This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the efficacy, safety, and tolerability of DAY101 monotherapy versus standard of care (SoC) chemotherapy in patients with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring front-line systemic therapy.
LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy
Approximately 400 treatment-naïve low-grade glioma patients will be randomized 1:1 to either DAY101 (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).
Arm 1 (DAY101): treatment cycles will repeat every 28 days in the absence of disease progression. Patients will continue DAY101 until any of the following occurs: radiographic progression based on Response Assessment in Neuro-Oncology (RANO) criteria as determined by the Investigator and confirmed by the Independent Review Committee (IRC), unacceptable toxicity, withdrawal of consent to treatment, or end of study.
Arm 2 (Investigator's Choice of SoC Chemotherapy): patients will receive one of 3 SoC chemotherapy options selected by the treating Investigator: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) regimen, International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) regimen, or vinblastine (VBL) regimen. The choice of SoC chemotherapy regimen will be selected prior to patient randomization. Treatment will continue until completion of therapy or until any of the following occurs: radiographic progression based on RANO criteria as determined by the Investigator and confirmed by the IRC, unacceptable toxicity, withdrawal of consent to treatment, or end of study.
During treatment phase, patients who demonstrate radiographic progression per RANO criteria as determined by the Investigator and confirmed by IRC in Arm 1 (DAY101) may be allowed to continue DAY101 if, in the opinion of the Investigator, the patient is deriving clinical benefit from continuing study treatment and approved by the Sponsor. Patients who demonstrate radiographic progression per RANO criteria as determined by the Investigator and confirmed by IRC during the treatment phase in Arm 2 (SoC chemotherapy) and discontinue treatment may be eligible to receive DAY101 at the same treatment and assessment schedule. In addition, Arm 2 patients who demonstrate radiographic progression after completion of chemotherapy [ie, during long-term follow-up (LTFU)] may be eligible to receive DAY101.