Ojemda (tovorafenib)
Research Synopsis
- - Tovorafenib, marketed as Ojemda, is a selective oral medication approved for treating pediatric low-grade glioma (pLGG) and advanced solid tumors with specific genetic mutations in the MAPK pathway.
- - The drug acts as a type II RAF kinase inhibitor, effectively targeting BRAF alterations, including mutant V600E and wild-type BRAF and CRAF, thereby addressing abnormal signaling associated with these mutations.
- - Research highlighted in a 2023 phase 1 study demonstrated that tovorafenib exhibited promising safety and efficacy profiles, particularly in melanoma patients harboring BRAF and NRAS mutations.
- - Phase 2 trials, such as FIREFLY-1, indicated an overall response rate of 67% in patients with BRAF-altered, relapsed/refractory pLGG, with manageable side effects that included hair color changes and elevated creatine phosphokinase.
- - The FDA approved tovorafenib in April 2024 for patients aged 6 months and older with specific forms of relapsed or refractory pediatric low-grade gliomas, based on successful trial outcomes.
- - Comparative studies suggest that tovorafenib performs well against low-grade gliomas harboring BRAF fusions, expanding targeted treatment options away from conventional therapies.
- - Current research efforts are directed toward understanding tovorafenib's role in treating pediatric low-grade gliomas, with ongoing randomized trials such as LOGGIC/FIREFLY-2 aimed at comparing its effectiveness against standard chemotherapy.
- - Significant advancements in targeted therapy are noted, with tovorafenib being a promising alternative to older first-generation BRAF inhibitors by showing improved activity and reduced risk of paradoxical activation.
- - The continuing emergence of phase 3 trials and critical reviews underscores the importance of developing targeted treatments like tovorafenib to manage the increasing incidence of BRAF-mutated gliomas effectively.
- - Overall, recent findings position tovorafenib as a vital player in the evolving landscape of cancer therapy, particularly for pediatric patients, highlighting its role in addressing unmet medical needs in this population.
Ojemda (tovorafenib)
Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib.
London, UK
2 hours ago
1 Received
- - Upon activation by RAS, RAF kinases trigger the MAP kinase cascade to regulate cell growth, with BRAF mutations being particularly common in cancers like malignant melanoma.
- - Current selective BRAF inhibitors are ineffective against cancers fueled by oncogenic RAS or certain BRAF mutations, leading to the development of "type II" RAF inhibitors that target RAF dimers instead.
- - Studies on type II inhibitors tovorafenib and naporafenib show they are most effective against CRAF while being less so against ARAF, revealing their unique binding modes and highlighting potential clinical implications for cancer treatment.
$100 - $150
Hourly Rate
Activity of Type II RAF Inhibitor Tovorafenib in a Pediatric Patient With a Recurrent Spindle Cell Sarcoma Harboring a Novel Gene Fusion.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Phase 1 study of the pan-RAF inhibitor tovorafenib in patients with advanced solid tumors followed by dose expansion in patients with metastatic melanoma.
London, UK
2 hours ago
1 Received
- Tovorafenib, a new oral treatment targeting tumors with BRAF and NRAS mutations, was evaluated in a phase 1 clinical study for safety and effectiveness in advanced solid tumors, particularly melanoma.
- The study involved 149 patients and established the recommended phase 2 dose (RP2D) as 200 mg every other day or 600 mg weekly, with common side effects including anemia and rash.
- Some patients with BRAF mutation-positive melanoma showed a partial response, while those with NRAS mutations had stable disease, prompting a preference for the weekly dosing schedule for future research.
$100 - $150
Hourly Rate
Targeted Options for Glioma Looking Good.
London, UK
2 hours ago
1 Received
- The phase III INDIGO trial showed that vorasidenib, an IDH1/2 inhibitor, effectively helps adults with IDH1/2-mutant low-grade gliomas by lowering the risk of disease progression and postponing the need for chemoradiotherapy.
- In a separate pediatric study called FIREFLY-1, a phase II trial, tovorafenib (a type II pan-RAF inhibitor) demonstrated strong responses in children with low-grade gliomas.
- These findings suggest promising treatment options for both adult and pediatric patients dealing with low-grade gliomas, indicating advances in targeted therapies.
$100 - $150
Hourly Rate
LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration.
London, UK
2 hours ago
1 Received
- Pediatric low-grade glioma (pLGG) is mainly caused by genomic changes in the MAPK pathway, particularly KIAA1549::BRAF fusions and BRAF V600E mutations, making it suitable for targeted therapies like tovorafenib instead of traditional treatments.
- The combination of dabrafenib and trametinib is FDA-approved for BRAF V600E-pLGG but not effective for tumors with BRAF fusions, as it may worsen tumor growth.
- The LOGGIC/FIREFLY-2 trial is assessing tovorafenib against standard chemotherapy in patients under 25 with pLGG and BRAF mutations, focusing on overall response rate and safety.
$100 - $150
Hourly Rate
The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial.
London, UK
2 hours ago
1 Received
- The trial demonstrated an overall response rate of 67% and a median duration of response of 16.6 months based on RANO-HGG criteria, while the RAPNO criteria showed an overall response rate of 51% and median duration of response of 13.8 months.
- Common treatment-related side effects included hair color changes (76%), elevated creatine phosphokinase
$100 - $150
Hourly Rate
Tovorafenib effective against low-grade gliomas harbouring BRAF fusions.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
How will tovorafenib change our treatment of pediatric low-grade glioma?
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Author Correction: The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Tovorafenib (Ojemda) for pediatric low-grade glioma.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Tovorafenib: First Approval.
London, UK
2 hours ago
1 Received
- * The drug acts as a type II RAF kinase inhibitor, working against mutant BRAF V600E as well as wild-type BRAF and CRAF, targeting abnormal signaling in affected cells.
- * In April 2024, tovorafenib received FDA approval for use in patients aged 6 months and older with certain forms of relapsed or refractory pediatric low-grade gliomas based on positive results from the pivotal phase 2 FIREFLY-1 study.
$100 - $150
Hourly Rate
A critical review of RAF inhibitors in BRAF-mutated glioma treatment.
London, UK
2 hours ago
1 Received
- * The review highlights first-generation BRAF inhibitors like Vemurafenib, Dabrafenib, and Encorafenib, and discusses the complications of paradoxical ERK activation that can occur with these treatments.
- * New pan-RAF inhibitors, particularly Tovorafenib, showcase improved effectiveness and the ability to cross the blood-brain barrier while avoiding paradoxical activation, highlighting the need for ongoing research in this area.
$100 - $150
Hourly Rate
Type II RAF inhibitor tovorafenib for the treatment of pediatric low-grade glioma.
London, UK
2 hours ago
1 Received
- Pediatric low-grade glioma (pLGG) is the most common type of brain tumor in children and is now treated as a chronic disease; recently, the FDA approved a new drug, tovorafenib, for patients aged 6 months and older with specific genetic mutations in pLGG.
- The article reviews tovorafenib's pharmacological properties, effectiveness, and safety through a systematic search of relevant publications.
- Tovorafenib is the first FDA-approved treatment for pediatric patients with common BRAF mutations in pLGG, exhibiting good CNS penetration and demonstrating positive clinical results in trials with minimal side effects.
$100 - $150
Hourly Rate