CLINICAL TRIALS PROFILE FOR TRAMETINIB DIMETHYL SULFOXIDE

All Clinical Trials for trametinib dimethyl sulfoxide

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01902173 ↗	Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer	Active, not recruiting	GlaxoSmithKline	Phase 1/Phase 2	2013-07-19	This phase I/II trial studies the side effects and the best dose of uprosertib when given together with dabrafenib and trametinib and to see how well they work in treating patients with stage IIIC-IV cancer. Uprosertib, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving uprosertib with dabrafenib and trametinib may be a better treatment for cancer.
NCT01902173 ↗	Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer	Active, not recruiting	Novartis Pharmaceuticals	Phase 1/Phase 2	2013-07-19	This phase I/II trial studies the side effects and the best dose of uprosertib when given together with dabrafenib and trametinib and to see how well they work in treating patients with stage IIIC-IV cancer. Uprosertib, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving uprosertib with dabrafenib and trametinib may be a better treatment for cancer.
NCT01902173 ↗	Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer	Active, not recruiting	National Cancer Institute (NCI)	Phase 1/Phase 2	2013-07-19	This phase I/II trial studies the side effects and the best dose of uprosertib when given together with dabrafenib and trametinib and to see how well they work in treating patients with stage IIIC-IV cancer. Uprosertib, dabrafenib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving uprosertib with dabrafenib and trametinib may be a better treatment for cancer.
NCT01725100 ↗	A Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies	Completed	GlaxoSmithKline	Phase 1	2013-02-05	This is an open-label, randomized, single-dose, 2-treatment, 2-period, 2-way crossover study with incomplete wash-out in subjects with solid tumors to determine the relative bioavailability of test formulation with lower dimethyl sulfoxide (DMSO) content as compared with standard reference formulation trametinib. Approximately 18 subjects will be randomized to receive either a single dose of Treatment A (standard target DMSO content [theoretical 11.3%] formulation of GSK1120212B) or a single dose of Treatment B (lower DMSO Content [approximately 9.5%] formulation of GSK1120212B) followed by a 7 day incomplete wash-out period, then a single dose of the other treatment. Administration of the dose under fasted conditions in Periods 1 and 2 will be only on Day 1 followed by 7 days of serial blood sampling for PK analysis of plasma trametinib. Safety assessments, including assessment of AEs, clinical laboratory (hematology and clinical chemistry) and vital signs, will be made throughout the study. After a subject completes the study, he or she may be eligible to enter study MEK114375, an open-label rollover study of trametinib (no wash-out period or follow-up visit required) and continue receiving trametinib. For those subjects who wish to discontinue or complete the current study and choose not enter the rollover study, a follow-up visit should be performed within 21 days after receiving the last dose of study treatment.

Clinical Trial Conditions for trametinib dimethyl sulfoxide

Condition Name

Condition Name for trametinib dimethyl sulfoxide
Intervention	Trials
Hematopoietic and Lymphoid Cell Neoplasm	5
Refractory Malignant Solid Neoplasm	4
Refractory Plasma Cell Myeloma	4
Advanced Lymphoma	4

Condition MeSH

Condition MeSH for trametinib dimethyl sulfoxide
Intervention	Trials
Neoplasms	7
Skin Neoplasms	5
Melanoma	5
Neoplasms, Plasma Cell	4

Clinical Trial Locations for trametinib dimethyl sulfoxide

Trials by Country

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−

Trials by Country for trametinib dimethyl sulfoxide
Location	Trials
United States	209
United Kingdom	4
Puerto Rico	1

Trials by US State

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−

Trials by US State for trametinib dimethyl sulfoxide
Location	Trials
Pennsylvania	11
Maryland	6
Georgia	6
Texas	6
Ohio	6

Clinical Trial Progress for trametinib dimethyl sulfoxide

Clinical Trial Phase

Clinical Trial Phase for trametinib dimethyl sulfoxide
Clinical Trial Phase	Trials
Phase 3	1
Phase 2/Phase 3	1
Phase 2	9

Clinical Trial Status

Clinical Trial Status for trametinib dimethyl sulfoxide
Clinical Trial Phase	Trials
Active, not recruiting	9
Completed	2
Recruiting	2

Clinical Trial Sponsors for trametinib dimethyl sulfoxide

Sponsor Name

Sponsor Name for trametinib dimethyl sulfoxide
Sponsor	Trials
National Cancer Institute (NCI)	12
GlaxoSmithKline	2
NRG Oncology	1

Sponsor Type

Sponsor Type for trametinib dimethyl sulfoxide
Sponsor	Trials
NIH	13
Other	3
Industry	3

Trametinib Dimethyl Sulfoxide: Clinical Trials, Market Analysis, and Projections

Introduction

Trametinib dimethyl sulfoxide, known by its brand name Mekinist, is a significant player in the treatment of various cancers, particularly those with BRAF mutations. This article will delve into the current clinical trials, market analysis, and future projections for this drug.

Clinical Trials Overview

Current Trials and Objectives

Trametinib is currently involved in several clinical trials across different cancer types. One notable trial is the phase I/II study combining trametinib with dabrafenib and uprosertib for patients with stage IIIC-IV cancer, particularly those with BRAF mutant cancer. The primary objectives include assessing the safety and optimal dose of the combination therapy and evaluating the objective response rate[1].

In another context, trametinib is being investigated for its efficacy in treating high-grade glioma. This phase II trial by Novartis aims to determine the safety and efficacy of trametinib in this indication, although historical data for phase II drugs in this area is limited[4].

Combination Therapies

Trametinib is often used in combination with other therapies to enhance its efficacy. For instance, the combination of trametinib with dabrafenib has been approved for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. This combination has demonstrated durable response rates, although it has not shown improvement in overall survival or disease-related symptoms compared to monotherapy[2][5].

Recent trials, such as the COMBI-i clinical trial, have shown promising results with the triple combination of Tafinlar (dabrafenib), Mekinist (trametinib), and spartalizumab, an investigational anti-PD-1 immunotherapy. This combination significantly improved progression-free survival and overall survival rates compared to the combination of Tafinlar and Mekinist alone[3].

Mechanism of Action

Trametinib is a reversible, highly selective, allosteric inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2. These proteins are critical in the central signal transduction pathway and are essential for cell proliferation and survival. By inhibiting MEK1 and MEK2, trametinib targets known oncogenic mutations in the MAPK pathway, particularly those involving BRAF and Ras[2][5].

Market Analysis

Current Market Size and Growth

The melanoma market, where trametinib is a key player, has seen significant growth. As of 2023, the melanoma market size was valued at USD 3.9 billion and is projected to reach USD 8.9 billion by 2034, exhibiting substantial growth driven by advancements in screening techniques and therapeutic options[3].

Competitive Landscape

Trametinib competes in a market dominated by targeted therapies and immunotherapies. The approval of combination therapies involving trametinib and other agents like dabrafenib and immunotherapies has strengthened its position. However, the market remains competitive with other drugs and combinations being developed and approved for similar indications[3].

Projections and Future Outlook

Expanding Indications

Trametinib is under development for a wide range of cancers beyond melanoma, including high-grade glioma, cholangiocarcinoma, metastatic biliary tract carcinoma, differentiated thyroid cancer, and several others. This broadening of indications is expected to further increase its market presence and patient reach[4].

Combination Therapies and Immunotherapy

The future of trametinib lies in its use in combination with other therapies, particularly immunotherapies. Trials like the IMspire150 and COMBI-i have shown the potential of such combinations in improving patient outcomes. As more data becomes available, these combinations are likely to become standard treatments for various cancers[3].

Regulatory and Approval Landscape

Trametinib has already received approvals for its use in combination with dabrafenib for melanoma and other BRAF V600 mutation-positive cancers. Ongoing trials and positive results are expected to lead to additional approvals, further solidifying its position in the oncology market[2][5].

Key Takeaways

• Clinical Trials: Trametinib is involved in multiple clinical trials, including phase I/II studies for BRAF mutant cancers and phase II trials for high-grade glioma.
• Mechanism of Action: Trametinib inhibits MEK1 and MEK2, targeting oncogenic mutations in the MAPK pathway.
• Market Analysis: The melanoma market is growing, with trametinib being a significant player, especially in combination therapies.
• Projections: Trametinib is expected to expand its indications and continue to be used in combination with other therapies, including immunotherapies.

FAQs

What is the primary mechanism of action of trametinib?

Trametinib is a reversible, highly selective, allosteric inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2, critical for cell proliferation and survival[2][5].

Which cancers is trametinib currently approved for?

Trametinib is approved for the treatment of adult patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, often in combination with dabrafenib[2][5].

What are the ongoing clinical trials for trametinib?

Trametinib is currently in phase I/II trials for BRAF mutant cancers and in phase II trials for high-grade glioma, among other indications[1][4].

How does the combination of trametinib with dabrafenib and immunotherapies impact patient outcomes?

The combination of trametinib with dabrafenib and immunotherapies has shown significant improvements in progression-free survival and overall survival rates compared to monotherapy or dual therapy alone[3].

What is the projected market size for the melanoma market by 2034?

The melanoma market is projected to reach USD 8.9 billion by 2034, driven by advancements in screening techniques and therapeutic options[3].

Sources

1. ClinicalTrials.gov: Uprosertib, Dabrafenib, and Trametinib in Treating Patients With Stage IIIC-IV Cancer.
2. EMA: CHMP assessment report - Mekinist.
3. BioSpace: Melanoma Market to Reach USD 8.9 Billion by 2034.
4. Pharmaceutical Technology: Trametinib dimethyl sulfoxide by Novartis for High-Grade Glioma.
5. TGA: Australian public assessment report for trametinib (as dimethyl sulfoxide).