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FIREFLY-1 showed that a once-weekly pill, tovorafenib, shrinks most relapsed childhood low-grade gliomas driven by BRAF changes, including the common KIAA1549-BRAF fusion that older BRAF drugs could not treat safely. It led to the first approval of a drug for this disease.
Open-label phase 2 of tovorafenib, an oral type II RAF inhibitor that does not cause the paradoxical MAPK activation seen with type I BRAF inhibitors in BRAF-fusion tumours. In the registrational arm 1 (n = 77), independent review found an overall response rate of 67% by RANO-HGG criteria (the prespecified primary endpoint) and 51% by RAPNO-LGG criteria including minor responses; median duration of response 16.6 months and median time to response 3.0 months. Treatment-related adverse events led to discontinuation in 7% of patients; hair colour change, elevated creatine phosphokinase, anaemia and slowed growth velocity were characteristic. FDA accelerated approval followed on 23 April 2024 for relapsed or refractory paediatric LGG with BRAF fusion or rearrangement or BRAF V600 mutation. The confirmatory phase 3 LOGGIC/FIREFLY-2 trial compares tovorafenib with chemotherapy in the front line.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
141 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall response rate (RANO-HGG, independent review)primary | Tovorafenib (arm 1) | 77 | 67% | - | - | link |
| Overall response rate (RAPNO-LGG, including minor responses) | Tovorafenib (arm 1) | 77 | 51% | - | - | link |
| Median duration of response | Tovorafenib (arm 1) | - | 16.6 months | - | - | link |
Shares RACE for Children Act, Paediatric low-grade glioma, Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first, BRAF and the tags paediatric, cns.
Shares RACE for Children Act, Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first and the tags paediatric, cns.
Shares Paediatric low-grade glioma, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags paediatric, cns.
Shares RACE for Children Act, Paediatric low-grade glioma, Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first and the tags paediatric, cns.
Shares Paediatric low-grade glioma and the tags paediatric, cns.
Shares the tags paediatric, cns.
Shares the tags paediatric, cns.
Shares Paediatric low-grade glioma, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags paediatric, cns.