FDA approves dabrafenib with trametinib for pediatric patients with low-grade glioma with a BRAF V600E mutation
Regulatory approval: On March 16, 2023, the FDA approved dabrafenib plus trametinib for pediatric patients aged ≥1 year with low-grade glioma (WHO grade 1–2) harboring a BRAF V600E mutation who require systemic therapy. The agency also approved new oral formulations for patients unable to swallow pills. Approval was supported by Study CDRB436G2201, where dabrafenib/trametinib improved ORR and PFS versus carboplatin/vincristine; interim OS was not statistically significant.
FDA approval (March 16, 2023)
The FDA approved dabrafenib (Tafinlar) with trametinib (Mekinist) for pediatric patients ≥1 year with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy. The FDA also approved new oral formulations of both drugs for patients who cannot swallow pills. The FDA stated this is the first approval of a systemic therapy for first-line treatment of pediatric LGG with a BRAF V600E mutation.
Key efficacy evidence
Approval was based on Study CDRB436G2201 (NCT02684058), a multicenter, open-label trial in LGG (WHO grades 1–2) requiring first systemic therapy, randomized 2:1 to dabrafenib+trametinib (D+T) vs carboplatin+vincristine (C+V). Primary endpoint was ORR by independent review using RANO LGG (2017).
In the LGG cohort (D+T n=73; C+V n=37):
- ORR: 46.6% (95% CI 34.8–58.6) vs 10.8% (95% CI 3.0–25.4); p<0.001
- PFS: 20.1 vs 7.4 months; HR 0.31 (95% CI 0.17–0.55); p<0.001
- Interim OS (≥32 weeks follow-up) was not statistically significant; 1 death occurred in the C+V arm.
Safety (pooled pediatric D+T, N=166)
Common adverse reactions (>20%) included pyrexia (66%), rash (54%), headache (40%), vomiting (38%), and diarrhea (30%). Grade 3/4 lab abnormalities included decreased neutrophils (20%).
The review was conducted under Project Orbis; reviews at other agencies were ongoing at the time of the FDA communication.