The FDA has granted approval to FoundationOne CDx as a companion diagnostic for tovorafenib (Ojemda) to identify pediatric patients with relapsed or refractory low-grade glioma (pLGG) harboring specific BRAF alterations. This approval facilitates the use of tovorafenib, a type II RAF inhibitor, in patients aged 6 months and older with BRAF fusions, rearrangements, or V600 mutations.
The approval is based on data from the phase 2 FIREFLY-1 trial (NCT04775485), which demonstrated a 67% overall response rate (ORR) (95% CI, 54%-78%) among 76 patients with BRAF-altered, relapsed or refractory pLGG treated with tovorafenib. The study also reported a 17% complete response rate and a 49% partial response rate. The clinical benefit rate (CBR) was 93%, with 26% of patients achieving stable disease as their best overall response. For patients with BRAF fusions, the ORR was 69% (95% CI, 56%-81%), while for those with BRAF V600E mutations, the ORR was 50% (95% CI, 19%-81%).
FoundationOne CDx: Detecting BRAF Alterations
FoundationOne CDx is a next-generation sequencing-based in vitro diagnostic device designed to detect substitutions, insertion and deletion alterations (indels), copy number alterations (CNAs), and select gene rearrangements in 324 genes. It also identifies genomic signatures, including microsatellite instability (MSI) and tumor mutational burden (TMB), using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. This comprehensive genomic profiling enables healthcare providers to gain a complete understanding of a patient's tumor and guide treatment decisions.
Clinical Implications and Expert Commentary
Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated, "Foundation Medicine is proud to partner with Day One to help healthcare providers connect pediatric patients and families with this treatment option. Our high-quality tissue-based companion diagnostic test is uniquely capable of detecting both BRAF V600 mutations and fusions which enables providers to gain the complete genomic picture of their patient’s tumor and guide treatment decision making."
David Arons, president and CEO of the National Brain Tumor Society, noted, "Historically, pediatric patients with pLGG have faced overwhelming side effects, both near- and long-term, from aggressive treatments like chemotherapy and radiation. We are thrilled to see that there are now additional treatment options available for these children, as well as an FDA-approved companion diagnostic test to help identify more patients who may benefit from Day One’s therapy."
Tovorafenib's Accelerated Approval
Tovorafenib received accelerated approval from the FDA in April 2024 for the treatment of patients 6 months or older with relapsed/refractory pediatric low-grade glioma harboring a BRAF fusion or rearrangement. The recommended dose of tovorafenib is 380 mg/m2 once weekly, with a maximum dose of 600 mg once weekly. The agent is administered orally on days 1, 8, 15, and 22 of 28-day cycles until disease progression or unacceptable toxicity.
Addressing Unmet Needs in pLGG
Pediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, with BRAF alterations present in up to 75% of cases. The availability of tovorafenib and its companion diagnostic, FoundationOne CDx, represents a significant advancement in the treatment landscape, offering a targeted therapy option for patients with these specific genetic alterations.
