FDA grants Ojemda accelerated approval for children with advanced low-grade brain cancer
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The FDA granted accelerated approval to Ojemda for the treatment of certain children with relapsed or refractory low-grade glioma.
The indication applies to children aged 6 months or older whose tumors harbor a BRAF fusion or rearrangement or BRAF V600 mutation.
Tovorafenib (Ojemda, Day One Biopharmaceuticals) is an investigational kinase inhibitor that targets a key enzyme in the MAPK signaling pathway. The agent previously received breakthrough and orphan drug designations from the FDA.
The agency gave accelerated approval based on results from the open-label FIREFLY-1 trial, which assessed the efficacy of tovorafenib in 76 children with relapsed or refractory pediatric low-grade glioma (pLGG) harboring an activating BRAF alteration.
Study participants received at least one prior line of systemic therapy, had documented evidence of radiographic progression and at least one measurable lesion. The study excluded patients with tumors harboring additional activating molecular alternations or with a known or suspected diagnosis of neurofibromatosis type 1.
Overall response rate served as the major efficacy outcome measurement, defined as the proportion of patients with complete, partial or minor responses. The pivotal trial also assessed duration of response.
Results showed an ORR of 51% (95% CI, 40-63) and a median duration of response of 13.8 months (95% CI, 11.3 to not estimable); study investigators also noted a median time to treatment response of 5.3 months (range, 1.6-11.2).
“pLGG is a chronic and relentless cancer that can devastate children and their families, often stealing their vision, balance and speech,” Sabine Mueller, MD, PhD, MAS, pediatric neuro-oncologist at University of California San Francisco Benioff Children’s Hospitals, said in a Day One-issued press release. “The goal of pLGG treatment is to stabilize or shrink the tumor without further disrupting the child’s and family’s life. Historically, there has been no standard of care for children with pLGG] who have relapsed. We are excited to welcome a new targeted treatment option with once-weekly oral dosing designed specifically for these kids and their families.”
The most common adverse events affecting at least 30% of the patients in the FIREFLY-1 study included rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform and upper respiratory tract infection.
The most common grade 3 or grade 4 laboratory abnormalities affecting more than 2% of the patient population included decreased phosphate, decreased hemoglobin, increased creatinine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate aminotransferase, decreased potassium and decreased sodium.
The recommended dose of tovorafenib based on body surface area is 380 mg/m2 orally once a week, with a maximum dose of 600 mg orally once a week, with or without food until either disease progression or unacceptable toxicity.
The FDA said it granted accelerated approval based on ORR and duration of response data and that a confirmatory trial to confirm the clinical benefits of the therapy may be required to maintain the indication’s approval.
References:
- FDA grants accelerated approval to tovorafenib for patients with relapsed or refractory BRAF-altered pediatric low-grade glioma (press release). Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tovorafenib-patients-relapsed-or-refractory-braf-altered-pediatric. Published April 23, 2024. Accessed April 23, 2024.
- Day One’s Ojemda (tovorafenib) receives US FDA accelerated approval for relapsed or refractory BRAF-altered pediatric low-grade glioma (pLGG), the most common form of childhood brain tumor (press release). Available at: https://ir.dayonebio.com/news-releases/news-release-details/day-ones-ojemdatm-tovorafenib-receives-us-fda-accelerated. Published April 23, 2024. Accessed April 23, 2024.
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