, division of hematology and oncology. The generic ingredient in mekinist is trametinib dimethyl sulfoxide.
Suitably, trametinib is in the form of a solvate selected from. The products dosage form is tablet, film coated, and is administered via oral form. Trametinib is approved to be used alone or with dabrafenib to treat anaplastic thyroid cancer in patients whose disease is locally advanced or has metastasized spread to other parts of the body and who cannot receive local treatment. Advise patients of the potential risk to the fetus. Suitably, trametinib is in the form of a sodium salt. The fda study data technical conformance guide states that sponsors should provide the software programs used to 1 create adam datasets, 2 generate tables and figures for primary and secondary efficacy analyses, and 3. It is also used together with dabrafenib to help prevent melanoma from coming back after surgery. Mekinist, in combination with dabrafenib, is indicated for the treatment of patients with unresectable or metastatic melanoma with braf v600e or v600k mutations, as detected by an fdaapproved test.
This drug has one hundred and eleven patent family members in fortytwo countries. Insufficient data are available in pregnant women exposed to trametinib to assess the risk. Singleagent dabrafenib but not vemurafenib has been tested against combination dabrafenibtrametinib. Melanoma, metastatic, nonsmall cell lung cancer, thyroid cancer mekinist trametinib is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with braf v600e or. Budget impact of dabrafenib and trametinib in combination. Approved for unresectable or metastatic melanoma with braf v600e or v600k mutation. All trials on the list are supported by nci ncis basic information about clinical trials explains the types and phases of trials and how they are carried out. Trametinib activity has been evaluated in the treatment of variety of cancers, and is currently approved as a monotherapy for subjects with unresectable or metastatic melanoma with braf v600ek mutation, or in. Food and drug administration 10903 new hampshire avenue silver spring, md 20993 1888info fda 18884636332 contact fda. Trametinib is an orally bioavailable mitogenactivated protein kinase mapk kinase mek inhibitor with antineoplastic activity. Enter your email address to follow this blog and receive notifications of new posts by email. May 18, 2020 the fda recently approved trametinib, a firstinclass, oral mek inhibitor for patients with unresectable or metastatic melanoma with braf v600k mutations. Trametinib is used alone or in combination with dabrafenib tafinlar to treat a certain types of melanoma a type of skin cancer that cannot be treated with surgery or that has spread to other parts of the body. To download the fda esubmitter software, click on the following link.
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