Ojemda Approved for Relapsed/Refractory BRAF-Altered Pediatric Low-Grade Glioma

The Food and Drug Administration (FDA) has granted accelerated approval to Ojemda^™ (tovorafenib) for patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.

Ojemda is an oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. The approval was based on data from the open-label, phase 2 FIREFLY-1 study (ClinicalTrials.gov Identifier: NCT04775485), which included 76 patients (median age, 8.5 years) with relapsed or refractory pediatric LGG harboring an activation BRAF alteration who had received at least 1 line of prior systemic therapy. Patients were required to have at least 1 measurable lesion as defined by RANO 2010 criteria.

Study participants received tovorafenib orally once weekly until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR), according to the Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria.

Findings showed an ORR of 51% (95% CI, 40-63), of which 37% of patients achieved partial response and 14% achieved minor response. Among responders (n=39), the median duration of response (DOR) was 13.8 months (95% CI, 11.3, not estimable). Eighty-five percent of patients had a response lasting at least 6 months and 23% had a response lasting at least 12 months. Median time to response was 5.3 months (range: 1.6, 11.2).

Among patients with BRAF fusion or rearrangement (n=64), the ORR was 52%. In patients  with BRAF V600E mutation (n=12), the ORR was 50%. Results also showed an ORR of 49% among patients who had prior MAPK-targeted therapy (n=45), and 55% among patients who did not receive prior MAPK-targeted therapy (n=31).

“The goal of pLGG treatment is to stabilize or shrink the tumor without further disrupting the child’s and family’s life,” said FIREFLY-1 study investigator Dr Sabine Mueller, pediatric neuro-oncologist, University of California San Francisco Benioff Children’s Hospitals. “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 reactions reported with tovorafenib were 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 4 laboratory abnormalities were decreased phosphate, decreased hemoglobin, increased creatinine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate aminotransferase, decreased potassium, and decreased sodium.

Ojemda is supplied as a tablet (100mg) or an oral suspension (25mg/mL). Prior to initiating treatment, the presence of BRAF fusion or rearrangement, or BRAF V600 mutation should be confirmed. The recommended dosage of Ojemda is based on body surface area and is administered once weekly.