Trametinib
- Generic Name
- Trametinib
- Brand Names
- Mekinist, Spexotras
- Drug Type
- Small Molecule
- Chemical Formula
- C26H23FIN5O4
- CAS Number
- 871700-17-3
- Unique Ingredient Identifier
- 33E86K87QN
- Background
Trametinib is an orally bioavailable mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 inhibitor. It was first approved by the FDA in May 2013 for the treatment of melanoma. It was later approved by Health Canada on July 18, 2013 and by the European Commission on June 30, 2014. Trametinib is currently approved to treat a variety of cancers with BRAF mutations, such as non-small cell lung cancer and thyroid cancer, as monotherapy or in combination with dabrafenib, a BRAF inhibitor, for improved therapeutic efficacy. Originally developed by Japan Tobacco, trametinib was initially investigated for treating inflammation, but further studies for this indication were not pursued.
- Indication
Trametinib is indicated as monotherapy for the treatment of BRAF-inhibitor treatment-naïve patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations.
It is used in combination with dabrafenib for the:
In the US, BRAF V600E or V600K mutations must be detected by an FDA-approved test. Trametinib is not indicated for the treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition.
- Associated Conditions
- Advanced Non-Small Cell Lung Cancer (NSCLC), Locally Advanced Anaplastic Thyroid Cancer, Low-Grade Glioma, Melanoma, Metastatic Anaplastic Thyroid Cancer, Metastatic Melanoma, Metastatic Non-Small Cell Lung Cancer, Stage III Melanoma, Unresectable Melanoma, Unresectable or Metastatic Solid Tumors
GSK and Novartis Complete $16 Billion Asset Swap Deal, Reshaping Both Companies' Strategic Focus
• GlaxoSmithKline and Novartis have completed their $16 billion asset swap deal, with GSK exchanging its oncology portfolio for Novartis's vaccines business, while also creating a joint consumer healthcare venture.
• Analysts question GSK's decision to exit oncology—a high-growth therapeutic area where its portfolio showed 32% growth in 2014—while Novartis is praised for strengthening its position in the lucrative cancer market.
• The strategic realignment allows both companies to focus on core strengths, with GSK concentrating on respiratory, HIV, vaccines and consumer healthcare, while Novartis enhances its prescription medicine portfolio with particular emphasis on oncology.
Pharmac to Fund Advanced Melanoma Treatments in New Zealand Starting June 2025
• Pharmac has announced funding for pembrolizumab (Keytruda) and BRAF inhibitors dabrafenib (Tafinlar) and trametinib (Mekinist) for stage 3B and more advanced melanoma patients in New Zealand, effective June 1, 2025.
• The expanded access brings New Zealand closer to international standards of care, allowing oncologists to offer immunotherapy before and/or after surgery to reduce tumor size and prevent recurrence.
• The decision represents a significant advancement for melanoma treatment in New Zealand, where patients previously had limited funded options compared to other countries including neighboring Australia.
Hikma Acquires FDA-Approved Generic Trametinib ANDA, Securing 180-Day Market Exclusivity
• Hikma Pharmaceuticals has acquired Novugen's FDA-approved ANDA for trametinib tablets, the generic version of Mekinist®, with 180 days of US market exclusivity upon launch.
• The commercial agreement positions Hikma to handle US sales and marketing while Novugen will manufacture the oncology treatment, which had approximately $436 million in US sales in 2024.
• This strategic acquisition strengthens Hikma's pipeline in growing therapeutic areas, particularly in oncology, expanding access to cost-efficient cancer treatments for US patients.
Meta-Analysis Confirms Tafinlar-Mekinist Combination's Efficacy Across Age Groups in Glioma Treatment
• A comprehensive meta-analysis of 243 patients demonstrates that the Tafinlar-Mekinist combination achieves significant response rates in both pediatric (53%) and adult (39%) glioma patients.
• The drug combination shows comparable safety profiles between age groups, with pooled side effect rates of 96% in pediatric and 83% in adult patients, though the difference was not statistically significant.
• The FDA's March 2023 approval of Tafinlar-Mekinist for BRAF V600E low-grade gliomas marks the first systemic therapy approval for pediatric brain cancer patients aged one and older.
Experts Address Key Challenges in Implementation of Tumor-Agnostic Therapies and Genetic Testing
• The increasing adoption of tumor-agnostic therapies has highlighted the need for universal genetic testing in oncology practices, with eight drugs now holding FDA pan-tumor approvals as of January 2025.
• Healthcare providers face complex decisions regarding genetic testing methodologies, including choices between tissue and liquid biopsies, timing of collection, and interpretation of results.
• Clinical implementation challenges include establishing efficient testing workflows, securing genetic counseling resources, and determining appropriate treatment sequencing in cases with limited tumor-specific data.
Arvinas Advances Vepdegestrant into Phase 3 Trials for Breast Cancer and Updates Pipeline Milestones
• Arvinas plans to initiate two Phase 3 trials in 2025 for vepdegestrant in ER+/HER2- metastatic breast cancer, one in the first-line setting with atirmociclib and another in the second-line setting with a CDK4/6 inhibitor.
• Topline data from the Phase 3 VERITAC-2 monotherapy trial of vepdegestrant in second-line-plus ER+/HER2- metastatic breast cancer is anticipated in the first quarter of 2025.
• Arvinas is set to present initial data from the Phase 1 trial of ARV-393 in B-cell lymphomas and file an IND application for a novel PROTAC KRAS G12D degrader in 2025.
• Phase 1 trial with PROTAC LRRK2 degrader ARV-102 in patients with Parkinson’s disease has been initiated, with data expected to be presented in the first half of 2025.
Biopharma Industry Faces Continued Layoffs in 2025 Amid Strategic Realignments
• Biopharma companies continue to announce layoffs in 2025, driven by strategic realignments, pipeline reprioritizations, and challenging financial conditions.
• Several companies, including Intellia Therapeutics and IGM Biosciences, are cutting a significant portion of their workforce to focus on key programs and extend cash runways.
• These workforce reductions are often accompanied by discontinuation of certain drug development programs and a shift in strategic focus towards core assets.
• The layoffs reflect a broader trend in the industry as companies adapt to evolving market dynamics and prioritize efficiency and long-term sustainability.
Penn Medicine's Lynn Schuchter: Three Decades of Pioneering Melanoma Treatment and Research
• Dr. Lynn Schuchter has dedicated 30 years at Penn Medicine to advancing melanoma treatment, leading groundbreaking research in targeted therapies and immunotherapy approaches.
• As director of the Tara Miller Melanoma Center and former division chief of hematology/oncology, Dr. Schuchter helped expand the faculty from 35 to 150 positions while maintaining focus on patient-centered care.
• Under her leadership, significant breakthroughs were achieved in melanoma treatment, including the development of BRAF-targeted therapies and combination treatments that have dramatically improved patient outcomes.
Pfizer's Braftovi Combo Shows Survival Benefit in BRAF-Mutated Metastatic Colorectal Cancer
• Pfizer's Braftovi, combined with cetuximab and mFOLFOX6, significantly improved progression-free survival in metastatic colorectal cancer patients with BRAF V600E mutation.
• The BREAKWATER trial demonstrated a clinically meaningful improvement in overall survival with the Braftovi regimen compared to chemotherapy.
• The FDA granted accelerated approval to the Braftovi combination in December 2024, marking it as a first-line targeted therapy option.
• Pfizer plans to share the BREAKWATER data with regulatory authorities to support full approval and broader use of the Braftovi combination.
Tafinlar and Mekinist Show Long-Term Mortality Reduction in Stage III Melanoma
• Final analysis of the COMBI-AD trial reveals that Tafinlar plus Mekinist provides sustained relapse-free and distant metastasis-free survival benefits in resected stage III melanoma patients.
• The combination therapy demonstrated a 20% reduction in the risk of death overall, with a more pronounced 25% reduction observed in patients harboring the BRAF V600E mutation.
• After over eight years of follow-up, the safety profile of Tafinlar and Mekinist remained consistent with previous findings, showing no new long-term safety concerns.
• While the overall survival benefit was not statistically significant, the findings support the use of Tafinlar and Mekinist as adjuvant therapy in high-risk melanoma.
FDA Approves Caris Life Sciences' MI Cancer Seek as Companion Diagnostic
• The FDA has approved MI Cancer Seek, a comprehensive companion diagnostic test by Caris Life Sciences, for both adult and pediatric cancer patients.
• MI Cancer Seek utilizes simultaneous whole exome and whole transcriptome sequencing to identify patients who may benefit from targeted therapies.
• This approval includes one pan-cancer and five tumor-specific indications, covering numerous FDA-approved therapies, enhancing precision medicine.
• The test aims to provide a comprehensive molecular blueprint, saving tissue and time by combining DNA and RNA analysis in a single process.
FDA Approves Caris Life Sciences' MI Cancer Seek as Companion Diagnostic
• Caris Life Sciences' MI Cancer Seek receives FDA approval as a companion diagnostic for targeted cancer therapies, benefiting both adult and pediatric patients.
• MI Cancer Seek is the first assay to simultaneously use Whole Exome Sequencing (WES) and Whole Transcriptome Sequencing (WTS) with FDA-approved companion diagnostic indications.
• The diagnostic tool identifies single nucleotide variants, microsatellite instability, and tumor mutational burden in solid tumors to guide treatment decisions.
• The FDA's approval underscores Caris' commitment to advancing precision medicine and providing clinicians with advanced tools for personalized cancer treatment strategies.
FDA Approves MI Cancer Seek as Companion Diagnostic for Targeted Therapy Across Tumor Types
• The FDA has approved MI Cancer Seek as a companion diagnostic to identify cancer patients who may benefit from targeted therapy, covering both adult and pediatric populations.
• MI Cancer Seek is the first FDA-approved assay that combines whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) for molecular profiling of solid tumors.
• The diagnostic can detect single nucleotide variants, insertions, deletions, microsatellite instability (MSI), and tumor mutational burden (TMB) across multiple cancer types.
• MI Cancer Seek holds companion diagnostic indications in breast, colorectal, melanoma, non-small cell lung, and endometrial cancers, guiding treatment decisions with targeted therapies.
FDA Approves Caris Life Sciences' MI Cancer Seek as Companion Diagnostic
• The FDA has approved Caris Life Sciences' MI Cancer Seek as a companion diagnostic to identify cancer patients who may benefit from targeted therapies.
• MI Cancer Seek is the first assay to use simultaneous Whole Exome Sequencing (WES) and Whole Transcriptome Sequencing (WTS) with CDx indications.
• The diagnostic test is available for both adult and pediatric patients (ages 1-22) with previously diagnosed solid tumors.
• MI Cancer Seek can detect SNVs, indels, MSI, TMB, and CNAs, providing a comprehensive molecular profile for precision medicine.
Caris Life Sciences' MI Cancer Seek Receives FDA Approval as Companion Diagnostic
• Caris Life Sciences' MI Cancer Seek receives FDA approval as a companion diagnostic for targeted cancer therapies, benefiting both adult and pediatric patients.
• MI Cancer Seek is the first assay to simultaneously use Whole Exome Sequencing (WES) and Whole Transcriptome Sequencing (WTS) with FDA-approved CDx indications.
• The diagnostic tool identifies single nucleotide variants, insertions, deletions, microsatellite instability, and tumor mutational burden in solid tumors.
• MI Cancer Seek supports treatment decisions across multiple cancers, including breast, colorectal, melanoma, non-small cell lung cancer, and endometrial carcinoma.
Erasca's Naporafenib Shows Promise in NRAS-Mutant Melanoma, RAS Targeting Franchise Advances
• Erasca's Naporafenib, combined with trametinib, demonstrates potential for durable efficacy in NRAS-mutant melanoma, addressing a critical unmet need after frontline immunotherapy.
• Phase 1b SEACRAFT-1 trial data supports a tissue-specific approach, reducing dermatologic toxicities through mandatory primary prophylaxis, reinforcing the ongoing Phase 3 SEACRAFT-2 trial.
• Erasca's RAS targeting franchise, including ERAS-0015 and ERAS-4001, progresses rapidly with planned IND submissions on track for early 2025, expanding treatment options for RAS/MAPK pathway-driven cancers.
FDA Approves Novartis' Tafinlar + Mekinist Combo for BRAF V600E-Mutated Solid Tumors
• The FDA granted accelerated approval to Novartis' Tafinlar and Mekinist combination for advanced solid tumors harboring the BRAF V600E mutation after prior therapy and no alternative options.
• This marks the first BRAF/MEK inhibitor approved for pediatric patients, expanding its use to individuals as young as six years old.
• The approval was based on clinical trials demonstrating efficacy and safety, with overall response rates reaching up to 80% in some tumor types.
• The expanded approval potentially covers over 20 different tumor types, including gliomas, biliary tract cancer, and gynecological and gastrointestinal cancers.
FDA Grants Accelerated Approval to Dabrafenib and Trametinib Combination for BRAF V600E-Mutated Solid Tumors
• The FDA granted accelerated approval to Novartis' dabrafenib and trametinib combination for BRAF V600E-mutated solid tumors.
• This approval targets adult and pediatric patients (≥6 years) with unresectable or metastatic tumors who progressed after prior treatment.
• The therapy is indicated for patients lacking satisfactory alternative treatment options, addressing an unmet need in advanced solid tumors.
• Novartis' Tafinlar and Mekinist demonstrated efficacy in a study, supporting the FDA's decision for accelerated approval.
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