FIREFLY-1
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.
Overview
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.
- 67 out of 100 people had their tumour shrink with Tovorafenib (arm 1).
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- 51 out of 100 people had their tumour shrink with Tovorafenib (arm 1).
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- Median 16.6 months with Tovorafenib (arm 1).
- A median is a midpoint: half the people did better than this and half did worse.
- This endpoint is not one of the standard survival or response measures; read it alongside the trial's primary result.
- These results apply to the people the trial enrolled: Relapsed or refractory BRAF-altered paediatric low-grade glioma: single-arm tovorafenib (arm 1, n = 77 registrational cohort). People in a different situation may not see the same effect.
- The trial selected people by a biomarker (BRAF); the result should not be assumed for people whose cancer does not have it.
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 participants 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 |
Pages like this
not linked directly; found by shared links- TrialTADPOLE (CDRB436G2201)
Shares RACE for Children Act, Paediatric low-grade glioma, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric, cns.
- CancerCraniopharyngioma
Shares Paediatric low-grade glioma, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric, cns.
- TrialACTION
Shares RACE for Children Act and the tags nci-coverage, paediatric, cns.
- CancerDiffuse midline glioma, H3 K27-altered (including DIPG)
Shares RACE for Children Act, Paediatric low-grade glioma and the tags nci-coverage, paediatric, cns.
- CancerEpendymoma
Shares Paediatric low-grade glioma and the tags nci-coverage, paediatric, cns.
- CancerAtypical teratoid/rhabdoid tumour (ATRT)
Shares the tags nci-coverage, paediatric, cns.
- InstitutionACCELERATE
Shares RACE for Children Act, Paediatric low-grade glioma and the tags nci-coverage, paediatric.
- InstitutionInnovative Therapies for Children with Cancer (ITCC)
Shares RACE for Children Act, Paediatric low-grade glioma and the tags nci-coverage, paediatric.