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Day One Biopharmaceuticals Announces Top Line Data for the FIREFLY-1 Pivotal Phase 2 Trial in Pediatric Low Grade Glioma
Meaningful clinical responses to tovorafenib suggest an important new tool in the Brain Cancer Toolbox
We spend a fair bit of time on this forum talking about GBM and other High Grade Gliomas (HGGs), but there are other brain cancers that fall into the categories of Low Grade Gliomas (LGGs). At MissionGBM, we are frequently contacted by patients and their families who have been diagnosed with Grade 1-2 LGGs, and are looking for information and resources. Some of the patients are children.
For pediatric LGG patients, the press release from Day One Biopharmaceuticals announcing significant clinical trials results from the pivotal Phase 2 FIRELFY-1 trial of tovorafenib represents good news.
Summary of Top Line Clinical Results
Topline results as of September 28, 2022 include:
Among 69 RANO-evaluable patients:
64% ORR and 91% clinical benefit rate (complete response + partial response/unconfirmed partial response + stable disease)
4% (n=3) confirmed complete responses
59% (n=41) partial responses (31 confirmed and 10 unconfirmed)
28% (n=19) patients with stable disease
86% (n=59) of patients had a BRAF fusion alteration, for which there are no approved systemic therapies, while the remaining 14% (n=10) had a BRAF mutation
Safety data, based on 77 treated patients, indicated monotherapy tovorafenib to be generally well-tolerated. The most common side effects reported related to tovorafenib were change in hair color (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%) and maculopapular rash (42%).
Among a total of 77 treated patients:
Participants were heavily pretreated, with a median of three prior lines of systemic therapy (range: 1-9)
The median duration of tovorafenib treatment was 8.4 months, with 77% (n=59) of patients on treatment at the time of the data cutoff
Nearly 60% (n=46) of patients had already received at least one prior MAPK inhibitor prior to study participation
Based on the data from the FIREFLY-1 trial, the Company plans an NDA submission in 1H2023.
Why This Data is Important
All cancers display genetic mutations which alter the homeostasis of the baseline non-cancerous cell, and transform it into a neoplastic cell. As molecular oncology has advanced, we have been able to catalog a number of important mutations, and in some cases, develop targeted drugs to attack the mutants. Tovorafenib is a highly-selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which may offer an important alternative for people with primary brain tumors or brain metastases of solid tumors.
Of utmost importance is that tovorafenib is brain-penetrant, which is necessary for medicines that are designed to directly act upon a target in brain cancer. While there are many excellent targeted drugs for non-brain cancers, few exist with adequate enough brain penetrance to allow therapeutic concentrations of the drug to reach the brain without also causing systemic toxicities.
Well Done, Day One Biopharmaceuticals!
Samuel Blackman, MD/PhD co-founded Day One (Nasdaq: DAWN) in 2018 with a focus on bringing new therapeutic options to pediatric cancer patients. The name Day One invokes the “Day One Talk” that families have upon learning of the life-altering diagnosis of cancer in a child. While children often do benefit from medicines developed in adult populations, there are specific challenges associated with pharmaceutical R&D in pediatric populations. Such challenges can delay the labeling of new drugs for pediatric populations, and have historically resulted in pediatric oncologists resorting to trial-and-error tinkering to determine proper dosing regimens and AE management in children.
For a company and its investors to go “All In” on pediatric cancer, it takes a special kind of motivation and tenacity.
“N-of-1 on Behalf of All”
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