Day One Biopharmaceuticals announced new data from the registrational Phase 2 FIREFLY-1 trial evaluating the investigational agent tovorafenib (DAY101). These data were shared in an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. In addition, the Company announced that it has initiated a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for tovorafenib as a monotherapy in relapsed or progressive pediatric low-grade glioma (pLGG).

Updated FIREFLY-1 Data Presented at ASCO: FIREFLY-1, an open-label, pivotal Phase 2 trial, treated 77 patients and evaluated tovorafenib as a once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG (Arm 1). The primary endpoint of the FIREFLY-1 trial is overall response rate (ORR) by Response Assessment for Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria as assessed by blinded independent central review. Secondary endpoints include ORR by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG), progression-free survival (PFS), duration of response (DOR), time to response, clinical benefit rate and safety.

The study also includes an exploratory analysis of ORR by Response Assessment Neuro-Oncology Low-Grade Glioma (RANO-LGG). New data from the FIREFLY-1 trial, with a data cutoff of December 22, 2022, were presented at ASCO by Dr. Lindsay Kilburn of Children's National Medical Center. Patient demographics in registrational Arm 1 (n=77): 83% (n=64) of patients had a BRAF fusion, for which there are no approved systemic therapies, while the remaining 17% (n=13) had a BRAF V600E mutation.

Participants were heavily pretreated, with a median of two prior lines of systemic therapy (range: 1-9) and 49% (n=38) of patients having 3 or more prior lines of therapy. 60% (n=46) of patients had already received at least one prior MAPK inhibitor prior to study participation. RANO-HGG (n=69) data: 67% ORR by RANO-HGG, the primary endpoint of the trial; 93% clinical benefit rate (complete response (CR) + partial response (PR) + stable disease (SD)); 6% (n=4) CR; 61% (n=42) PR, including 3 uPR; 26% (n=18) SD; and At the time of data cutoff, the median duration of response (DOR) based on RANO-HGG criteria was not yet reached (95% CI: 9.0 months, not estimable).

Among a total of 77 treated patients: The median duration of tovorafenib treatment was 10.8 months, with 74% (n=57) of patients on treatment at the time of data cutoff. Safety data, based on the 136 patients treated in both Arm 1 and Arm 2 of FIREFLY-1, indicated monotherapy tovorafenib to be generally well-tolerated. The vast majority of adverse events were Grade 1 or Grade 2, with most common side effects reported related to tovorafenib being change in hair color (71%), fatigue (50%), vomiting (43%), maculopapular rash (41%) and headache (39%).

The most commonly reported lab abnormalities were CPK elevation, anemia, hypophosphatemia and AST elevation. Nearly all of the lab abnormalities had no clinical manifestations and did not require clinical intervention or change in study treatment. Additional Secondary and Exploratory Endpoint Analyses: The Company also shared the evaluation of responses by RAPNO-LGG and RANO-LGG.

Those results include: RAPNO-LGG data (n=69): 51% (n=35) ORR by RAPNO-LGG; 25% (n=17) PR including 4 uPR; 26% (n=18) MR including 4 uPR; and 36% (n=25) patients with SD. The median time to response was 5.5 months for confirmed responses. At the time of data cutoff, the median Independent Review Committee (IRC)-assessed DOR based on confirmed RAPNO-LGG responses is 12 months (95% CI: 11.2, not estimable) RANO-LGG (n=76) data: 49% (n=37) ORR by RANO-LGG; 26% (n= 20) PR including 8 uPR; 22% (n= 17) MR including 2 uMR; and 34% (n=26) patients with SD.

The median time to response was 4.2 months for confirmed responses. At the time of data cutoff, the median IRC-assessed DOR based on confirmed RANO-LGG responses is 14.4 months (95% CI: 8.4, not estimable).