- Overall response rate (ORR) of 64% and clinical benefit rate (CBR) of 91% in 69 heavily-pretreated, RANO-evaluable patients
- Median duration of 8.4 months on therapy as of
September 28, 2022 , with 77% of patients remaining on treatment - Additional data to be presented at a medical meeting in the second quarter of 2023
- New Drug Application submission planned for first half of 2023
The primary endpoint of the FIREFLY-1 trial is overall response rate (ORR) by Response Assessment for Neuro-Oncology (RANO) criteria as assessed by blinded independent central review. Topline results as of
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
“The responses we’ve observed in the FIREFLY-1 study with weekly monotherapy tovorafenib in children with recurrent or progressive low-grade gliomas are very encouraging,” said
FIREFLY-1 is evaluating tovorafenib as once-weekly monotherapy in patients aged 6 months to 25 years with recurrent or progressive pLGG. The trial is being conducted in collaboration with the
“Based on the efficacy and safety profile of tovorafenib observed to date from the FIREFLY-1 trial population, we plan to submit a New Drug Application in the first half of this year that will include additional follow up from the full study population,” said
In addition to FIREFLY-1, Day One is expanding the development of tovorafenib as a front-line therapy for patients newly diagnosed with pLGG. The global, Phase 3, registrational FIREFLY-2/LOGGIC clinical trial is evaluating once-weekly monotherapy tovorafenib in newly-diagnosed patients with pLGG harboring a known activating RAF alteration.
About Pediatric Low-Grade Glioma
Pediatric low-grade glioma (pLGG) is the most common brain tumor diagnosed in children, accounting for 30% – 50% of all central nervous system tumors. BRAF wild-type fusions are the most common cancer-causing genomic alterations in pediatric low-grade gliomas. These genomic alterations are also found in several adult and pediatric solid tumors.
Pediatric low-grade glioma can impact a child’s health in many ways depending on tumor size and location, including vision loss and motor dysfunction. There are no approved therapies for pLGG, and current treatment approaches are associated with potential acute and life-long adverse effects. While most children with pLGG survive their cancer, children who do not achieve remission following surgery may face years of increasingly aggressive therapies. Due to the indolent nature of pLGG, patients generally receive multiple years of systemic therapy.
About Tovorafenib
Tovorafenib is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway, which is being investigated in primary brain tumors or brain metastases of solid tumors. Tovorafenib has been studied in over 325 patients to date. Currently tovorafenib is under evaluation in a pivotal Phase 2 clinical trial (FIREFLY-1) among pediatric, adolescent and young adult patients with recurrent or progressive pLGG, which is an area of considerable unmet need with no approved therapies. Tovorafenib is also being evaluated alone or as a combination therapy for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway aberrations (FIRELIGHT-1).
Tovorafenib has been granted Breakthrough Therapy and Rare Pediatric Disease designations by the
About the
About
Day One partners with leading clinical oncologists, families, and scientists to identify, acquire, and develop important emerging cancer treatments. The Company’s lead product candidate, tovorafenib (DAY101), is an investigational, oral, brain-penetrant, highly-selective type II pan-RAF kinase inhibitor. The Company’s pipeline also includes pimasertib, an investigational, oral, highly-selective small molecule inhibitor of mitogen‐activated protein kinases 1 and 2 (MEK-1/-2). Day One is based in
Cautionary Note Regarding Forward-Looking Statements
This press release contains “forward-looking” statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: Day One’s plans to develop cancer therapies, expectations from current clinical trials, the execution of the Phase 2 and Phase 3 clinical trial for tovorafenib as designed, any expectations about safety, efficacy, timing and ability to complete clinical trials, release data results and to obtain regulatory approvals for tovorafenib and other candidates in development, and the ability of tovorafenib to treat pLGG or related indications.
Statements including words such as “believe,” “plan,” “continue,” “expect,” “will,” “develop,” “signal,” “potential,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements.
Forward-looking statements are subject to risks and uncertainties that may cause Day One’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the
DAY ONE MEDIA
laura.cooper@dayonebio.com
DAY ONE INVESTORS
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